Targeting viral entry as a strategy for broad-spectrum antivirals
Identifieur interne : 000949 ( Pmc/Corpus ); précédent : 000948; suivant : 000950Targeting viral entry as a strategy for broad-spectrum antivirals
Auteurs : Michela Mazzon ; Mark MarshSource :
- F1000Research [ 2046-1402 ] ; 2019.
Abstract
The process of entry into a host cell is a key step in the life cycle of most viruses. In recent years, there has been a significant increase in our understanding of the routes and mechanisms of entry for a number of these viruses. This has led to the development of novel broad-spectrum antiviral approaches that target host cell proteins and pathways, in addition to strategies focused on individual viruses or virus families. Here we consider a number of these approaches and their broad-spectrum potential.
Url:
DOI: 10.12688/f1000research.19694.1
PubMed: 31559009
PubMed Central: 6743247
Links to Exploration step
PMC:6743247Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Targeting viral entry as a strategy for broad-spectrum antivirals</title><author><name sortKey="Mazzon, Michela" sort="Mazzon, Michela" uniqKey="Mazzon M" first="Michela" last="Mazzon">Michela Mazzon</name><affiliation><nlm:aff id="a1">MRC Laboratory for Molecular Cell Biology, University College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Marsh, Mark" sort="Marsh, Mark" uniqKey="Marsh M" first="Mark" last="Marsh">Mark Marsh</name><affiliation><nlm:aff id="a1">MRC Laboratory for Molecular Cell Biology, University College London, London, UK</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31559009</idno><idno type="pmc">6743247</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743247</idno><idno type="RBID">PMC:6743247</idno><idno type="doi">10.12688/f1000research.19694.1</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000949</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000949</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Targeting viral entry as a strategy for broad-spectrum antivirals</title><author><name sortKey="Mazzon, Michela" sort="Mazzon, Michela" uniqKey="Mazzon M" first="Michela" last="Mazzon">Michela Mazzon</name><affiliation><nlm:aff id="a1">MRC Laboratory for Molecular Cell Biology, University College London, London, UK</nlm:aff></affiliation></author><author><name sortKey="Marsh, Mark" sort="Marsh, Mark" uniqKey="Marsh M" first="Mark" last="Marsh">Mark Marsh</name><affiliation><nlm:aff id="a1">MRC Laboratory for Molecular Cell Biology, University College London, London, UK</nlm:aff></affiliation></author></analytic><series><title level="j">F1000Research</title><idno type="eISSN">2046-1402</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The process of entry into a host cell is a key step in the life cycle of most viruses. In recent years, there has been a significant increase in our understanding of the routes and mechanisms of entry for a number of these viruses. This has led to the development of novel broad-spectrum antiviral approaches that target host cell proteins and pathways, in addition to strategies focused on individual viruses or virus families. Here we consider a number of these approaches and their broad-spectrum potential.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Marsh, M" uniqKey="Marsh M">M Marsh</name></author><author><name sortKey="Helenius, A" uniqKey="Helenius A">A Helenius</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mercer, J" uniqKey="Mercer J">J Mercer</name></author><author><name sortKey="Schelhaas, M" uniqKey="Schelhaas M">M Schelhaas</name></author><author><name sortKey="Helenius, A" uniqKey="Helenius A">A Helenius</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sanchez San Martin, C" uniqKey="Sanchez San Martin C">C Sánchez-San Martín</name></author><author><name sortKey="Liu, Cy" uniqKey="Liu C">CY Liu</name></author><author><name sortKey="Kielian, M" uniqKey="Kielian M">M Kielian</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mercer, J" uniqKey="Mercer J">J Mercer</name></author><author><name sortKey="Helenius, A" uniqKey="Helenius A">A Helenius</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Moller Tank, S" uniqKey="Moller Tank S">S Moller-Tank</name></author><author><name sortKey="Maury, W" uniqKey="Maury W">W Maury</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Saeed, Mf" uniqKey="Saeed M">MF Saeed</name></author><author><name sortKey="Kolokoltsov, Aa" uniqKey="Kolokoltsov A">AA Kolokoltsov</name></author><author><name sortKey="Albrecht, T" uniqKey="Albrecht T">T Albrecht</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wudunn, D" uniqKey="Wudunn D">D WuDunn</name></author><author><name sortKey="Spear, Pg" uniqKey="Spear P">PG Spear</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Giroglou, T" uniqKey="Giroglou T">T Giroglou</name></author><author><name sortKey="Florin, L" uniqKey="Florin L">L Florin</name></author><author><name sortKey="Sch Fer, F" uniqKey="Sch Fer F">F Schäfer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Feldman, Sa" uniqKey="Feldman S">SA Feldman</name></author><author><name sortKey="Hendry, Rm" uniqKey="Hendry R">RM Hendry</name></author><author><name sortKey="Beeler, Ja" uniqKey="Beeler J">JA Beeler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Klimyte, Em" uniqKey="Klimyte E">EM Klimyte</name></author><author><name sortKey="Smith, Se" uniqKey="Smith S">SE Smith</name></author><author><name sortKey="Oreste, P" uniqKey="Oreste P">P Oreste</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Collett, Ms" uniqKey="Collett M">MS Collett</name></author><author><name sortKey="Hincks, Jr" uniqKey="Hincks J">JR Hincks</name></author><author><name sortKey="Benschop, K" uniqKey="Benschop K">K Benschop</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ghosh, T" uniqKey="Ghosh T">T Ghosh</name></author><author><name sortKey="Chattopadhyay, K" uniqKey="Chattopadhyay K">K Chattopadhyay</name></author><author><name sortKey="Marschall, M" uniqKey="Marschall M">M Marschall</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, E" uniqKey="Lee E">E Lee</name></author><author><name sortKey="Pavy, M" uniqKey="Pavy M">M Pavy</name></author><author><name sortKey="Young, N" uniqKey="Young N">N Young</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cagno, V" uniqKey="Cagno V">V Cagno</name></author><author><name sortKey="Andreozzi, P" uniqKey="Andreozzi P">P Andreozzi</name></author><author><name sortKey="D Licarnasso, M" uniqKey="D Licarnasso M">M D’Alicarnasso</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Botos, I" uniqKey="Botos I">I Botos</name></author><author><name sortKey="Wlodawer, A" uniqKey="Wlodawer A">A Wlodawer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barrientos, Lg" uniqKey="Barrientos L">LG Barrientos</name></author><author><name sortKey="O Eefe, Br" uniqKey="O Eefe B">BR O’Keefe</name></author><author><name sortKey="Bray, M" uniqKey="Bray M">M Bray</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, Y" uniqKey="Zhou Y">Y Zhou</name></author><author><name sortKey="Simmons, G" uniqKey="Simmons G">G Simmons</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carette, Je" uniqKey="Carette J">JE Carette</name></author><author><name sortKey="Raaben, M" uniqKey="Raaben M">M Raaben</name></author><author><name sortKey="Wong, Ac" uniqKey="Wong A">AC Wong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Malakhov, Mp" uniqKey="Malakhov M">MP Malakhov</name></author><author><name sortKey="Aschenbrenner, Lm" uniqKey="Aschenbrenner L">LM Aschenbrenner</name></author><author><name sortKey="Smee, Df" uniqKey="Smee D">DF Smee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Moss, Rb" uniqKey="Moss R">RB Moss</name></author><author><name sortKey="Hansen, C" uniqKey="Hansen C">C Hansen</name></author><author><name sortKey="Sanders, Rl" uniqKey="Sanders R">RL Sanders</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, F" uniqKey="Li F">F Li</name></author><author><name sortKey="Ma, C" uniqKey="Ma C">C Ma</name></author><author><name sortKey="Wang, J" uniqKey="Wang J">J Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Macarthur, Rd" uniqKey="Macarthur R">RD MacArthur</name></author><author><name sortKey="Novak, Rm" uniqKey="Novak R">RM Novak</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dorr, P" uniqKey="Dorr P">P Dorr</name></author><author><name sortKey="Westby, M" uniqKey="Westby M">M Westby</name></author><author><name sortKey="Dobbs, S" uniqKey="Dobbs S">S Dobbs</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pastore, C" uniqKey="Pastore C">C Pastore</name></author><author><name sortKey="Ramos, A" uniqKey="Ramos A">A Ramos</name></author><author><name sortKey="Mosier, De" uniqKey="Mosier D">DE Mosier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vermeire, K" uniqKey="Vermeire K">K Vermeire</name></author><author><name sortKey="Bell, Tw" uniqKey="Bell T">TW Bell</name></author><author><name sortKey="Van Puyenbroeck, V" uniqKey="Van Puyenbroeck V">V van Puyenbroeck</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Dongen, Mjp" uniqKey="Van Dongen M">MJP van Dongen</name></author><author><name sortKey="Kadam, Ru" uniqKey="Kadam R">RU Kadam</name></author><author><name sortKey="Juraszek, J" uniqKey="Juraszek J">J Juraszek</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jae, Lt" uniqKey="Jae L">LT Jae</name></author><author><name sortKey="Raaben, M" uniqKey="Raaben M">M Raaben</name></author><author><name sortKey="Herbert, As" uniqKey="Herbert A">AS Herbert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wec, Az" uniqKey="Wec A">AZ Wec</name></author><author><name sortKey="Nyakatura, Ek" uniqKey="Nyakatura E">EK Nyakatura</name></author><author><name sortKey="Herbert, As" uniqKey="Herbert A">AS Herbert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fabozzi, G" uniqKey="Fabozzi G">G Fabozzi</name></author><author><name sortKey="Pegu, A" uniqKey="Pegu A">A Pegu</name></author><author><name sortKey="Koup, Ra" uniqKey="Koup R">RA Koup</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cote, M" uniqKey="Cote M">M Côté</name></author><author><name sortKey="Misasi, J" uniqKey="Misasi J">J Misasi</name></author><author><name sortKey="Ren, T" uniqKey="Ren T">T Ren</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Buontempo, Pj" uniqKey="Buontempo P">PJ Buontempo</name></author><author><name sortKey="Cox, S" uniqKey="Cox S">S Cox</name></author><author><name sortKey="Wright Minogue, J" uniqKey="Wright Minogue J">J Wright-Minogue</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Torres Torres, S" uniqKey="Torres Torres S">S Torres-Torres</name></author><author><name sortKey="Myers, Al" uniqKey="Myers A">AL Myers</name></author><author><name sortKey="Klatte, Jm" uniqKey="Klatte J">JM Klatte</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smith, Tj" uniqKey="Smith T">TJ Smith</name></author><author><name sortKey="Kremer, Mj" uniqKey="Kremer M">MJ Kremer</name></author><author><name sortKey="Luo, M" uniqKey="Luo M">M Luo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Abdelnabi, R" uniqKey="Abdelnabi R">R Abdelnabi</name></author><author><name sortKey="Geraets, Ja" uniqKey="Geraets J">JA Geraets</name></author><author><name sortKey="Ma, Y" uniqKey="Ma Y">Y Ma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sun, L" uniqKey="Sun L">L Sun</name></author><author><name sortKey="Lee, H" uniqKey="Lee H">H Lee</name></author><author><name sortKey="Thibaut, Hj" uniqKey="Thibaut H">HJ Thibaut</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Diehl, N" uniqKey="Diehl N">N Diehl</name></author><author><name sortKey="Schaal, H" uniqKey="Schaal H">H Schaal</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mazzon, M" uniqKey="Mazzon M">M Mazzon</name></author><author><name sortKey="Castro, C" uniqKey="Castro C">C Castro</name></author><author><name sortKey="Thaa, B" uniqKey="Thaa B">B Thaa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mercer, J" uniqKey="Mercer J">J Mercer</name></author><author><name sortKey="Knebel, S" uniqKey="Knebel S">S Knébel</name></author><author><name sortKey="Schmidt, Fi" uniqKey="Schmidt F">FI Schmidt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dutta, D" uniqKey="Dutta D">D Dutta</name></author><author><name sortKey="Williamson, Cd" uniqKey="Williamson C">CD Williamson</name></author><author><name sortKey="Cole, Nb" uniqKey="Cole N">NB Cole</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Macia, E" uniqKey="Macia E">E Macia</name></author><author><name sortKey="Ehrlich, M" uniqKey="Ehrlich M">M Ehrlich</name></author><author><name sortKey="Massol, R" uniqKey="Massol R">R Massol</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mccluskey, A" uniqKey="Mccluskey A">A McCluskey</name></author><author><name sortKey="Daniel, Ja" uniqKey="Daniel J">JA Daniel</name></author><author><name sortKey="Hadzic, G" uniqKey="Hadzic G">G Hadzic</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Harper, Cb" uniqKey="Harper C">CB Harper</name></author><author><name sortKey="Martin, S" uniqKey="Martin S">S Martin</name></author><author><name sortKey="Nguyen, Th" uniqKey="Nguyen T">TH Nguyen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Wilde, Ah" uniqKey="De Wilde A">AH de Wilde</name></author><author><name sortKey="Jochmans, D" uniqKey="Jochmans D">D Jochmans</name></author><author><name sortKey="Posthuma, Cc" uniqKey="Posthuma C">CC Posthuma</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Blaising, J" uniqKey="Blaising J">J Blaising</name></author><author><name sortKey="Levy, Pl" uniqKey="Levy P">PL Lévy</name></author><author><name sortKey="Polyak, Sj" uniqKey="Polyak S">SJ Polyak</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mazzon, M" uniqKey="Mazzon M">M Mazzon</name></author><author><name sortKey="Ortega Prieto, Am" uniqKey="Ortega Prieto A">AM Ortega-Prieto</name></author><author><name sortKey="Imrie, D" uniqKey="Imrie D">D Imrie</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Banbury, Dn" uniqKey="Banbury D">DN Banbury</name></author><author><name sortKey="Oakley, Jd" uniqKey="Oakley J">JD Oakley</name></author><author><name sortKey="Sessions, Rb" uniqKey="Sessions R">RB Sessions</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dejonghe, W" uniqKey="Dejonghe W">W Dejonghe</name></author><author><name sortKey="Kuenen, S" uniqKey="Kuenen S">S Kuenen</name></author><author><name sortKey="Mylle, E" uniqKey="Mylle E">E Mylle</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jurgeit, A" uniqKey="Jurgeit A">A Jurgeit</name></author><author><name sortKey="Mcdowell, R" uniqKey="Mcdowell R">R McDowell</name></author><author><name sortKey="Moese, S" uniqKey="Moese S">S Moese</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hayes, Wj" uniqKey="Hayes W">WJ HAYES</name></author><author><name sortKey="Laws, Jr" uniqKey="Laws J">JR LAWS</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Doms, Rw" uniqKey="Doms R">RW Doms</name></author><author><name sortKey="Moore, Jp" uniqKey="Moore J">JP Moore</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kaufmann, She" uniqKey="Kaufmann S">SHE Kaufmann</name></author><author><name sortKey="Dorhoi, A" uniqKey="Dorhoi A">A Dorhoi</name></author><author><name sortKey="Hotchkiss, Rs" uniqKey="Hotchkiss R">RS Hotchkiss</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Savarino, A" uniqKey="Savarino A">A Savarino</name></author><author><name sortKey="Boelaert, Jr" uniqKey="Boelaert J">JR Boelaert</name></author><author><name sortKey="Cassone, A" uniqKey="Cassone A">A Cassone</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Long, J" uniqKey="Long J">J Long</name></author><author><name sortKey="Wright, E" uniqKey="Wright E">E Wright</name></author><author><name sortKey="Molesti, E" uniqKey="Molesti E">E Molesti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nicholson, Kg" uniqKey="Nicholson K">KG Nicholson</name></author><author><name sortKey="Wiselka, Mj" uniqKey="Wiselka M">MJ Wiselka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Monto, As" uniqKey="Monto A">AS Monto</name></author><author><name sortKey="Arden, Nh" uniqKey="Arden N">NH Arden</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schornberg, K" uniqKey="Schornberg K">K Schornberg</name></author><author><name sortKey="Matsuyama, S" uniqKey="Matsuyama S">S Matsuyama</name></author><author><name sortKey="Kabsch, K" uniqKey="Kabsch K">K Kabsch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sakurai, Y" uniqKey="Sakurai Y">Y Sakurai</name></author><author><name sortKey="Kolokoltsov, Aa" uniqKey="Kolokoltsov A">AA Kolokoltsov</name></author><author><name sortKey="Chen, Cc" uniqKey="Chen C">CC Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xiao, Jh" uniqKey="Xiao J">JH Xiao</name></author><author><name sortKey="Rijal, P" uniqKey="Rijal P">P Rijal</name></author><author><name sortKey="Schimanski, L" uniqKey="Schimanski L">L Schimanski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Penny, Cj" uniqKey="Penny C">CJ Penny</name></author><author><name sortKey="Vassileva, K" uniqKey="Vassileva K">K Vassileva</name></author><author><name sortKey="Jha, A" uniqKey="Jha A">A Jha</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gunaratne, Gs" uniqKey="Gunaratne G">GS Gunaratne</name></author><author><name sortKey="Yang, Y" uniqKey="Yang Y">Y Yang</name></author><author><name sortKey="Li, F" uniqKey="Li F">F Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nelson, Ea" uniqKey="Nelson E">EA Nelson</name></author><author><name sortKey="Dyall, J" uniqKey="Dyall J">J Dyall</name></author><author><name sortKey="Hoenen, T" uniqKey="Hoenen T">T Hoenen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hover, S" uniqKey="Hover S">S Hover</name></author><author><name sortKey="King, B" uniqKey="King B">B King</name></author><author><name sortKey="Hall, B" uniqKey="Hall B">B Hall</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fung, Hb" uniqKey="Fung H">HB Fung</name></author><author><name sortKey="Guo, Y" uniqKey="Guo Y">Y Guo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Battles, Mb" uniqKey="Battles M">MB Battles</name></author><author><name sortKey="Langedijk, Jp" uniqKey="Langedijk J">JP Langedijk</name></author><author><name sortKey="Furmanova Hollenstein, P" uniqKey="Furmanova Hollenstein P">P Furmanova-Hollenstein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Roymans, D" uniqKey="Roymans D">D Roymans</name></author><author><name sortKey="Alnajjar, Ss" uniqKey="Alnajjar S">SS Alnajjar</name></author><author><name sortKey="Battles, Mb" uniqKey="Battles M">MB Battles</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mathieu, C" uniqKey="Mathieu C">C Mathieu</name></author><author><name sortKey="Huey, D" uniqKey="Huey D">D Huey</name></author><author><name sortKey="Jurgens, E" uniqKey="Jurgens E">E Jurgens</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Porotto, M" uniqKey="Porotto M">M Porotto</name></author><author><name sortKey="Rockx, B" uniqKey="Rockx B">B Rockx</name></author><author><name sortKey="Yokoyama, Cc" uniqKey="Yokoyama C">CC Yokoyama</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chao, Lh" uniqKey="Chao L">LH Chao</name></author><author><name sortKey="Jang, J" uniqKey="Jang J">J Jang</name></author><author><name sortKey="Johnson, A" uniqKey="Johnson A">A Johnson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schmidt, Ag" uniqKey="Schmidt A">AG Schmidt</name></author><author><name sortKey="Yang, Pl" uniqKey="Yang P">PL Yang</name></author><author><name sortKey="Harrison, Sc" uniqKey="Harrison S">SC Harrison</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stiasny, K" uniqKey="Stiasny K">K Stiasny</name></author><author><name sortKey="Heinz, Fx" uniqKey="Heinz F">FX Heinz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mcmahon, Ht" uniqKey="Mcmahon H">HT McMahon</name></author><author><name sortKey="Boucrot, E" uniqKey="Boucrot E">E Boucrot</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weston, S" uniqKey="Weston S">S Weston</name></author><author><name sortKey="Czieso, S" uniqKey="Czieso S">S Czieso</name></author><author><name sortKey="White, Ij" uniqKey="White I">IJ White</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Smith, S" uniqKey="Smith S">S Smith</name></author><author><name sortKey="Weston, S" uniqKey="Weston S">S Weston</name></author><author><name sortKey="Kellam, P" uniqKey="Kellam P">P Kellam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Buchrieser, J" uniqKey="Buchrieser J">J Buchrieser</name></author><author><name sortKey="Degrelle, Sa" uniqKey="Degrelle S">SA Degrelle</name></author><author><name sortKey="Couderc, T" uniqKey="Couderc T">T Couderc</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Johansen, Lm" uniqKey="Johansen L">LM Johansen</name></author><author><name sortKey="Brannan, Jm" uniqKey="Brannan J">JM Brannan</name></author><author><name sortKey="Delos, Se" uniqKey="Delos S">SE Delos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Salata, C" uniqKey="Salata C">C Salata</name></author><author><name sortKey="Baritussio, A" uniqKey="Baritussio A">A Baritussio</name></author><author><name sortKey="Munegato, D" uniqKey="Munegato D">D Munegato</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Turone, F" uniqKey="Turone F">F Turone</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Han, Y" uniqKey="Han Y">Y Han</name></author><author><name sortKey="Mesplede, T" uniqKey="Mesplede T">T Mesplède</name></author><author><name sortKey="Xu, H" uniqKey="Xu H">H Xu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vigant, F" uniqKey="Vigant F">F Vigant</name></author><author><name sortKey="Lee, J" uniqKey="Lee J">J Lee</name></author><author><name sortKey="Hollmann, A" uniqKey="Hollmann A">A Hollmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wolf, Mc" uniqKey="Wolf M">MC Wolf</name></author><author><name sortKey="Freiberg, An" uniqKey="Freiberg A">AN Freiberg</name></author><author><name sortKey="Zhang, T" uniqKey="Zhang T">T Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhu, Jd" uniqKey="Zhu J">JD Zhu</name></author><author><name sortKey="Meng, W" uniqKey="Meng W">W Meng</name></author><author><name sortKey="Wang, Xj" uniqKey="Wang X">XJ Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lu, Dy" uniqKey="Lu D">DY Lu</name></author><author><name sortKey="Wu, Hy" uniqKey="Wu H">HY Wu</name></author><author><name sortKey="Yarla, Ns" uniqKey="Yarla N">NS Yarla</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ford, N" uniqKey="Ford N">N Ford</name></author><author><name sortKey="Shubber, Z" uniqKey="Shubber Z">Z Shubber</name></author><author><name sortKey="Calmy, A" uniqKey="Calmy A">A Calmy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kirby, Bj" uniqKey="Kirby B">BJ Kirby</name></author><author><name sortKey="Symonds, Wt" uniqKey="Symonds W">WT Symonds</name></author><author><name sortKey="Kearney, Bp" uniqKey="Kearney B">BP Kearney</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bekerman, E" uniqKey="Bekerman E">E Bekerman</name></author><author><name sortKey="Einav, S" uniqKey="Einav S">S Einav</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cross, Rw" uniqKey="Cross R">RW Cross</name></author><author><name sortKey="Mire, Ce" uniqKey="Mire C">CE Mire</name></author><author><name sortKey="Feldmann, H" uniqKey="Feldmann H">H Feldmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De La Vega, Ma" uniqKey="De La Vega M">MA de La Vega</name></author><author><name sortKey="Caleo, G" uniqKey="Caleo G">G Caleo</name></author><author><name sortKey="Audet, J" uniqKey="Audet J">J Audet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thi, Ep" uniqKey="Thi E">EP Thi</name></author><author><name sortKey="Lee, Ach" uniqKey="Lee A">ACH Lee</name></author><author><name sortKey="Geisbert, Jb" uniqKey="Geisbert J">JB Geisbert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vaughn, Dw" uniqKey="Vaughn D">DW Vaughn</name></author><author><name sortKey="Green, S" uniqKey="Green S">S Green</name></author><author><name sortKey="Kalayanarooj, S" uniqKey="Kalayanarooj S">S Kalayanarooj</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dwek, Ra" uniqKey="Dwek R">RA Dwek</name></author><author><name sortKey="Butters, Td" uniqKey="Butters T">TD Butters</name></author><author><name sortKey="Platt, Fm" uniqKey="Platt F">FM Platt</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">F1000Res</journal-id><journal-id journal-id-type="iso-abbrev">F1000Res</journal-id><journal-id journal-id-type="pmc">F1000Research</journal-id><journal-title-group><journal-title>F1000Research</journal-title></journal-title-group><issn pub-type="epub">2046-1402</issn><publisher><publisher-name>F1000 Research Limited</publisher-name><publisher-loc>London, UK</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31559009</article-id><article-id pub-id-type="pmc">6743247</article-id><article-id pub-id-type="doi">10.12688/f1000research.19694.1</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group><subj-group><subject>Articles</subject></subj-group></article-categories><title-group><article-title>Targeting viral entry as a strategy for broad-spectrum antivirals</article-title><fn-group content-type="pub-status"><fn><p>[version 1; peer review: 3 approved]</p></fn></fn-group></title-group><contrib-group><contrib contrib-type="author"><name><surname>Mazzon</surname><given-names>Michela</given-names></name><role content-type="http://credit.casrai.org/">Conceptualization</role><role content-type="http://credit.casrai.org/">Writing – Original Draft Preparation</role><role content-type="http://credit.casrai.org/">Writing – Review & Editing</role><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2462-9925</contrib-id><xref ref-type="corresp" rid="c1">a</xref><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Marsh</surname><given-names>Mark</given-names></name><role content-type="http://credit.casrai.org/">Conceptualization</role><role content-type="http://credit.casrai.org/">Funding Acquisition</role><role content-type="http://credit.casrai.org/">Supervision</role><role content-type="http://credit.casrai.org/">Writing – Original Draft Preparation</role><role content-type="http://credit.casrai.org/">Writing – Review & Editing</role><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0213-3259</contrib-id><xref ref-type="corresp" rid="c2">b</xref><xref ref-type="aff" rid="a1">1</xref></contrib><aff id="a1"><label>1</label>MRC Laboratory for Molecular Cell Biology, University College London, London, UK</aff></contrib-group><author-notes><corresp id="c1"><label>a</label><email xlink:href="mailto:m.mazzon@ucl.ac.uk">m.mazzon@ucl.ac.uk</email></corresp><corresp id="c2"><label>b</label><email xlink:href="mailto:m.marsh@ucl.ac.uk">m.marsh@ucl.ac.uk</email></corresp><fn fn-type="COI-statement"><p>No competing interests were disclosed.</p></fn></author-notes><pub-date pub-type="epub"><day>12</day><month>9</month><year>2019</year></pub-date><pub-date pub-type="collection"><year>2019</year></pub-date><volume>8</volume><elocation-id>F1000 Faculty Rev-1628</elocation-id><history><date date-type="accepted"><day>30</day><month>8</month><year>2019</year></date></history><permissions><copyright-statement>Copyright: © 2019 Mazzon M and Marsh M</copyright-statement><copyright-year>2019</copyright-year><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="f1000research-8-21600.pdf"></self-uri><abstract><p>The process of entry into a host cell is a key step in the life cycle of most viruses. In recent years, there has been a significant increase in our understanding of the routes and mechanisms of entry for a number of these viruses. This has led to the development of novel broad-spectrum antiviral approaches that target host cell proteins and pathways, in addition to strategies focused on individual viruses or virus families. Here we consider a number of these approaches and their broad-spectrum potential.</p></abstract><kwd-group kwd-group-type="author"><kwd>Antiviral</kwd><kwd>Virus entry</kwd><kwd>Endocytosis</kwd><kwd>Virus fusion</kwd><kwd>Broad-spectrum</kwd><kwd>Host-targeted</kwd></kwd-group><funding-group><award-group id="fund-1"><funding-source>Medical Research Council</funding-source><award-id>MC_UU_12018/1</award-id></award-group><funding-statement>The authors are supported by Medical Research Council funding to the MRC-UCL LMCB University Unit (MC_UU_12018/1).</funding-statement><funding-statement><italic>The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</italic></funding-statement></funding-group></article-meta><notes><sec sec-type="editor-note"><title>Editorial Note on the Review Process</title><p><ext-link ext-link-type="uri" xlink:href="http://f1000research.com/browse/f1000-faculty-reviews">F1000 Faculty Reviews</ext-link> are commissioned from members of the prestigious
<ext-link ext-link-type="uri" xlink:href="http://f1000.com/prime/thefaculty">F1000 Faculty</ext-link> and are edited as a service to readers. In order to make these reviews as comprehensive and accessible as possible, the referees provide input before publication and only the final, revised version is published. The referees who approved the final version are listed with their names and affiliations but without their reports on earlier versions (any comments will already have been addressed in the published version).</p><p>The referees who approved this article are: </p><list list-type="simple" list-content="reviewer-list"><list-item><p><named-content content-type="reviewer-name">Priscilla L Yang</named-content>, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, USA
<fn fn-type="COI-statement"><p>No competing interests were disclosed.</p></fn></p></list-item><list-item><p><named-content content-type="reviewer-name">Graham Simmons</named-content>, Department of Pathology and Laboratory Medicine, University of California, San Francisco , California, USA
<fn fn-type="COI-statement"><p>No competing interests were disclosed.</p></fn></p></list-item><list-item><p><named-content content-type="reviewer-name">Jun Wang</named-content>, Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tuscon, USA
<fn fn-type="COI-statement"><p>No competing interests were disclosed.</p></fn></p></list-item></list></sec></notes></front><body><sec sec-type="intro"><title>Introduction</title><p>Although not a guarantee of successful infection, entry into a host cell is a critical stage in the life of a virus
<sup><xref rid="ref-1" ref-type="bibr">1</xref>,
<xref rid="ref-2" ref-type="bibr">2</xref></sup>. Once inside a cell, a virus still needs to overcome a hostile environment, evade immune responses, and subvert a range of cellular proteins and pathways to facilitate its replication. However, finding a permissive cell and delivering genetic information into its cytoplasm, and in some cases nucleus, is the first necessary step for viral infection. This has at least two important implications from a prophylactic and/or therapeutic perspective. The first is that blocking viral entry stops infection early on, preventing viral replication. The second is that because many viruses exploit cellular endocytic mechanisms to initiate internalization and infection, and cells have just a few such mechanisms, inhibiting these pathways may affect many different viruses, greatly expanding our currently limited antiviral portfolio.</p><p>It is now well established that, after initial attachment to the cell surface, many viruses, both enveloped and non-enveloped, exploit changes in environmental conditions, such as pH, interaction with a cellular receptor, or the activity of proteolytic enzymes, to trigger conformational changes in key proteins that mediate cell membrane penetration
<sup><xref rid="ref-1" ref-type="bibr">1</xref>–
<xref rid="ref-3" ref-type="bibr">3</xref></sup>. For enveloped viruses, the virus lipid bilayer needs to fuse with the cellular limiting membrane (either the plasma membrane or the membrane of endocytic organelles) to release the viral genome, and this is mediated by viral envelope proteins. For non-enveloped viruses, genome release is affected by viral capsid proteins that trigger cell membrane penetration and genome release.</p><p>While some viruses fuse directly at the plasma membrane, the majority use endocytic mechanisms to reach intracellular compartments, with clathrin-mediated endocytosis (CME), caveolin-mediated endocytosis, macropinocytosis, and phagocytosis currently being the best characterized of these pathways. CME in particular is exploited by numerous viruses, including alphaviruses, flaviviruses, orthomyxoviruses, and rhabdoviruses
<sup><xref rid="ref-1" ref-type="bibr">1</xref>,
<xref rid="ref-2" ref-type="bibr">2</xref></sup>, while macropinocytosis is linked to the uptake of larger viruses, such as poxviruses and filoviruses, that do not fit into clathrin-coated vesicles
<sup><xref rid="ref-4" ref-type="bibr">4</xref>–
<xref rid="ref-6" ref-type="bibr">6</xref></sup>. Thus, inhibiting these pathways might be expected to impact on a range of different viruses.</p><p>In this review, we summarize the main therapeutic approaches that target different stages of viral entry (
<xref ref-type="fig" rid="f1">Figure 1</xref>), either by inhibiting virus-specific interactions or by blocking conserved cellular mechanisms that viruses exploit to enter cells. This latter tactic is indicative of a change of focus for viral therapeutics, combining more traditional approaches directed at specific viruses with novel cell-targeted strategies with broad-spectrum potential.</p><fig fig-type="figure" id="f1" orientation="portrait" position="anchor"><label>Figure 1. </label><caption><title>Schematic representing the main stages of viral entry.</title><p>Processes inhibited by the antivirals described (attachment, receptor binding, endocytosis, trafficking, endosomal acidification, and fusion) are indicated.</p></caption><graphic xlink:href="f1000research-8-21600-g0000"></graphic></fig></sec><sec><title>Inhibition of cell adhesion</title><p>The first step in viral entry is virus adhesion to the cell surface. Regardless of the requirement to engage specific receptors, viruses often use non-specific electrostatic interactions with negatively charged sugars to attach to a cell surface until they encounter a specific entry receptor. Negatively charged heparan sulfate proteoglycans (HSPGs) are expressed on the surface of most eukaryotic cells and have been shown to be required for the binding of many viruses, including human immunodeficiency virus (HIV), herpes simplex virus (HSV), human cytomegalovirus (HCMV), human papilloma virus (HPV), respiratory syncytial virus (RSV), and flaviviruses
<sup><xref rid="ref-7" ref-type="bibr">7</xref>–
<xref rid="ref-10" ref-type="bibr">10</xref></sup>. Inhibition of these interactions through the development of “decoy” particles mimicking these molecules (heparin, sulfated polysaccharides, or sulfonic acid-coated nanoparticle) can effectively prevent infection
<italic>in vitro</italic>. However, limited efficacy is seen
<italic>in vivo</italic>, possibly owing to the poor bioavailability of these formulations. While high-molecular-weight molecules with a high degree of sulfation have the highest antiviral activity
<italic>in vitro</italic>, these compounds tend to bind to plasma proteins and have poor bioavailability
<sup><xref rid="ref-11" ref-type="bibr">11</xref>,
<xref rid="ref-12" ref-type="bibr">12</xref></sup>. Conversely, low-molecular-weight compounds have better bioavailability and are more effective
<italic>in vivo</italic><sup><xref rid="ref-13" ref-type="bibr">13</xref></sup> but are also associated with higher cytotoxicity, possibly owing to detergent effects on cellular membranes.</p><p>Virucidal activity may also be required to increase
<italic>in vivo</italic> efficacy. Cagno
<italic>et al</italic>. have shown that nanoparticles carrying long, flexible linkers mimicking HSPGs can simultaneously bind multiple sites on a virus and cause permanent distortion of the virion structure. This virucidal activity was sufficient to inhibit RSV infection in mice, suggesting that particles mimicking the negatively charged cellular surfaces to which viruses bind have the potential to be effective antivirals, as long as they include the capacity to inactivate viral infectivity
<sup><xref rid="ref-14" ref-type="bibr">14</xref></sup>.</p><p>It is important to note that sulfated polysaccharides are also known to have anticoagulant activity, but derivatives exist that do not show these properties
<italic>in vivo</italic> at therapeutic doses (e.g. fucoidan, galactan, and xylomannan)
<sup><xref rid="ref-12" ref-type="bibr">12</xref></sup>.</p><p>Other molecules that target common cellular components also have the potential to interfere with attachment and to have broad-spectrum antiviral activity. Cyanovirin-N is a naturally occurring lectin that has been shown to inhibit the attachment of HIV
<sup><xref rid="ref-15" ref-type="bibr">15</xref></sup> and Ebola virus (EBOV) to cells
<sup><xref rid="ref-16" ref-type="bibr">16</xref></sup>, most likely by binding to high-mannose oligosaccharides on the viral glycoproteins. The same mode of action may prevent infection by other viruses, though this remains to be tested, as does
<italic>in vivo</italic> efficacy
<italic>.</italic></p></sec><sec><title>Inhibition of receptor binding</title><sec><title>Cell surface receptors</title><p>While often involved in virus adhesion to cell surfaces, negatively charged sugars associated with cell surface glycoproteins and glycolipids can also act as virus receptors (e.g. sialic acid for influenza) or enable an interaction of sufficient strength to allow internalization of a virus by endocytosis, as may be the case for flaviviruses and filoviruses
<sup><xref rid="ref-17" ref-type="bibr">17</xref>,
<xref rid="ref-18" ref-type="bibr">18</xref></sup>. Both virus- and cell-targeted approaches have been studied to prevent the interaction between influenza hemagglutinin (HA) and sialic acids (SA) on glycoprotein and glycolipid receptors. Virus-targeted strategies include the use of protease inhibitors that block the processing of HA and peptides or small molecules that interfere with HA binding to SA. The most promising cell-targeted strategy is the attachment inhibitor DAS181, a recombinant protein made of a sialidase catalytic domain (which removes SA from influenza receptors) and a mucosal cell-surface anchoring sequence. This compound, highly potent
<italic>in vitro</italic> (IC
<sub>50</sub> between 0.04 and 0.9 nM), has been shown to be non-toxic to cells and to be effective
<italic>in vivo</italic> when administered pre- and post-exposure
<sup><xref rid="ref-19" ref-type="bibr">19</xref></sup>. A phase II trial showed reduction of viral load over 5 days’ administration at 10 mg/kg/day
<sup><xref rid="ref-20" ref-type="bibr">20</xref></sup>, and phase III trials are ongoing. A comprehensive overview of inhibitors of HA–SA interaction is presented by
<sup><xref rid="ref-12" ref-type="bibr">12</xref>,
<xref rid="ref-21" ref-type="bibr">21</xref></sup>.</p><p>For other cell-surface virus receptors, maraviroc (FDA approved in 2007) is currently the only drug that inhibits viral entry. Its target is CCR5, the major co-receptor required for HIV infection of CD4-positive cells
<sup><xref rid="ref-22" ref-type="bibr">22</xref></sup>. Maraviroc was developed by Pfizer through screening of their compound library and subsequent additional screens to improve activity and pharmacological properties of the initial hit compound. In combination with at least two additional anti-retroviral drugs, maraviroc is currently used in HIV-infected patients showing resistance to other compounds
<sup><xref rid="ref-23" ref-type="bibr">23</xref></sup>. While some limited development of resistance has been observed, the frequency of this is not clear
<sup><xref rid="ref-22" ref-type="bibr">22</xref></sup> and is usually associated with multiple mutations in the HIV envelope protein that generally cause a significant decrease in viral fitness
<sup><xref rid="ref-24" ref-type="bibr">24</xref></sup>. This notion, that viral adaptations to overcome inhibitors acting through cellular targets can weaken the virus, is a potentially significant and interesting advantage of host-targeted antiviral strategies.</p><p>An alternative tactic is to inhibit the synthesis of cellular membrane glycoproteins that function as receptors for specific viruses. Cyclotriazadisulfonamide (CADA), a small-molecule inhibitor of HIV replication, has been found to specifically inhibit the synthesis of the HIV receptor CD4 by binding to the protein signal sequence in the Sec61 translocon during the co-translational insertion of the nascent protein into the ER membrane
<sup><xref rid="ref-25" ref-type="bibr">25</xref></sup>. Decreased levels of CD4 render potential host cells refractory to HIV-1 infection and presumably HIV-2, HHV6, and any other viruses that use CD4 as a receptor. Whether this approach is effective
<italic>in vivo</italic> and whether it can be developed to inhibit the synthesis of a broader range of virus receptors remains to be seen (see
<xref rid="ref-25" ref-type="bibr">25</xref> for a discussion of evidence for other compounds that inhibit the synthesis of specific cell-surface proteins).</p><p>Inhibiting the interaction of a virus with target cells is also one of the main modes of action of antibodies, and the identification and generation of such antibodies remain major strategies for antiviral immunotherapies. The development of small molecules that mimic the effect of antibodies and can be administered orally also has potential. Scientists from Janssen developed such an approach starting from the identification of a broadly neutralizing antibody, bnAbCR6261, that targets a conserved region in the stem of influenza HA. They then used a displacement screening strategy to identify small molecules that could bind to the same region as the antibody. Further medicinal chemistry on the most promising hit led to compound JNJ4796, a benzylpiperazine derivative able to inhibit influenza infection in 3D cultures of human bronchial epithelial cells and in a mouse model. Encouragingly, protection from lethal challenge was seen after oral administration in this latter model
<sup><xref rid="ref-26" ref-type="bibr">26</xref></sup>.</p></sec><sec><title>Intracellular receptors</title><p>While most virus receptors are found at the cell surface, some viruses also interact with receptors inside endo-lysosomal compartments following their endocytosis. For example, EBOV uses the lysosomal protein Niemann Pick C-1 (NPC-1)
<sup><xref rid="ref-18" ref-type="bibr">18</xref></sup>, while Lassa fever virus has been shown to interact with LAMP1, another lysosomal protein
<sup><xref rid="ref-27" ref-type="bibr">27</xref></sup>. Antibody targeting of these interactions is complicated by the intracellular localization of the receptors. However, an exciting technology that has recently been expanded to viral infection is the development of bispecific antibodies. By linking the variable regions of an antibody recognizing the EBOV glycoprotein (GP) glycan cap (FV-M09) with the variable regions of antibodies recognizing either NPC-1 (mAb-548) or the NPC-1 binding region on GP (MR72), Wec
<italic>et al</italic>. showed that this bispecific antibody bound to EBOV is internalized into endo-lysosomal compartments where it potently blocks Ebola interaction with its intracellular receptor
<sup><xref rid="ref-28" ref-type="bibr">28</xref></sup>. This strategy, already tested for HIV
<sup><xref rid="ref-29" ref-type="bibr">29</xref></sup>, has been shown to protect mice, even when administered 2 days after challenge with EBOV
<sup><xref rid="ref-28" ref-type="bibr">28</xref></sup>.</p><p>Small-molecule inhibitors of NPC-1 that accumulate in endosomal compartments like U18666A
<sup><xref rid="ref-18" ref-type="bibr">18</xref></sup> and the piperazine-derivative 3.47
<sup><xref rid="ref-30" ref-type="bibr">30</xref></sup> also effectively block EBOV infection
<italic>in vitro</italic>, the first by inducing cholesterol accumulation in the lysosomes and the latter by directly interacting with NPC-1.</p></sec><sec><title>Non-enveloped viruses</title><p>Compounds also have been developed that selectively bind to non-enveloped virus capsid proteins to prevent interaction with cellular receptors or uncoating. One example is the enterovirus capsid inhibitor pocapavir
<sup><xref rid="ref-31" ref-type="bibr">31</xref></sup>, which has been tested as an investigational drug to treat neonatal viral sepsis
<sup><xref rid="ref-32" ref-type="bibr">32</xref></sup> and has also been trialed against the spread of attenuated poliovirus from vaccinated individuals
<sup><xref rid="ref-11" ref-type="bibr">11</xref></sup>. Pocapavir and other capsid binders fit into a hydrophobic pocket in the viral particle, preventing conformational changes required for uncoating
<sup><xref rid="ref-33" ref-type="bibr">33</xref></sup>, but have the disadvantage of selecting for drug-resistant mutants. More recently, a conserved VP1–VP3 interprotomer interface in the viral capsid, critical for the conformational changes necessary for RNA release, has been proposed as an alternative druggable target. Compounds binding to this interface have been shown to be active against a larger number of enteroviruses and also against rhinoviruses, though their ability to induce resistant variants has yet to be investigated
<sup><xref rid="ref-34" ref-type="bibr">34</xref></sup>. Tryptophan dendrimers that target the 5-fold-axis of the enterovirus-A71 capsid have also been shown to have antiviral potential
<italic>in vitro</italic> by preventing virus interaction with the (co-)receptors PSGL1 and heparan sulfate
<sup><xref rid="ref-35" ref-type="bibr">35</xref></sup>.
<bold></bold></p></sec></sec><sec><title>Inhibition of internalization</title><p>For viruses that do not penetrate directly at the plasma membrane, endocytosis is an essential step in the entry process. Endocytosis can be blocked by compounds that interfere with signaling cascades necessary to activate endocytosis or that inhibit the endocytosis machinery directly. The PI3K-AKT signaling pathway, for instance, has been shown to be required by a variety of viruses
<sup><xref rid="ref-36" ref-type="bibr">36</xref>,
<xref rid="ref-37" ref-type="bibr">37</xref></sup>, and its inhibition can prevent infection
<italic>in vitro</italic><sup><xref rid="ref-6" ref-type="bibr">6</xref></sup>. Similarly, vaccinia virus (VV) entry requires signaling through epidermal growth factor receptors (EGFR), serine/threonine kinases, protein kinase C, and p21-activated kinase 1 in addition to PI3K, and entry of at least some VV strains is sensitive to the tyrosine kinase inhibitor Genistein
<sup><xref rid="ref-38" ref-type="bibr">38</xref></sup>. However, studies of their effectiveness
<italic>in vivo</italic> are limited. While there is evidence that preventing PI3K/AKT activation reduces pathogenesis in mice infected with the alphavirus Ross River, this is likely to be due to post-entry effects on virus replication and cellular metabolism
<sup><xref rid="ref-37" ref-type="bibr">37</xref></sup>.</p><p>A number of research compounds exist that block endocytosis directly, including PitStop, which inhibits the formation of clathrin-coated pits
<sup><xref rid="ref-39" ref-type="bibr">39</xref></sup>, as well as Dynasore
<sup><xref rid="ref-40" ref-type="bibr">40</xref></sup> and the more potent derivative Dyngo-4a
<sup><xref rid="ref-41" ref-type="bibr">41</xref></sup>, which interfere with dynamin. While these compounds have been shown to inhibit the entry of various viruses
<italic>in vitro</italic>, they have not been used therapeutically as antivirals. A study by Harper
<italic>et al</italic>. showed that Dyngo-4a can inhibit botulinum neurotoxin type A endocytosis in neurons
<italic>in vitro</italic>; however,
<italic>in vivo</italic> administration only delayed the onset of symptoms by ~3 hours in 60% of infected mice. Encouragingly, animals treated with Dyngo-4a did not show signs of toxicity at the concentrations tested
<sup><xref rid="ref-42" ref-type="bibr">42</xref></sup>. Whether higher concentrations are required to see a stronger effect
<italic>in vivo,</italic> whether these have higher toxicity (because of either inhibition of endocytosis or off-target effects), and whether virus infection is affected requires further investigation. Several other compounds including chlorpromazine, chloroquine, and Arbidol have also been shown to inhibit endocytosis and have an antiviral effect
<italic>in vitro</italic><sup><xref rid="ref-43" ref-type="bibr">43</xref>,
<xref rid="ref-44" ref-type="bibr">44</xref></sup>, but efficacy
<italic>in vivo</italic> has not yet been reported.</p><p>In a recent study, starting from phenotypic screening with representatives of different virus families, we identified two compounds, niclosamide and Tyrphostin A9, with very broad-spectrum antiviral activity, affecting different stages of virus replication, including endocytosis
<sup><xref rid="ref-45" ref-type="bibr">45</xref></sup>. The most likely mode of action is through dissipation of proton gradients and inhibition of ATP synthesis
<sup><xref rid="ref-46" ref-type="bibr">46</xref>–
<xref rid="ref-48" ref-type="bibr">48</xref></sup>, which impact on multiple cellular pathways. However, using endocytosis assays, we were able to show that CME of the alphavirus Semliki Forest virus and of fluorescently labeled transferrin was significantly reduced by both compounds
<sup><xref rid="ref-45" ref-type="bibr">45</xref></sup>. While the pharmacokinetic properties of niclosamide prevent its accumulation in the blood
<sup><xref rid="ref-49" ref-type="bibr">49</xref></sup>, Tyrphostin A9 had a better profile and showed some ability to inhibit Zika virus infection in a mouse model
<sup><xref rid="ref-45" ref-type="bibr">45</xref></sup>. Tyrphostin A9 is also a general tyrosine kinase inhibitor and is likely to affect a variety of kinases involved in viral life cycles. Interestingly, Tyrphostin A23 has also been shown to inhibit CME by preventing the interaction between receptor tyrosine-based endocytic signals and the mu2 subunit of the AP-2 adaptor complex
<sup><xref rid="ref-46" ref-type="bibr">46</xref></sup>. Although the chemical properties of Tyrphostin A9 make it unlikely to become a drug, this work provided proof of concept that entry inhibitors with broad-spectrum antiviral activity
<italic>in vitro</italic> can also exhibit antiviral activity
<italic>in vivo</italic>.</p></sec><sec><title>Inhibition of fusion</title><p>For enveloped viruses, fusion is the next necessary step that allows a virus to release its genome into the cytoplasm. Fusion is mediated by virally encoded envelope glycoproteins displayed on the virion surface. Viruses require cellular cues to induce conformational changes in these envelope glycoproteins to initiate fusion with cellular membranes, in some cases the plasma membrane, and, for many viruses, endosomal membranes. For some viruses that fuse at the cell surface, such as HIV, receptor engagement provides the cue that initiates the envelope glycoprotein conformational changes and fusion
<sup><xref rid="ref-50" ref-type="bibr">50</xref></sup>. But for many viruses a common cue is the acidic pH of endosomal environments
<sup><xref rid="ref-1" ref-type="bibr">1</xref>,
<xref rid="ref-3" ref-type="bibr">3</xref>,
<xref rid="ref-51" ref-type="bibr">51</xref></sup>. Weak bases, including the antimalarial drug chloroquine, and carboxylic ionophores such as monensin, can inhibit endosomal acidification and block infection by a wide range of viruses
<italic>in vitro</italic><sup><xref rid="ref-1" ref-type="bibr">1</xref>,
<xref rid="ref-52" ref-type="bibr">52</xref>,
<xref rid="ref-53" ref-type="bibr">53</xref></sup>, but, with the exception of amantadine, few studies have tested their efficacy
<italic>in vivo.</italic> The weak base amantadine and some amantadine analogues have been used against influenza virus infection
<sup><xref rid="ref-54" ref-type="bibr">54</xref></sup>, but their activity is directed through inhibition of the viral M2 protein, rather than inhibition of endosomal acidification, and viruses rapidly evolve resistance
<sup><xref rid="ref-55" ref-type="bibr">55</xref></sup>.</p><p>An alternative cue to low pH is proteolytic cleavage of envelope proteins by endosomal proteases, as used by filoviruses, such as EBOV, and coronaviruses. For EBOV, proteolytic cleavage by endo-lysosomal cathepsins is essential to generate a form of the envelope glycoprotein that can bind NPC-1
<sup><xref rid="ref-56" ref-type="bibr">56</xref></sup>, and inhibitors of these proteases can effectively abrogate EBOV infection, although none of these compounds is currently approved for use in humans and selectivity remains an issue. Recently, a role for the two-pore calcium channel 2 (TPC2) in EBOV infection was shown. While the exact role of TPC2 is not yet clear, it is likely to control cues in the endo-lysosomal environment necessary for EBOV fusion
<sup><xref rid="ref-57" ref-type="bibr">57</xref></sup>. Interestingly, small molecules that target TPC2 inhibit EBOV infection both
<italic>in vitro</italic> and
<italic>in vivo</italic><sup><xref rid="ref-57" ref-type="bibr">57</xref>–
<xref rid="ref-59" ref-type="bibr">59</xref></sup>. These TPC2 antagonists, including tetrandrine, also inhibit MERS coronaviruses
<sup><xref rid="ref-60" ref-type="bibr">60</xref></sup>. Similarly, apilimod, a compound that targets a phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) involved in endosomal trafficking, also inhibits EBOV infection by blocking the transport of Ebola particles into NPC-1-containing endo-lysosomes
<sup><xref rid="ref-61" ref-type="bibr">61</xref></sup>. Whether these compounds act on other viruses that penetrate from late endosomes remains unclear. Elevation of endosomal potassium may also provide cues that activate the fusion proteins of some bunyaviruses and influenza viruses, and infection can be restricted by compounds that inhibit endosomal potassium channels
<sup><xref rid="ref-62" ref-type="bibr">62</xref></sup>. Together, these studies indicate that combining perturbants of the endocytic system might offer an effective approach to inhibiting a range of different viruses.</p><p>Some virus-specific fusion inhibitors also exist. Enfuvirtide, used in combination with other anti-retroviral therapies for the treatment of HIV, is a peptide that binds the heptad repeat region 2 in the gp41 subunit of the HIV envelope glycoprotein and prevents formation of the so-called stable six-helix bundle that is crucial for membrane fusion
<sup><xref rid="ref-63" ref-type="bibr">63</xref></sup>. Fusion inhibitors that stabilize metastable conformations of the RSV fusion protein have also been developed
<sup><xref rid="ref-64" ref-type="bibr">64</xref>,
<xref rid="ref-65" ref-type="bibr">65</xref></sup>. Though none of these is currently approved for use, a number are in clinical trials. Peptides that block the fusion of other paramyxoviruses, including measles, Nipah, and Hendra viruses, by interfering with the viral envelope proteins have also been developed and shown to have antiviral activity
<italic>in vivo</italic><sup><xref rid="ref-57" ref-type="bibr">57</xref>,
<xref rid="ref-66" ref-type="bibr">66</xref>,
<xref rid="ref-67" ref-type="bibr">67</xref></sup>. A similar approach using peptides or small molecules has also shown promise against flaviviruses (West Nile and dengue viruses)
<sup><xref rid="ref-68" ref-type="bibr">68</xref>,
<xref rid="ref-69" ref-type="bibr">69</xref></sup>.</p><p>An alternative approach to inhibiting fusion is to interfere with the biophysical properties of membranes through compounds that intercalate into cellular membranes and in so doing alter their rigidity or curvature. This can be achieved with certain lipids in tissue culture systems
<sup><xref rid="ref-70" ref-type="bibr">70</xref>,
<xref rid="ref-71" ref-type="bibr">71</xref></sup>. A similar effect may underlie the action of cellular proteins called interferon-inducible transmembrane proteins (IFITMs). Although the exact mode of action of these proteins (three in humans, IFITM 1–3) remains unclear, their effectiveness against an extraordinary variety of viruses suggests that interfering with the composition/biophysical properties of cellular membranes involved in virus entry can be a potent broad-spectrum antiviral strategy
<sup><xref rid="ref-64" ref-type="bibr">64</xref>,
<xref rid="ref-72" ref-type="bibr">72</xref>,
<xref rid="ref-73" ref-type="bibr">73</xref></sup>. However, recent work by Buchrieser
<italic>et al</italic>. indicates that IFITM expression can interfere with placental development by inhibiting syncytin-mediated syncytiotrophoblast formation, indicating that these proteins can interfere in cellular fusion reactions
<sup><xref rid="ref-74" ref-type="bibr">74</xref></sup>. Whether they impact on other cell–cell fusion events or intracellular membrane fusion processes remains to be established.</p><p>Using phenotypic screens, we and others have identified a number of compounds that, because of their biophysical properties, are likely to intercalate into the endosomal membranes and prevent fusion
<sup><xref rid="ref-45" ref-type="bibr">45</xref>,
<xref rid="ref-75" ref-type="bibr">75</xref></sup>. This is possibly the mode of action of selective estrogen receptor modulators (SERMs) and similar amphipathic compounds, including amiodarone
<sup><xref rid="ref-76" ref-type="bibr">76</xref>,
<xref rid="ref-77" ref-type="bibr">77</xref></sup> and amodiaquine
<sup><xref rid="ref-78" ref-type="bibr">78</xref></sup>, although it is possible that these compounds may also alter endosomal pH. However, the concentrations required to achieve similar antiviral effects
<italic>in vivo</italic> are likely to be high, and the risk of side effects significant.</p><p>Interfering with viral rather than cellular membranes is also a promising broad-spectrum antiviral approach for enveloped viruses. LJ001 is a small molecule which oxidizes the unsaturated phospholipids of both cellular and viral membranes
<sup><xref rid="ref-79" ref-type="bibr">79</xref></sup>. This is likely to alter membrane curvature and fluidity, preventing fusion. Interestingly, while affecting both cellular and viral membranes, only the latter are significantly affected, most likely because the cellular membrane can rapidly replace damaged lipids, a property that viruses do not share
<sup><xref rid="ref-80" ref-type="bibr">80</xref></sup>. This makes LJ001 effective
<italic>in vitro</italic> against a wide variety of viruses including influenza, and with very limited toxicity. Unfortunately, little effectiveness was seen
<italic>in vivo</italic>, owing to a short half-life (~4 hours) and low concentration of the compound in serum. Furthermore, LJ001 needs light to activate, which limits its application
<italic>in vivo</italic>. Nevertheless, analogues with improved stability and pharmacokinetics are being developed
<sup><xref rid="ref-79" ref-type="bibr">79</xref></sup>.</p></sec><sec><title>Conclusions and future outlook</title><p>Host cell entry is a crucial step for most viruses, and preventing entry provides a clear early opportunity to control infection. As viruses use just a few conserved cellular pathways for entry, targeting cellular proteins rather than viral proteins has emerged as a promising antiviral strategy. Indeed, many of the approaches that have been investigated in the past few years target host rather than viral components, even when the target is highly selective for one specific virus, as is the case for maraviroc
<sup><xref rid="ref-22" ref-type="bibr">22</xref></sup>. This is in line with a recent trend in the development of antiviral strategies
<sup><xref rid="ref-51" ref-type="bibr">51</xref>,
<xref rid="ref-81" ref-type="bibr">81</xref></sup>. To date, small-molecule interference with viral infection has tended to focus on specific viruses and viral proteins. For a few viruses, HIV, HCV, and herpes, for example, this approach has been very effective. In the case of HIV at least, combinations of compounds targeting key viral enzymes essential for completion of the viral life cycle (e.g. HIV
<italic>Pol-</italic>encoded reverse transcriptase, integrase, and protease) control virus replication in infected patients, substantially improve longevity and life quality, and are now being adopted as pre- and post-exposure prophylactics to prevent virus infection
<sup><xref rid="ref-82" ref-type="bibr">82</xref>,
<xref rid="ref-83" ref-type="bibr">83</xref></sup>. Similarly, nucleoside analogues and protease inhibitors active against HCV have the potential to cure what would otherwise be a lifelong chronic infection often resulting in cirrhosis and liver cancer and only treatable by liver transplantation
<sup><xref rid="ref-84" ref-type="bibr">84</xref></sup>. Though highly successful, these drugs are limited to the treatment of single viruses and are prone to viral resistance mutations rendering them ineffective.</p><p>Conversely, very few drugs are available for use against the majority of other viruses. This is a major concern given the increased emergence (or re-emergence) of new pathogens, often from zoonotic infections (e.g. SARS and MERS), and the enlarged geographical distribution of insect-vectored viruses caused by environmental changes (e.g. Zika and dengue
<sup><xref rid="ref-85" ref-type="bibr">85</xref></sup>). Under these circumstances, targeting host cell pathways as opposed to viral proteins is a viable option for controlling infection. One argument against this approach is the potential toxicity of targeting host cell pathways. Toxicity could be due to the inhibition of critical cellular pathways as well as to off-target effects. However, most of the virus infections that might benefit from this approach establish acute infections for which drug administration could be as short as a few days. Moreover, most drugs currently on the market against a range of diseases target host cell pathways with limited, or acceptable, side effects. Another argument is that virus-targeted antivirals seem to be more potent than cell-targeted ones. This concern is counter-balanced by the potential for broad-spectrum effectiveness of many cell-targeted approaches, which may be critical to rapidly contain emerging viruses. Because of lower potency, these compounds might not stop virus infection completely, but several studies indicate that, in general, any capacity to reduce the viral load gives patients a better chance of establishing effective immune control
<sup><xref rid="ref-86" ref-type="bibr">86</xref>–
<xref rid="ref-89" ref-type="bibr">89</xref></sup>.</p><p>As with the application of anti-retroviral therapies, compounds targeting entry and replication could be used in combination; for example, compounds that inhibit CME could be administered together with compounds that inhibit macropinocytosis and/or endosomal acidification in order to broaden the range of viruses affected and/or increase the effectiveness of the treatment. Although we have focused on virus entry, targeting other cellular pathways, such as ER-associated glycoprotein synthesis, also offers exciting potential for broad-spectrum antiviral development that could broaden potential combination therapies
<sup><xref rid="ref-90" ref-type="bibr">90</xref></sup>. This strategy could also reduce toxicity by allowing the use of lower concentrations of each component in complex formulations.</p><p>While many successful approaches have been described
<italic>in vitro</italic>, an outstanding question is whether they are also effective
<italic>in vivo</italic>. In particular for host-targeted approaches, it will be important to determine safe thresholds that separate an effective decrease in viral load from toxicity. The limited
<italic>in vivo</italic> efficacy of many treatments to date may be due to the pharmacokinetics and bioavailability of the compounds, or possibly to the limited range of conditions that are generally tested
<italic>in vivo</italic> due to the costs, logistics, and restrictions on animal studies. Limited availability of adequate small models that recapitulate disease also contributes to the problem. While more work remains to be done, the approval of drugs like maraviroc and enfuvirtide suggests that targeting viral entry is a promising antiviral strategy warranting further investigation and the integration of different disciplines, from virology to medicinal chemistry.</p></sec></body><back><ack><title>Acknowledgements</title><p>We thank Giorgia Siriaco (University College London) for careful reading of the manuscript and members of the Marsh lab for ongoing discussion on the topics addressed in this article.</p></ack><ref-list><ref id="ref-1"><label>1</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Marsh</surname><given-names>M</given-names></name><name><surname>Helenius</surname><given-names>A</given-names></name></person-group>:
<article-title>Virus entry: open sesame.</article-title><source><italic toggle="yes">Cell.</italic></source><year>2006</year>;<volume>124</volume>(<issue>4</issue>):<fpage>729</fpage>–<lpage>40</lpage>.
<pub-id pub-id-type="doi">10.1016/j.cell.2006.02.007</pub-id><pub-id pub-id-type="pmid">16497584</pub-id></mixed-citation></ref><ref id="ref-2"><label>2</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mercer</surname><given-names>J</given-names></name><name><surname>Schelhaas</surname><given-names>M</given-names></name><name><surname>Helenius</surname><given-names>A</given-names></name></person-group>:
<article-title>Virus entry by endocytosis.</article-title><source><italic toggle="yes">Annu Rev Biochem.</italic></source><year>2010</year>;<volume>79</volume>:<fpage>803</fpage>–<lpage>33</lpage>.
<pub-id pub-id-type="doi">10.1146/annurev-biochem-060208-104626</pub-id><pub-id pub-id-type="pmid">20196649</pub-id></mixed-citation></ref><ref id="ref-3"><label>3</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sánchez-San Martín</surname><given-names>C</given-names></name><name><surname>Liu</surname><given-names>CY</given-names></name><name><surname>Kielian</surname><given-names>M</given-names></name></person-group>:
<article-title>Dealing with low pH: entry and exit of alphaviruses and flaviviruses.</article-title><source><italic toggle="yes">Trends Microbiol.</italic></source><year>2009</year>;<volume>17</volume>(<issue>11</issue>):<fpage>514</fpage>–<lpage>21</lpage>.
<pub-id pub-id-type="doi">10.1016/j.tim.2009.08.002</pub-id><pmc-comment>2783195 </pmc-comment>
<pub-id pub-id-type="pmid">19796949</pub-id></mixed-citation></ref><ref id="ref-4"><label>4</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mercer</surname><given-names>J</given-names></name><name><surname>Helenius</surname><given-names>A</given-names></name></person-group>:
<article-title>Vaccinia virus uses macropinocytosis and apoptotic mimicry to enter host cells.</article-title><source><italic toggle="yes">Science.</italic></source><year>2008</year>;<volume>320</volume>(<issue>5875</issue>):<fpage>531</fpage>–<lpage>5</lpage>.
<pub-id pub-id-type="doi">10.1126/science.1155164</pub-id><pub-id pub-id-type="pmid">18436786</pub-id></mixed-citation><note><p><ext-link ext-link-type="uri" xlink:href="https://f1000.com/prime/1108808">F1000 Recommendation</ext-link></p></note></ref><ref id="ref-5"><label>5</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Moller-Tank</surname><given-names>S</given-names></name><name><surname>Maury</surname><given-names>W</given-names></name></person-group>:
<article-title>Ebola virus entry: a curious and complex series of events.</article-title><source><italic toggle="yes">PLoS Pathog.</italic></source><year>2015</year>;<volume>11</volume>(<issue>4</issue>):<fpage>e100473</fpage>.
<pub-id pub-id-type="doi">10.1371/journal.ppat.1004731</pub-id><pmc-comment>4415789 </pmc-comment>
<pub-id pub-id-type="pmid">25928849</pub-id></mixed-citation></ref><ref id="ref-6"><label>6</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Saeed</surname><given-names>MF</given-names></name><name><surname>Kolokoltsov</surname><given-names>AA</given-names></name><name><surname>Albrecht</surname><given-names>T</given-names></name><etal></etal></person-group>:
<article-title>Cellular entry of ebola virus involves uptake by a macropinocytosis-like mechanism and subsequent trafficking through early and late endosomes.</article-title><source><italic toggle="yes">PLoS Pathog.</italic></source><year>2010</year>;<volume>6</volume>(<issue>9</issue>):<fpage>e1001110</fpage>.
<pub-id pub-id-type="doi">10.1371/journal.ppat.1001110</pub-id><pmc-comment>2940741 </pmc-comment>
<pub-id pub-id-type="pmid">20862315</pub-id></mixed-citation></ref><ref id="ref-7"><label>7</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>WuDunn</surname><given-names>D</given-names></name><name><surname>Spear</surname><given-names>PG</given-names></name></person-group>:
<article-title>Initial interaction of herpes simplex virus with cells is binding to heparan sulfate.</article-title><source><italic toggle="yes">J Virol.</italic></source><year>1989</year>;<volume>63</volume>(<issue>1</issue>):<fpage>52</fpage>–<lpage>8</lpage>.
<pmc-comment>247656 </pmc-comment>
<pub-id pub-id-type="pmid">2535752</pub-id></mixed-citation></ref><ref id="ref-8"><label>8</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Giroglou</surname><given-names>T</given-names></name><name><surname>Florin</surname><given-names>L</given-names></name><name><surname>Schäfer</surname><given-names>F</given-names></name><etal></etal></person-group>:
<article-title>Human papillomavirus infection requires cell surface heparan sulfate.</article-title><source><italic toggle="yes">J Virol.</italic></source><year>2001</year>;<volume>75</volume>(<issue>3</issue>):<fpage>1565</fpage>–<lpage>70</lpage>.
<pub-id pub-id-type="doi">10.1128/JVI.75.3.1565-1570.2001</pub-id><pmc-comment>114064 </pmc-comment>
<pub-id pub-id-type="pmid">11152531</pub-id></mixed-citation></ref><ref id="ref-9"><label>9</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Feldman</surname><given-names>SA</given-names></name><name><surname>Hendry</surname><given-names>RM</given-names></name><name><surname>Beeler</surname><given-names>JA</given-names></name></person-group>:
<article-title>Identification of a linear heparin binding domain for human respiratory syncytial virus attachment glycoprotein G.</article-title><source><italic toggle="yes">J Virol.</italic></source><year>1999</year>;<volume>73</volume>(<issue>8</issue>):<fpage>6610</fpage>–<lpage>7</lpage>.
<pmc-comment>112745 </pmc-comment>
<pub-id pub-id-type="pmid">10400758</pub-id></mixed-citation></ref><ref id="ref-10"><label>10</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Klimyte</surname><given-names>EM</given-names></name><name><surname>Smith</surname><given-names>SE</given-names></name><name><surname>Oreste</surname><given-names>P</given-names></name><etal></etal></person-group>:
<article-title>Inhibition of Human Metapneumovirus Binding to Heparan Sulfate Blocks Infection in Human Lung Cells and Airway Tissues.</article-title><source><italic toggle="yes">J Virol.</italic></source><year>2016</year>;<volume>90</volume>(<issue>20</issue>):<fpage>9237</fpage>–<lpage>50</lpage>.
<pub-id pub-id-type="doi">10.1128/JVI.01362-16</pub-id><pmc-comment>5044844 </pmc-comment>
<pub-id pub-id-type="pmid">27489270</pub-id></mixed-citation></ref><ref id="ref-11"><label>11</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Collett</surname><given-names>MS</given-names></name><name><surname>Hincks</surname><given-names>JR</given-names></name><name><surname>Benschop</surname><given-names>K</given-names></name><etal></etal></person-group>:
<article-title>Antiviral Activity of Pocapavir in a Randomized, Blinded, Placebo-Controlled Human Oral Poliovirus Vaccine Challenge Model.</article-title><source><italic toggle="yes">J Infect Dis.</italic></source><year>2017</year>;<volume>215</volume>(<issue>3</issue>):<fpage>335</fpage>–<lpage>343</lpage>.
<pub-id pub-id-type="doi">10.1093/infdis/jiw542</pub-id><pmc-comment>5393058 </pmc-comment>
<pub-id pub-id-type="pmid">27932608</pub-id></mixed-citation></ref><ref id="ref-12"><label>12</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ghosh</surname><given-names>T</given-names></name><name><surname>Chattopadhyay</surname><given-names>K</given-names></name><name><surname>Marschall</surname><given-names>M</given-names></name><etal></etal></person-group>:
<article-title>Focus on antivirally active sulfated polysaccharides: from structure-activity analysis to clinical evaluation.</article-title><source><italic toggle="yes">Glycobiology.</italic></source><year>2009</year>;<volume>19</volume>(<issue>1</issue>):<fpage>2</fpage>–<lpage>15</lpage>.
<pub-id pub-id-type="doi">10.1093/glycob/cwn092</pub-id><pub-id pub-id-type="pmid">18815291</pub-id></mixed-citation></ref><ref id="ref-13"><label>13</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lee</surname><given-names>E</given-names></name><name><surname>Pavy</surname><given-names>M</given-names></name><name><surname>Young</surname><given-names>N</given-names></name><etal></etal></person-group>:
<article-title>Antiviral effect of the heparan sulfate mimetic, PI-88, against dengue and encephalitic flaviviruses.</article-title><source><italic toggle="yes">Antiviral Res.</italic></source><year>2006</year>;<volume>69</volume>(<issue>1</issue>):<fpage>31</fpage>–<lpage>8</lpage>.
<pub-id pub-id-type="doi">10.1016/j.antiviral.2005.08.006</pub-id><pub-id pub-id-type="pmid">16309754</pub-id></mixed-citation></ref><ref id="ref-14"><label>14</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cagno</surname><given-names>V</given-names></name><name><surname>Andreozzi</surname><given-names>P</given-names></name><name><surname>D’Alicarnasso</surname><given-names>M</given-names></name><etal></etal></person-group>:
<article-title>Broad-spectrum non-toxic antiviral nanoparticles with a virucidal inhibition mechanism.</article-title><source><italic toggle="yes">Nat Mater.</italic></source><year>2018</year>;<volume>17</volume>(<issue>2</issue>):<fpage>195</fpage>–<lpage>203</lpage>.
<pub-id pub-id-type="doi">10.1038/nmat5053</pub-id><pub-id pub-id-type="pmid">29251725</pub-id></mixed-citation><note><p><ext-link ext-link-type="uri" xlink:href="https://f1000.com/prime/732321240">F1000 Recommendation</ext-link></p></note></ref><ref id="ref-15"><label>15</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Botos</surname><given-names>I</given-names></name><name><surname>Wlodawer</surname><given-names>A</given-names></name></person-group>:
<article-title>Cyanovirin-N: a sugar-binding antiviral protein with a new twist.</article-title><source><italic toggle="yes">Cell Mol Life Sci.</italic></source><year>2003</year>;<volume>60</volume>(<issue>2</issue>):<fpage>277</fpage>–<lpage>87</lpage>.
<pub-id pub-id-type="doi">10.1007/s000180300023</pub-id><pub-id pub-id-type="pmid">12678493</pub-id></mixed-citation></ref><ref id="ref-16"><label>16</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Barrientos</surname><given-names>LG</given-names></name><name><surname>O’Keefe</surname><given-names>BR</given-names></name><name><surname>Bray</surname><given-names>M</given-names></name><etal></etal></person-group>:
<article-title>Cyanovirin-N binds to the viral surface glycoprotein, GP
<sub>1,2</sub> and inhibits infectivity of Ebola virus.</article-title><source><italic toggle="yes">Antiviral Res.</italic></source><year>2003</year>;<volume>58</volume>(<issue>1</issue>):<fpage>47</fpage>–<lpage>56</lpage>.
<pub-id pub-id-type="doi">10.1016/S0166-3542(02)00183-3</pub-id><pub-id pub-id-type="pmid">12719006</pub-id></mixed-citation></ref><ref id="ref-17"><label>17</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhou</surname><given-names>Y</given-names></name><name><surname>Simmons</surname><given-names>G</given-names></name></person-group>:
<article-title>Development of novel entry inhibitors targeting emerging viruses.</article-title><source><italic toggle="yes">Expert Rev Anti Infect Ther.</italic></source><year>2012</year>;<volume>10</volume>(<issue>10</issue>):<fpage>1129</fpage>–<lpage>38</lpage>.
<pub-id pub-id-type="doi">10.1586/eri.12.104</pub-id><pmc-comment>3587779 </pmc-comment>
<pub-id pub-id-type="pmid">23199399</pub-id></mixed-citation></ref><ref id="ref-18"><label>18</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Carette</surname><given-names>JE</given-names></name><name><surname>Raaben</surname><given-names>M</given-names></name><name><surname>Wong</surname><given-names>AC</given-names></name><etal></etal></person-group>:
<article-title>Ebola virus entry requires the cholesterol transporter Niemann-Pick C1.</article-title><source><italic toggle="yes">Nature.</italic></source><year>2011</year>;<volume>477</volume>(<issue>7364</issue>):<fpage>340</fpage>–<lpage>3</lpage>.
<pub-id pub-id-type="doi">10.1038/nature10348</pub-id><pmc-comment>3175325 </pmc-comment>
<pub-id pub-id-type="pmid">21866103</pub-id></mixed-citation><note><p><ext-link ext-link-type="uri" xlink:href="https://f1000.com/prime/13200064">F1000 Recommendation</ext-link></p></note></ref><ref id="ref-19"><label>19</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Malakhov</surname><given-names>MP</given-names></name><name><surname>Aschenbrenner</surname><given-names>LM</given-names></name><name><surname>Smee</surname><given-names>DF</given-names></name><etal></etal></person-group>:
<article-title>Sialidase fusion protein as a novel broad-spectrum inhibitor of influenza virus infection.</article-title><source><italic toggle="yes">Antimicrob Agents Chemother.</italic></source><year>2006</year>;<volume>50</volume>(<issue>4</issue>):<fpage>1470</fpage>–<lpage>9</lpage>.
<pub-id pub-id-type="doi">10.1128/AAC.50.4.1470-1479.2006</pub-id><pmc-comment>1426979 </pmc-comment>
<pub-id pub-id-type="pmid">16569867</pub-id></mixed-citation></ref><ref id="ref-20"><label>20</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Moss</surname><given-names>RB</given-names></name><name><surname>Hansen</surname><given-names>C</given-names></name><name><surname>Sanders</surname><given-names>RL</given-names></name><etal></etal></person-group>:
<article-title>A phase II study of DAS181, a novel host directed antiviral for the treatment of influenza infection.</article-title><source><italic toggle="yes">J Infect Dis.</italic></source><year>2012</year>;<volume>206</volume>(<issue>12</issue>):<fpage>1844</fpage>–<lpage>51</lpage>.
<pub-id pub-id-type="doi">10.1093/infdis/jis622</pub-id><pmc-comment>3570175 </pmc-comment>
<pub-id pub-id-type="pmid">23045618</pub-id></mixed-citation><note><p><ext-link ext-link-type="uri" xlink:href="https://f1000.com/prime/717962093">F1000 Recommendation</ext-link></p></note></ref><ref id="ref-21"><label>21</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Li</surname><given-names>F</given-names></name><name><surname>Ma</surname><given-names>C</given-names></name><name><surname>Wang</surname><given-names>J</given-names></name></person-group>:
<article-title>Inhibitors targeting the influenza virus hemagglutinin.</article-title><source><italic toggle="yes">Curr Med Chem.</italic></source><year>2015</year>;<volume>22</volume>(<issue>11</issue>):<fpage>1361</fpage>–<lpage>82</lpage>.
<pub-id pub-id-type="doi">10.2174/0929867322666150227153919</pub-id><pub-id pub-id-type="pmid">25723505</pub-id></mixed-citation></ref><ref id="ref-22"><label>22</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>MacArthur</surname><given-names>RD</given-names></name><name><surname>Novak</surname><given-names>RM</given-names></name></person-group>:
<article-title>Reviews of anti-infective agents: maraviroc: the first of a new class of antiretroviral agents.</article-title><source><italic toggle="yes">Clin Infect Dis.</italic></source><year>2008</year>;<volume>47</volume>(<issue>2</issue>):<fpage>236</fpage>–<lpage>41</lpage>.
<pub-id pub-id-type="doi">10.1086/589289</pub-id><pub-id pub-id-type="pmid">18532888</pub-id></mixed-citation></ref><ref id="ref-23"><label>23</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dorr</surname><given-names>P</given-names></name><name><surname>Westby</surname><given-names>M</given-names></name><name><surname>Dobbs</surname><given-names>S</given-names></name><etal></etal></person-group>:
<article-title>Maraviroc (UK-427,857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum anti-human immunodeficiency virus type 1 activity.</article-title><source><italic toggle="yes">Antimicrob Agents Chemother.</italic></source><year>2005</year>;<volume>49</volume>(<issue>11</issue>):<fpage>4721</fpage>–<lpage>32</lpage>.
<pub-id pub-id-type="doi">10.1128/AAC.49.11.4721-4732.2005</pub-id><pmc-comment>1280117 </pmc-comment>
<pub-id pub-id-type="pmid">16251317</pub-id></mixed-citation></ref><ref id="ref-24"><label>24</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pastore</surname><given-names>C</given-names></name><name><surname>Ramos</surname><given-names>A</given-names></name><name><surname>Mosier</surname><given-names>DE</given-names></name></person-group>:
<article-title>Intrinsic obstacles to human immunodeficiency virus type 1 coreceptor switching.</article-title><source><italic toggle="yes">J Virol.</italic></source><year>2004</year>;<volume>78</volume>(<issue>14</issue>):<fpage>7565</fpage>–<lpage>74</lpage>.
<pub-id pub-id-type="doi">10.1128/JVI.78.14.7565-7574.2004</pub-id><pmc-comment>434079 </pmc-comment>
<pub-id pub-id-type="pmid">15220431</pub-id></mixed-citation></ref><ref id="ref-25"><label>25</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vermeire</surname><given-names>K</given-names></name><name><surname>Bell</surname><given-names>TW</given-names></name><name><surname>van Puyenbroeck</surname><given-names>V</given-names></name><etal></etal></person-group>:
<article-title>Signal peptide-binding drug as a selective inhibitor of co-translational protein translocation.</article-title><source><italic toggle="yes">PLoS Biol.</italic></source><year>2014</year>;<volume>12</volume>(<issue>12</issue>):<fpage>e1002011</fpage>.
<pub-id pub-id-type="doi">10.1371/journal.pbio.1002011</pub-id><pmc-comment>4251836 </pmc-comment>
<pub-id pub-id-type="pmid">25460167</pub-id></mixed-citation></ref><ref id="ref-26"><label>26</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>van Dongen</surname><given-names>MJP</given-names></name><name><surname>Kadam</surname><given-names>RU</given-names></name><name><surname>Juraszek</surname><given-names>J</given-names></name><etal></etal></person-group>:
<article-title>A small-molecule fusion inhibitor of influenza virus is orally active in mice.</article-title><source><italic toggle="yes">Science.</italic></source><year>2019</year>;<volume>363</volume>(<issue>641</issue>): pii: eaar6221.
<pub-id pub-id-type="doi">10.1126/science.aar6221</pub-id><pmc-comment>6457909 </pmc-comment>
<pub-id pub-id-type="pmid">30846569</pub-id></mixed-citation><note><p><ext-link ext-link-type="uri" xlink:href="https://f1000.com/prime/735259693">F1000 Recommendation</ext-link></p></note></ref><ref id="ref-27"><label>27</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jae</surname><given-names>LT</given-names></name><name><surname>Raaben</surname><given-names>M</given-names></name><name><surname>Herbert</surname><given-names>AS</given-names></name><etal></etal></person-group>:
<article-title>Virus entry. Lassa virus entry requires a trigger-induced receptor switch.</article-title><source><italic toggle="yes">Science.</italic></source><year>2014</year>;<volume>344</volume>(<issue>6191</issue>):<fpage>1506</fpage>–<lpage>10</lpage>.
<pub-id pub-id-type="doi">10.1126/science.1252480</pub-id><pmc-comment>4239993 </pmc-comment>
<pub-id pub-id-type="pmid">24970085</pub-id></mixed-citation></ref><ref id="ref-28"><label>28</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wec</surname><given-names>AZ</given-names></name><name><surname>Nyakatura</surname><given-names>EK</given-names></name><name><surname>Herbert</surname><given-names>AS</given-names></name><etal></etal></person-group>:
<article-title>A "Trojan horse" bispecific-antibody strategy for broad protection against ebolaviruses.</article-title><source><italic toggle="yes">Science.</italic></source><year>2016</year>;<volume>354</volume>(<issue>6310</issue>):<fpage>350</fpage>–<lpage>4</lpage>.
<pub-id pub-id-type="doi">10.1126/science.aag3267</pub-id><pmc-comment>5647781 </pmc-comment>
<pub-id pub-id-type="pmid">27608667</pub-id></mixed-citation><note><p><ext-link ext-link-type="uri" xlink:href="https://f1000.com/prime/726724592">F1000 Recommendation</ext-link></p></note></ref><ref id="ref-29"><label>29</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fabozzi</surname><given-names>G</given-names></name><name><surname>Pegu</surname><given-names>A</given-names></name><name><surname>Koup</surname><given-names>RA</given-names></name><etal></etal></person-group>:
<article-title>Bispecific antibodies: Potential immunotherapies for HIV treatment.</article-title><source><italic toggle="yes">Methods.</italic></source><year>2019</year>;<volume>154</volume>:<fpage>118</fpage>–<lpage>24</lpage>.
<pub-id pub-id-type="doi">10.1016/j.ymeth.2018.10.010</pub-id><pmc-comment>6348037 </pmc-comment>
<pub-id pub-id-type="pmid">30352254</pub-id></mixed-citation></ref><ref id="ref-30"><label>30</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Côté</surname><given-names>M</given-names></name><name><surname>Misasi</surname><given-names>J</given-names></name><name><surname>Ren</surname><given-names>T</given-names></name><etal></etal></person-group>:
<article-title>Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection.</article-title><source><italic toggle="yes">Nature.</italic></source><year>2011</year>;<volume>477</volume>(<issue>7364</issue>):<fpage>344</fpage>–<lpage>8</lpage>.
<pub-id pub-id-type="doi">10.1038/nature10380</pub-id><pmc-comment>3230319 </pmc-comment>
<pub-id pub-id-type="pmid">21866101</pub-id></mixed-citation><note><p><ext-link ext-link-type="uri" xlink:href="https://f1000.com/prime/13200956">F1000 Recommendation</ext-link></p></note></ref><ref id="ref-31"><label>31</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Buontempo</surname><given-names>PJ</given-names></name><name><surname>Cox</surname><given-names>S</given-names></name><name><surname>Wright-Minogue</surname><given-names>J</given-names></name><etal></etal></person-group>:
<article-title>SCH 48973: a potent, broad-spectrum, antienterovirus compound.</article-title><source><italic toggle="yes">Antimicrob Agents Chemother.</italic></source><year>1997</year>;<volume>41</volume>(<issue>6</issue>):<fpage>1220</fpage>–<lpage>5</lpage>.
<pub-id pub-id-type="doi">10.1128/AAC.41.6.1220</pub-id><pmc-comment>163890 </pmc-comment>
<pub-id pub-id-type="pmid">9174174</pub-id></mixed-citation></ref><ref id="ref-32"><label>32</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Torres-Torres</surname><given-names>S</given-names></name><name><surname>Myers</surname><given-names>AL</given-names></name><name><surname>Klatte</surname><given-names>JM</given-names></name><etal></etal></person-group>:
<article-title>First use of investigational antiviral drug pocapavir (v-073) for treating neonatal enteroviral sepsis.</article-title><source><italic toggle="yes">Pediatr Infect Dis J.</italic></source><year>2015</year>;<volume>34</volume>(<issue>1</issue>):<fpage>52</fpage>–<lpage>4</lpage>.
<pub-id pub-id-type="doi">10.1097/INF.0000000000000497</pub-id><pub-id pub-id-type="pmid">25229269</pub-id></mixed-citation></ref><ref id="ref-33"><label>33</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Smith</surname><given-names>TJ</given-names></name><name><surname>Kremer</surname><given-names>MJ</given-names></name><name><surname>Luo</surname><given-names>M</given-names></name><etal></etal></person-group>:
<article-title>The site of attachment in human rhinovirus 14 for antiviral agents that inhibit uncoating.</article-title><source><italic toggle="yes">Science.</italic></source><year>1986</year>;<volume>233</volume>(<issue>4770</issue>):<fpage>1286</fpage>–<lpage>93</lpage>.
<pub-id pub-id-type="doi">10.1126/science.3018924</pub-id><pub-id pub-id-type="pmid">3018924</pub-id></mixed-citation></ref><ref id="ref-34"><label>34</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Abdelnabi</surname><given-names>R</given-names></name><name><surname>Geraets</surname><given-names>JA</given-names></name><name><surname>Ma</surname><given-names>Y</given-names></name><etal></etal></person-group>:
<article-title>A novel druggable interprotomer pocket in the capsid of rhino- and enteroviruses.</article-title><source><italic toggle="yes">PLoS Biol.</italic></source><year>2019</year>;<volume>17</volume>(<issue>6</issue>):<fpage>e3000281</fpage>.
<pub-id pub-id-type="doi">10.1371/journal.pbio.3000281</pub-id><pmc-comment>6559632 </pmc-comment>
<pub-id pub-id-type="pmid">31185007</pub-id></mixed-citation><note><p><ext-link ext-link-type="uri" xlink:href="https://f1000.com/prime/735964439">F1000 Recommendation</ext-link></p></note></ref><ref id="ref-35"><label>35</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sun</surname><given-names>L</given-names></name><name><surname>Lee</surname><given-names>H</given-names></name><name><surname>Thibaut</surname><given-names>HJ</given-names></name><etal></etal></person-group>:
<article-title>Viral engagement with host receptors blocked by a novel class of tryptophan dendrimers that targets the 5-fold-axis of the enterovirus-A71 capsid.</article-title><source><italic toggle="yes">PLoS Pathog.</italic></source><year>2019</year>;<volume>15</volume>(<issue>5</issue>):<fpage>e1007760</fpage>.
<pub-id pub-id-type="doi">10.1371/journal.ppat.1007760</pub-id><pmc-comment>6590834 </pmc-comment>
<pub-id pub-id-type="pmid">31071193</pub-id></mixed-citation><note><p><ext-link ext-link-type="uri" xlink:href="https://f1000.com/prime/735735128">F1000 Recommendation</ext-link></p></note></ref><ref id="ref-36"><label>36</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Diehl</surname><given-names>N</given-names></name><name><surname>Schaal</surname><given-names>H</given-names></name></person-group>:
<article-title>Make yourself at home: viral hijacking of the PI3K/Akt signaling pathway.</article-title><source><italic toggle="yes">Viruses.</italic></source><year>2013</year>;<volume>5</volume>(<issue>12</issue>):<fpage>3192</fpage>–<lpage>212</lpage>.
<pub-id pub-id-type="doi">10.3390/v5123192</pub-id><pmc-comment>3967167 </pmc-comment>
<pub-id pub-id-type="pmid">24351799</pub-id></mixed-citation></ref><ref id="ref-37"><label>37</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mazzon</surname><given-names>M</given-names></name><name><surname>Castro</surname><given-names>C</given-names></name><name><surname>Thaa</surname><given-names>B</given-names></name><etal></etal></person-group>:
<article-title>Alphavirus-induced hyperactivation of PI3K/AKT directs pro-viral metabolic changes.</article-title><source><italic toggle="yes">PLoS Pathog.</italic></source><year>2018</year>;<volume>14</volume>(<issue>1</issue>):<fpage>e1006835</fpage>.
<pub-id pub-id-type="doi">10.1371/journal.ppat.1006835</pub-id><pmc-comment>5805360 </pmc-comment>
<pub-id pub-id-type="pmid">29377936</pub-id></mixed-citation></ref><ref id="ref-38"><label>38</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mercer</surname><given-names>J</given-names></name><name><surname>Knébel</surname><given-names>S</given-names></name><name><surname>Schmidt</surname><given-names>FI</given-names></name><etal></etal></person-group>:
<article-title>Vaccinia virus strains use distinct forms of macropinocytosis for host-cell entry.</article-title><source><italic toggle="yes">Proc Natl Acad Sci U S A.</italic></source><year>2010</year>;<volume>107</volume>(<issue>20</issue>):<fpage>9346</fpage>–<lpage>51</lpage>.
<pub-id pub-id-type="doi">10.1073/pnas.1004618107</pub-id><pmc-comment>2889119 </pmc-comment>
<pub-id pub-id-type="pmid">20439710</pub-id></mixed-citation></ref><ref id="ref-39"><label>39</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dutta</surname><given-names>D</given-names></name><name><surname>Williamson</surname><given-names>CD</given-names></name><name><surname>Cole</surname><given-names>NB</given-names></name><etal></etal></person-group>:
<article-title>Pitstop 2 is a potent inhibitor of clathrin-independent endocytosis.</article-title><source><italic toggle="yes">PLoS One.</italic></source><year>2012</year>;<volume>7</volume>(<issue>9</issue>):<fpage>e45799</fpage>.
<pub-id pub-id-type="doi">10.1371/journal.pone.0045799</pub-id><pmc-comment>3448704 </pmc-comment>
<pub-id pub-id-type="pmid">23029248</pub-id></mixed-citation></ref><ref id="ref-40"><label>40</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Macia</surname><given-names>E</given-names></name><name><surname>Ehrlich</surname><given-names>M</given-names></name><name><surname>Massol</surname><given-names>R</given-names></name><etal></etal></person-group>:
<article-title>Dynasore, a cell-permeable inhibitor of dynamin.</article-title><source><italic toggle="yes">Dev Cell.</italic></source><year>2006</year>;<volume>10</volume>(<issue>6</issue>):<fpage>839</fpage>–<lpage>50</lpage>.
<pub-id pub-id-type="doi">10.1016/j.devcel.2006.04.002</pub-id><pub-id pub-id-type="pmid">16740485</pub-id></mixed-citation><note><p><ext-link ext-link-type="uri" xlink:href="https://f1000.com/prime/1032660">F1000 Recommendation</ext-link></p></note></ref><ref id="ref-41"><label>41</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McCluskey</surname><given-names>A</given-names></name><name><surname>Daniel</surname><given-names>JA</given-names></name><name><surname>Hadzic</surname><given-names>G</given-names></name><etal></etal></person-group>:
<article-title>Building a better dynasore: the dyngo compounds potently inhibit dynamin and endocytosis.</article-title><source><italic toggle="yes">Traffic.</italic></source><year>2013</year>;<volume>14</volume>(<issue>12</issue>):<fpage>1272</fpage>–<lpage>89</lpage>.
<pub-id pub-id-type="doi">10.1111/tra.12119</pub-id><pmc-comment>4138991 </pmc-comment>
<pub-id pub-id-type="pmid">24025110</pub-id></mixed-citation></ref><ref id="ref-42"><label>42</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Harper</surname><given-names>CB</given-names></name><name><surname>Martin</surname><given-names>S</given-names></name><name><surname>Nguyen</surname><given-names>TH</given-names></name><etal></etal></person-group>:
<article-title>Dynamin inhibition blocks botulinum neurotoxin type A endocytosis in neurons and delays botulism.</article-title><source><italic toggle="yes">J Biol Chem.</italic></source><year>2011</year>;<volume>286</volume>(<issue>41</issue>):<fpage>35966</fpage>–<lpage>76</lpage>.
<pub-id pub-id-type="doi">10.1074/jbc.M111.283879</pub-id><pmc-comment>3195592 </pmc-comment>
<pub-id pub-id-type="pmid">21832053</pub-id></mixed-citation><note><p><ext-link ext-link-type="uri" xlink:href="https://f1000.com/prime/13294022">F1000 Recommendation</ext-link></p></note></ref><ref id="ref-43"><label>43</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>de Wilde</surname><given-names>AH</given-names></name><name><surname>Jochmans</surname><given-names>D</given-names></name><name><surname>Posthuma</surname><given-names>CC</given-names></name><etal></etal></person-group>:
<article-title>Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture.</article-title><source><italic toggle="yes">Antimicrob Agents Chemother.</italic></source><year>2014</year>;<volume>58</volume>(<issue>8</issue>):<fpage>4875</fpage>–<lpage>84</lpage>.
<pub-id pub-id-type="doi">10.1128/AAC.03011-14</pub-id><pmc-comment>4136071 </pmc-comment>
<pub-id pub-id-type="pmid">24841269</pub-id></mixed-citation></ref><ref id="ref-44"><label>44</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Blaising</surname><given-names>J</given-names></name><name><surname>Lévy</surname><given-names>PL</given-names></name><name><surname>Polyak</surname><given-names>SJ</given-names></name><etal></etal></person-group>:
<article-title>Arbidol inhibits viral entry by interfering with clathrin-dependent trafficking.</article-title><source><italic toggle="yes">Antiviral Res.</italic></source><year>2013</year>;<volume>100</volume>(<issue>1</issue>):<fpage>2159</fpage>.
<pub-id pub-id-type="doi">10.1016/j.antiviral.2013.08.008</pub-id><pub-id pub-id-type="pmid">23981392</pub-id></mixed-citation></ref><ref id="ref-45"><label>45</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mazzon</surname><given-names>M</given-names></name><name><surname>Ortega-Prieto</surname><given-names>AM</given-names></name><name><surname>Imrie</surname><given-names>D</given-names></name><etal></etal></person-group>:
<article-title>Identification of Broad-Spectrum Antiviral Compounds by Targeting Viral Entry.</article-title><source><italic toggle="yes">Viruses.</italic></source><year>2019</year>;<volume>11</volume>(<issue>2</issue>): pii: E176.
<pub-id pub-id-type="doi">10.3390/v11020176</pub-id><pmc-comment>6410080 </pmc-comment>
<pub-id pub-id-type="pmid">30791609</pub-id></mixed-citation></ref><ref id="ref-46"><label>46</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Banbury</surname><given-names>DN</given-names></name><name><surname>Oakley</surname><given-names>JD</given-names></name><name><surname>Sessions</surname><given-names>RB</given-names></name><etal></etal></person-group>:
<article-title>Tyrphostin A23 inhibits internalization of the transferrin receptor by perturbing the interaction between tyrosine motifs and the medium chain subunit of the AP-2 adaptor complex.</article-title><source><italic toggle="yes">J Biol Chem.</italic></source><year>2003</year>;<volume>278</volume>(<issue>14</issue>):<fpage>12022</fpage>–<lpage>8</lpage>.
<pub-id pub-id-type="doi">10.1074/jbc.M211966200</pub-id><pub-id pub-id-type="pmid">12556528</pub-id></mixed-citation></ref><ref id="ref-47"><label>47</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dejonghe</surname><given-names>W</given-names></name><name><surname>Kuenen</surname><given-names>S</given-names></name><name><surname>Mylle</surname><given-names>E</given-names></name><etal></etal></person-group>:
<article-title>Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification.</article-title><source><italic toggle="yes">Nat Commun.</italic></source><year>2016</year>;<volume>7</volume>:<fpage>11710</fpage>.
<pub-id pub-id-type="doi">10.1038/ncomms11710</pub-id><pmc-comment>4899852 </pmc-comment>
<pub-id pub-id-type="pmid">27271794</pub-id></mixed-citation></ref><ref id="ref-48"><label>48</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jurgeit</surname><given-names>A</given-names></name><name><surname>McDowell</surname><given-names>R</given-names></name><name><surname>Moese</surname><given-names>S</given-names></name><etal></etal></person-group>:
<article-title>Niclosamide is a proton carrier and targets acidic endosomes with broad antiviral effects.</article-title><source><italic toggle="yes">PLoS Pathog.</italic></source><year>2012</year>;<volume>8</volume>(<issue>10</issue>):<fpage>e1002976</fpage>.
<pub-id pub-id-type="doi">10.1371/journal.ppat.1002976</pub-id><pmc-comment>3486884 </pmc-comment>
<pub-id pub-id-type="pmid">23133371</pub-id></mixed-citation></ref><ref id="ref-49"><label>49</label><mixed-citation publication-type="book"><person-group person-group-type="author"><name><surname>HAYES</surname><given-names>WJ</given-names></name><name><surname>LAWS</surname><given-names>JR</given-names></name></person-group>:
<article-title>Classes of pesticides</article-title>. In: LAWS H. (ed.)
<source><italic toggle="yes">Handbook of Pesticide Toxicology</italic></source>. New york, NY: Academic press.<year>1991</year><pub-id pub-id-type="doi">10.1016/C2009-0-02709-3</pub-id></mixed-citation></ref><ref id="ref-50"><label>50</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Doms</surname><given-names>RW</given-names></name><name><surname>Moore</surname><given-names>JP</given-names></name></person-group>:
<article-title>HIV-1 membrane fusion: targets of opportunity.</article-title><source><italic toggle="yes">J Cell Biol.</italic></source><year>2000</year>;<volume>151</volume>(<issue>2</issue>):<fpage>F9</fpage>–<lpage>14</lpage>.
<pub-id pub-id-type="doi">10.1083/jcb.151.2.f9</pub-id><pmc-comment>2192632 </pmc-comment>
<pub-id pub-id-type="pmid">11038194</pub-id></mixed-citation></ref><ref id="ref-51"><label>51</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kaufmann</surname><given-names>SHE</given-names></name><name><surname>Dorhoi</surname><given-names>A</given-names></name><name><surname>Hotchkiss</surname><given-names>RS</given-names></name><etal></etal></person-group>:
<article-title>Host-directed therapies for bacterial and viral infections.</article-title><source><italic toggle="yes">Nat Rev Drug Discov.</italic></source><year>2018</year>;<volume>17</volume>(<issue>1</issue>):<fpage>35</fpage>–<lpage>56</lpage>.
<pub-id pub-id-type="doi">10.1038/nrd.2017.162</pub-id><pub-id pub-id-type="pmid">28935918</pub-id></mixed-citation></ref><ref id="ref-52"><label>52</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Savarino</surname><given-names>A</given-names></name><name><surname>Boelaert</surname><given-names>JR</given-names></name><name><surname>Cassone</surname><given-names>A</given-names></name><etal></etal></person-group>:
<article-title>Effects of chloroquine on viral infections: an old drug against today's diseases?</article-title><source><italic toggle="yes">Lancet Infect Dis.</italic></source><year>2003</year>;<volume>3</volume>(<issue>11</issue>):<fpage>722</fpage>–<lpage>7</lpage>.
<pub-id pub-id-type="doi">10.1016/S1473-3099(03)00806-5</pub-id><pub-id pub-id-type="pmid">14592603</pub-id></mixed-citation></ref><ref id="ref-53"><label>53</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Long</surname><given-names>J</given-names></name><name><surname>Wright</surname><given-names>E</given-names></name><name><surname>Molesti</surname><given-names>E</given-names></name><etal></etal></person-group>:
<article-title>Antiviral therapies against Ebola and other emerging viral diseases using existing medicines that block virus entry [version 2; peer review: 2 approved].</article-title><source><italic toggle="yes">F1000Res.</italic></source><year>2015</year>;<volume>4</volume>:<fpage>30</fpage>.
<pub-id pub-id-type="doi">10.12688/f1000research.6085.2</pub-id><pmc-comment>4431382 </pmc-comment>
<pub-id pub-id-type="pmid">26069727</pub-id></mixed-citation></ref><ref id="ref-54"><label>54</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nicholson</surname><given-names>KG</given-names></name><name><surname>Wiselka</surname><given-names>MJ</given-names></name></person-group>:
<article-title>Amantadine for influenza A.</article-title><source><italic toggle="yes">BMJ.</italic></source><year>1991</year>;<volume>302</volume>(<issue>6774</issue>):<fpage>425</fpage>–<lpage>6</lpage>.
<pub-id pub-id-type="doi">10.1136/bmj.302.6774.425</pub-id><pmc-comment>1669349 </pmc-comment>
<pub-id pub-id-type="pmid">2004163</pub-id></mixed-citation></ref><ref id="ref-55"><label>55</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Monto</surname><given-names>AS</given-names></name><name><surname>Arden</surname><given-names>NH</given-names></name></person-group>:
<article-title>Implications of Viral Resistance to Amantadine in Control of Influenza A.</article-title><source><italic toggle="yes">Clin Infect Dis.</italic></source><year>1992</year>;<volume>15</volume>(<issue>2</issue>):<fpage>362</fpage>–<lpage>7</lpage>.
<pub-id pub-id-type="doi">10.1093/clinids/15.2.362</pub-id><pub-id pub-id-type="pmid">1520770</pub-id></mixed-citation></ref><ref id="ref-56"><label>56</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schornberg</surname><given-names>K</given-names></name><name><surname>Matsuyama</surname><given-names>S</given-names></name><name><surname>Kabsch</surname><given-names>K</given-names></name><etal></etal></person-group>:
<article-title>Role of endosomal cathepsins in entry mediated by the Ebola virus glycoprotein.</article-title><source><italic toggle="yes">J Virol.</italic></source><year>2006</year>;<volume>80</volume>(<issue>8</issue>):<fpage>4174</fpage>–<lpage>8</lpage>.
<pub-id pub-id-type="doi">10.1128/JVI.80.8.4174-4178.2006</pub-id><pmc-comment>1440424 </pmc-comment>
<pub-id pub-id-type="pmid">16571833</pub-id></mixed-citation></ref><ref id="ref-57"><label>57</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sakurai</surname><given-names>Y</given-names></name><name><surname>Kolokoltsov</surname><given-names>AA</given-names></name><name><surname>Chen</surname><given-names>CC</given-names></name><etal></etal></person-group>:
<article-title>Ebola virus. Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment.</article-title><source><italic toggle="yes">Science.</italic></source><year>2015</year>;<volume>347</volume>(<issue>6225</issue>):<fpage>995</fpage>–<lpage>8</lpage>.
<pub-id pub-id-type="doi">10.1126/science.1258758</pub-id><pmc-comment>4550587 </pmc-comment>
<pub-id pub-id-type="pmid">25722412</pub-id></mixed-citation><note><p><ext-link ext-link-type="uri" xlink:href="https://f1000.com/prime/725369685">F1000 Recommendation</ext-link></p></note></ref><ref id="ref-58"><label>58</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Xiao</surname><given-names>JH</given-names></name><name><surname>Rijal</surname><given-names>P</given-names></name><name><surname>Schimanski</surname><given-names>L</given-names></name><etal></etal></person-group>:
<article-title>Characterization of Influenza Virus Pseudotyped with Ebolavirus Glycoprotein.</article-title><source><italic toggle="yes">J Virol.</italic></source><year>2018</year>;<volume>92</volume>(<issue>4</issue>): pii: e00941-17.
<pub-id pub-id-type="doi">10.1128/JVI.00941-17</pub-id><pmc-comment>5790926 </pmc-comment>
<pub-id pub-id-type="pmid">29212933</pub-id></mixed-citation></ref><ref id="ref-59"><label>59</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Penny</surname><given-names>CJ</given-names></name><name><surname>Vassileva</surname><given-names>K</given-names></name><name><surname>Jha</surname><given-names>A</given-names></name><etal></etal></person-group>:
<article-title>Mining of Ebola virus entry inhibitors identifies approved drugs as two-pore channel pore blockers.</article-title><source><italic toggle="yes">Biochim Biophys Acta Mol Cell Res.</italic></source><year>2019</year>;<volume>1866</volume>(<issue>7</issue>):<fpage>1151</fpage>–<lpage>1161</lpage>.
<pub-id pub-id-type="doi">10.1016/j.bbamcr.2018.10.022</pub-id><pub-id pub-id-type="pmid">30408544</pub-id></mixed-citation></ref><ref id="ref-60"><label>60</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gunaratne</surname><given-names>GS</given-names></name><name><surname>Yang</surname><given-names>Y</given-names></name><name><surname>Li</surname><given-names>F</given-names></name><etal></etal></person-group>:
<article-title>NAADP-dependent Ca
<sup>2+</sup> signaling regulates Middle East respiratory syndrome-coronavirus pseudovirus translocation through the endolysosomal system.</article-title><source><italic toggle="yes">Cell Calcium.</italic></source><year>2018</year>;<volume>75</volume>:<fpage>30</fpage>–<lpage>41</lpage>.
<pub-id pub-id-type="doi">10.1016/j.ceca.2018.08.003</pub-id><pmc-comment>6251489 </pmc-comment>
<pub-id pub-id-type="pmid">30121440</pub-id></mixed-citation><note><p><ext-link ext-link-type="uri" xlink:href="https://f1000.com/prime/733835801">F1000 Recommendation</ext-link></p></note></ref><ref id="ref-61"><label>61</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nelson</surname><given-names>EA</given-names></name><name><surname>Dyall</surname><given-names>J</given-names></name><name><surname>Hoenen</surname><given-names>T</given-names></name><etal></etal></person-group>:
<article-title>The phosphatidylinositol-3-phosphate 5-kinase inhibitor apilimod blocks filoviral entry and infection.</article-title><source><italic toggle="yes">PLoS Negl Trop Dis.</italic></source><year>2017</year>;<volume>11</volume>(<issue>4</issue>):<fpage>e0005540</fpage>.
<pub-id pub-id-type="doi">10.1371/journal.pntd.0005540</pub-id><pmc-comment>5402990 </pmc-comment>
<pub-id pub-id-type="pmid">28403145</pub-id></mixed-citation><note><p><ext-link ext-link-type="uri" xlink:href="https://f1000.com/prime/727504873">F1000 Recommendation</ext-link></p></note></ref><ref id="ref-62"><label>62</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hover</surname><given-names>S</given-names></name><name><surname>King</surname><given-names>B</given-names></name><name><surname>Hall</surname><given-names>B</given-names></name><etal></etal></person-group>:
<article-title>Modulation of Potassium Channels Inhibits Bunyavirus Infection.</article-title><source><italic toggle="yes">J Biol Chem.</italic></source><year>2016</year>;<volume>291</volume>(<issue>7</issue>):<fpage>3411</fpage>–<lpage>22</lpage>.
<pub-id pub-id-type="doi">10.1074/jbc.M115.692673</pub-id><pmc-comment>4751384 </pmc-comment>
<pub-id pub-id-type="pmid">26677217</pub-id></mixed-citation></ref><ref id="ref-63"><label>63</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fung</surname><given-names>HB</given-names></name><name><surname>Guo</surname><given-names>Y</given-names></name></person-group>:
<article-title>Enfuvirtide: a fusion inhibitor for the treatment of HIV infection.</article-title><source><italic toggle="yes">Clin Ther.</italic></source><year>2004</year>;<volume>26</volume>(<issue>3</issue>):<fpage>352</fpage>–<lpage>78</lpage>.
<pub-id pub-id-type="doi">10.1016/S0149-2918(04)90032-X</pub-id><pub-id pub-id-type="pmid">15110129</pub-id></mixed-citation></ref><ref id="ref-64"><label>64</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Battles</surname><given-names>MB</given-names></name><name><surname>Langedijk</surname><given-names>JP</given-names></name><name><surname>Furmanova-Hollenstein</surname><given-names>P</given-names></name><etal></etal></person-group>:
<article-title>Molecular mechanism of respiratory syncytial virus fusion inhibitors.</article-title><source><italic toggle="yes">Nat Chem Biol.</italic></source><year>2016</year>;<volume>12</volume>(<issue>2</issue>):<fpage>87</fpage>–<lpage>93</lpage>.
<pub-id pub-id-type="doi">10.1038/nchembio.1982</pub-id><pmc-comment>4731865 </pmc-comment>
<pub-id pub-id-type="pmid">26641933</pub-id></mixed-citation><note><p><ext-link ext-link-type="uri" xlink:href="https://f1000.com/prime/725996447">F1000 Recommendation</ext-link></p></note></ref><ref id="ref-65"><label>65</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Roymans</surname><given-names>D</given-names></name><name><surname>Alnajjar</surname><given-names>SS</given-names></name><name><surname>Battles</surname><given-names>MB</given-names></name><etal></etal></person-group>:
<article-title>Therapeutic efficacy of a respiratory syncytial virus fusion inhibitor.</article-title><source><italic toggle="yes">Nat Commun.</italic></source><year>2017</year>;<volume>8</volume>(<issue>1</issue>):<fpage>167</fpage>.
<pub-id pub-id-type="doi">10.1038/s41467-017-00170-x</pub-id><pmc-comment>5537225 </pmc-comment>
<pub-id pub-id-type="pmid">28761099</pub-id></mixed-citation><note><p><ext-link ext-link-type="uri" xlink:href="https://f1000.com/prime/727865799">F1000 Recommendation</ext-link></p></note></ref><ref id="ref-66"><label>66</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mathieu</surname><given-names>C</given-names></name><name><surname>Huey</surname><given-names>D</given-names></name><name><surname>Jurgens</surname><given-names>E</given-names></name><etal></etal></person-group>:
<article-title>Prevention of measles virus infection by intranasal delivery of fusion inhibitor peptides.</article-title><source><italic toggle="yes">J Virol.</italic></source><year>2015</year>;<volume>89</volume>(<issue>2</issue>):<fpage>1143</fpage>–<lpage>55</lpage>.
<pub-id pub-id-type="doi">10.1128/JVI.02417-14</pub-id><pmc-comment>4300632 </pmc-comment>
<pub-id pub-id-type="pmid">25378493</pub-id></mixed-citation></ref><ref id="ref-67"><label>67</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Porotto</surname><given-names>M</given-names></name><name><surname>Rockx</surname><given-names>B</given-names></name><name><surname>Yokoyama</surname><given-names>CC</given-names></name><etal></etal></person-group>:
<article-title>Inhibition of Nipah Virus Infection In Vivo: Targeting an Early Stage of Paramyxovirus Fusion Activation during Viral Entry.</article-title><source><italic toggle="yes">PLoS Pathog.</italic></source><year>2010</year>;<volume>6</volume>(<issue>10</issue>):<fpage>e1001168</fpage>.
<pub-id pub-id-type="doi">10.1371/journal.ppat.1001168</pub-id><pmc-comment>2965769 </pmc-comment>
<pub-id pub-id-type="pmid">21060819</pub-id></mixed-citation><note><p><ext-link ext-link-type="uri" xlink:href="https://f1000.com/prime/5972956">F1000 Recommendation</ext-link></p></note></ref><ref id="ref-68"><label>68</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chao</surname><given-names>LH</given-names></name><name><surname>Jang</surname><given-names>J</given-names></name><name><surname>Johnson</surname><given-names>A</given-names></name><etal></etal></person-group>:
<article-title>How small-molecule inhibitors of dengue-virus infection interfere with viral membrane fusion.</article-title><source><italic toggle="yes">eLife.</italic></source><year>2018</year>;<volume>7</volume>: pii: e36461.
<pub-id pub-id-type="doi">10.7554/eLife.36461</pub-id><pmc-comment>6056230 </pmc-comment>
<pub-id pub-id-type="pmid">29999491</pub-id></mixed-citation><note><p><ext-link ext-link-type="uri" xlink:href="https://f1000.com/prime/733623487">F1000 Recommendation</ext-link></p></note></ref><ref id="ref-69"><label>69</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schmidt</surname><given-names>AG</given-names></name><name><surname>Yang</surname><given-names>PL</given-names></name><name><surname>Harrison</surname><given-names>SC</given-names></name></person-group>:
<article-title>Peptide Inhibitors of Flavivirus Entry Derived from the E Protein Stem.</article-title><source><italic toggle="yes">J Virol.</italic></source><year>2010</year>;<volume>84</volume>(<issue>24</issue>):<fpage>12549</fpage>–<lpage>54</lpage>.
<pub-id pub-id-type="doi">10.1128/JVI.01440-10</pub-id><pmc-comment>3004314 </pmc-comment>
<pub-id pub-id-type="pmid">20881042</pub-id></mixed-citation></ref><ref id="ref-70"><label>70</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stiasny</surname><given-names>K</given-names></name><name><surname>Heinz</surname><given-names>FX</given-names></name></person-group>:
<article-title>Effect of Membrane Curvature-Modifying Lipids on Membrane Fusion by Tick-Borne Encephalitis Virus.</article-title><source><italic toggle="yes">J Virol.</italic></source><year>2004</year>;<volume>78</volume>(<issue>16</issue>):<fpage>8536</fpage>–<lpage>42</lpage>.
<pub-id pub-id-type="doi">10.1128/JVI.78.16.8536-8542.2004</pub-id><pmc-comment>479076 </pmc-comment>
<pub-id pub-id-type="pmid">15280462</pub-id></mixed-citation></ref><ref id="ref-71"><label>71</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>McMahon</surname><given-names>HT</given-names></name><name><surname>Boucrot</surname><given-names>E</given-names></name></person-group>:
<article-title>Membrane curvature at a glance.</article-title><source><italic toggle="yes">J Cell Sci.</italic></source><year>2015</year>;<volume>128</volume>(<issue>6</issue>):<fpage>1065</fpage>–<lpage>70</lpage>.
<pub-id pub-id-type="doi">10.1242/jcs.114454</pub-id><pmc-comment>4359918 </pmc-comment>
<pub-id pub-id-type="pmid">25774051</pub-id></mixed-citation></ref><ref id="ref-72"><label>72</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Weston</surname><given-names>S</given-names></name><name><surname>Czieso</surname><given-names>S</given-names></name><name><surname>White</surname><given-names>IJ</given-names></name><etal></etal></person-group>:
<article-title>Alphavirus Restriction by IFITM Proteins.</article-title><source><italic toggle="yes">Traffic.</italic></source><year>2016</year>;<volume>17</volume>(<issue>9</issue>):<fpage>997</fpage>–<lpage>1013</lpage>.
<pub-id pub-id-type="doi">10.1111/tra.12416</pub-id><pmc-comment>5025721 </pmc-comment>
<pub-id pub-id-type="pmid">27219333</pub-id></mixed-citation></ref><ref id="ref-73"><label>73</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Smith</surname><given-names>S</given-names></name><name><surname>Weston</surname><given-names>S</given-names></name><name><surname>Kellam</surname><given-names>P</given-names></name><etal></etal></person-group>:
<article-title>IFITM proteins-cellular inhibitors of viral entry.</article-title><source><italic toggle="yes">Curr Opin Virol.</italic></source><year>2014</year>;<volume>4</volume>:<fpage>71</fpage>–<lpage>7</lpage>.
<pub-id pub-id-type="doi">10.1016/j.coviro.2013.11.004</pub-id><pub-id pub-id-type="pmid">24480526</pub-id></mixed-citation></ref><ref id="ref-74"><label>74</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Buchrieser</surname><given-names>J</given-names></name><name><surname>Degrelle</surname><given-names>SA</given-names></name><name><surname>Couderc</surname><given-names>T</given-names></name><etal></etal></person-group>:
<article-title>IFITM proteins inhibit placental syncytiotrophoblast formation and promote fetal demise.</article-title><source><italic toggle="yes">Science.</italic></source><year>2019</year>;<volume>365</volume>(<issue>6449</issue>):<fpage>176</fpage>–<lpage>180</lpage>.
<pub-id pub-id-type="pmid">31296770</pub-id></mixed-citation><note><p><ext-link ext-link-type="uri" xlink:href="https://f1000.com/prime/736185701">F1000 Recommendation</ext-link></p></note></ref><ref id="ref-75"><label>75</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Johansen</surname><given-names>LM</given-names></name><name><surname>Brannan</surname><given-names>JM</given-names></name><name><surname>Delos</surname><given-names>SE</given-names></name><etal></etal></person-group>:
<article-title>FDA-Approved Selective Estrogen Receptor Modulators Inhibit Ebola Virus Infection.</article-title><source><italic toggle="yes">Sci Transl Med.</italic></source><year>2013</year>;<volume>5</volume>(<issue>190</issue>):<fpage>190ra79</fpage>.
<pub-id pub-id-type="doi">10.1126/scitranslmed.3005471</pub-id><pmc-comment>3955358 </pmc-comment>
<pub-id pub-id-type="pmid">23785035</pub-id></mixed-citation><note><p><ext-link ext-link-type="uri" xlink:href="https://f1000.com/prime/718030692">F1000 Recommendation</ext-link></p></note></ref><ref id="ref-76"><label>76</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Salata</surname><given-names>C</given-names></name><name><surname>Baritussio</surname><given-names>A</given-names></name><name><surname>Munegato</surname><given-names>D</given-names></name><etal></etal></person-group>:
<article-title>Amiodarone and metabolite MDEA inhibit Ebola virus infection by interfering with the viral entry process.</article-title><source><italic toggle="yes">Pathog Dis.</italic></source><year>2015</year>;<volume>73</volume>(<issue>5</issue>): pii: ftv032.
<pub-id pub-id-type="doi">10.1093/femspd/ftv032</pub-id><pub-id pub-id-type="pmid">25933611</pub-id></mixed-citation></ref><ref id="ref-77"><label>77</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Turone</surname><given-names>F</given-names></name></person-group>:
<article-title>Doctors trial amiodarone for Ebola in Sierra Leone.</article-title><source><italic toggle="yes">BMJ.</italic></source><year>2014</year>;<volume>349</volume>:<fpage>g7198</fpage>.
<pub-id pub-id-type="doi">10.1136/bmj.g7198</pub-id><pub-id pub-id-type="pmid">25429872</pub-id></mixed-citation></ref><ref id="ref-78"><label>78</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Han</surname><given-names>Y</given-names></name><name><surname>Mesplède</surname><given-names>T</given-names></name><name><surname>Xu</surname><given-names>H</given-names></name><etal></etal></person-group>:
<article-title>The antimalarial drug amodiaquine possesses anti-ZIKA virus activities</article-title><source><italic toggle="yes">J Med Virol.</italic></source><year>2018</year>;<volume>90</volume>(<issue>5</issue>):<fpage>796</fpage>–<lpage>802</lpage>.
<pub-id pub-id-type="doi">10.1002/jmv.25031</pub-id><pub-id pub-id-type="pmid">29315671</pub-id></mixed-citation></ref><ref id="ref-79"><label>79</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vigant</surname><given-names>F</given-names></name><name><surname>Lee</surname><given-names>J</given-names></name><name><surname>Hollmann</surname><given-names>A</given-names></name><etal></etal></person-group>:
<article-title>A Mechanistic Paradigm for Broad-Spectrum Antivirals that Target Virus-Cell Fusion.</article-title><source><italic toggle="yes">PLoS Pathog.</italic></source><year>2013</year>;<volume>9</volume>(<issue>4</issue>):<fpage>e1003297</fpage>.
<pub-id pub-id-type="doi">10.1371/journal.ppat.1003297</pub-id><pmc-comment>3630091 </pmc-comment>
<pub-id pub-id-type="pmid">23637597</pub-id></mixed-citation><note><p><ext-link ext-link-type="uri" xlink:href="https://f1000.com/prime/718172855">F1000 Recommendation</ext-link></p></note></ref><ref id="ref-80"><label>80</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wolf</surname><given-names>MC</given-names></name><name><surname>Freiberg</surname><given-names>AN</given-names></name><name><surname>Zhang</surname><given-names>T</given-names></name><etal></etal></person-group>:
<article-title>A broad-spectrum antiviral targeting entry of enveloped viruses.</article-title><source><italic toggle="yes">Proc Natl Acad Sci U S A.</italic></source><year>2010</year>;<volume>107</volume>(<issue>7</issue>):<fpage>3157</fpage>–<lpage>62</lpage>.
<pub-id pub-id-type="doi">10.1073/pnas.0909587107</pub-id><pmc-comment>2840368 </pmc-comment>
<pub-id pub-id-type="pmid">20133606</pub-id></mixed-citation><note><p><ext-link ext-link-type="uri" xlink:href="https://f1000.com/prime/2513957">F1000 Recommendation</ext-link></p></note></ref><ref id="ref-81"><label>81</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhu</surname><given-names>JD</given-names></name><name><surname>Meng</surname><given-names>W</given-names></name><name><surname>Wang</surname><given-names>XJ</given-names></name><etal></etal></person-group>:
<article-title>Broad-spectrum antiviral agents.</article-title><source><italic toggle="yes">Front Microbiol.</italic></source><year>2015</year>;<volume>6</volume>:<fpage>517</fpage>.
<pub-id pub-id-type="doi">10.3389/fmicb.2015.00517</pub-id><pmc-comment>4440912 </pmc-comment>
<pub-id pub-id-type="pmid">26052325</pub-id></mixed-citation></ref><ref id="ref-82"><label>82</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lu</surname><given-names>DY</given-names></name><name><surname>Wu</surname><given-names>HY</given-names></name><name><surname>Yarla</surname><given-names>NS</given-names></name><etal></etal></person-group>:
<article-title>HAART in HIV/AIDS Treatments: Future Trends.</article-title><source><italic toggle="yes">Infect Disord Drug Targets.</italic></source><year>2018</year>;<volume>18</volume>(<issue>1</issue>):<fpage>15</fpage>–<lpage>22</lpage>.
<pub-id pub-id-type="doi">10.2174/1871526517666170505122800</pub-id><pub-id pub-id-type="pmid">28474549</pub-id></mixed-citation><note><p><ext-link ext-link-type="uri" xlink:href="https://f1000.com/prime/736511922">F1000 Recommendation</ext-link></p></note></ref><ref id="ref-83"><label>83</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ford</surname><given-names>N</given-names></name><name><surname>Shubber</surname><given-names>Z</given-names></name><name><surname>Calmy</surname><given-names>A</given-names></name><etal></etal></person-group>:
<article-title>Choice of Antiretroviral Drugs for Postexposure Prophylaxis for Adults and Adolescents: A Systematic Review.</article-title><source><italic toggle="yes">Clin Infect Dis.</italic></source><year>2015</year>;<volume>60 Suppl 3</volume>:<fpage>S170</fpage>–<lpage>S176</lpage>.
<pub-id pub-id-type="doi">10.1093/cid/civ092</pub-id><pub-id pub-id-type="pmid">25972499</pub-id></mixed-citation></ref><ref id="ref-84"><label>84</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kirby</surname><given-names>BJ</given-names></name><name><surname>Symonds</surname><given-names>WT</given-names></name><name><surname>Kearney</surname><given-names>BP</given-names></name><etal></etal></person-group>:
<article-title>Pharmacokinetic, Pharmacodynamic, and Drug-Interaction Profile of the Hepatitis C Virus NS5B Polymerase Inhibitor Sofosbuvir.</article-title><source><italic toggle="yes">Clin Pharmacokinet.</italic></source><year>2015</year>;<volume>54</volume>(<issue>7</issue>):<fpage>677</fpage>–<lpage>90</lpage>.
<pub-id pub-id-type="doi">10.1007/s40262-015-0261-7</pub-id><pub-id pub-id-type="pmid">25822283</pub-id></mixed-citation></ref><ref id="ref-85"><label>85</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bekerman</surname><given-names>E</given-names></name><name><surname>Einav</surname><given-names>S</given-names></name></person-group>:
<article-title>Infectious disease. Combating emerging viral threats.</article-title><source><italic toggle="yes">Science.</italic></source><year>2015</year>;<volume>348</volume>(<issue>6232</issue>):<fpage>282</fpage>–<lpage>3</lpage>.
<pub-id pub-id-type="doi">10.1126/science.aaa3778</pub-id><pmc-comment>4419706 </pmc-comment>
<pub-id pub-id-type="pmid">25883340</pub-id></mixed-citation></ref><ref id="ref-86"><label>86</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cross</surname><given-names>RW</given-names></name><name><surname>Mire</surname><given-names>CE</given-names></name><name><surname>Feldmann</surname><given-names>H</given-names></name><etal></etal></person-group>:
<article-title>Post-exposure treatments for Ebola and Marburg virus infections.</article-title><source><italic toggle="yes">Nat Rev Drug Discov.</italic></source><year>2018</year>;<volume>17</volume>:<fpage>413</fpage>–<lpage>34</lpage>.
<pub-id pub-id-type="doi">10.1038/nrd.2018.73</pub-id><pub-id pub-id-type="pmid">29375139</pub-id></mixed-citation></ref><ref id="ref-87"><label>87</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>de La Vega</surname><given-names>MA</given-names></name><name><surname>Caleo</surname><given-names>G</given-names></name><name><surname>Audet</surname><given-names>J</given-names></name><etal></etal></person-group>:
<article-title>Ebola viral load at diagnosis associates with patient outcome and outbreak evolution.</article-title><source><italic toggle="yes">J Clin Invest.</italic></source><year>2015</year>;<volume>125</volume>(<issue>12</issue>):<fpage>4421</fpage>–<lpage>8</lpage>.
<pub-id pub-id-type="doi">10.1172/JCI83162</pub-id><pmc-comment>4665775 </pmc-comment>
<pub-id pub-id-type="pmid">26551677</pub-id></mixed-citation></ref><ref id="ref-88"><label>88</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Thi</surname><given-names>EP</given-names></name><name><surname>Lee</surname><given-names>ACH</given-names></name><name><surname>Geisbert</surname><given-names>JB</given-names></name><etal></etal></person-group>:
<article-title>Rescue of non-human primates from advanced Sudan ebolavirus infection with lipid encapsulated siRNA.</article-title><source><italic toggle="yes">Nat Microbiol.</italic></source><year>2016</year>;<volume>1</volume>(<issue>10</issue>):<fpage>16142</fpage>.
<pub-id pub-id-type="doi">10.1038/nmicrobiol.2016.142</pub-id><pmc-comment>5154560 </pmc-comment>
<pub-id pub-id-type="pmid">27670117</pub-id></mixed-citation><note><p><ext-link ext-link-type="uri" xlink:href="https://f1000.com/prime/726824076">F1000 Recommendation</ext-link></p></note></ref><ref id="ref-89"><label>89</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vaughn</surname><given-names>DW</given-names></name><name><surname>Green</surname><given-names>S</given-names></name><name><surname>Kalayanarooj</surname><given-names>S</given-names></name><etal></etal></person-group>:
<article-title>Dengue Viremia Titer, Antibody Response Pattern, and Virus Serotype Correlate with Disease Severity.</article-title><source><italic toggle="yes">J Infect Dis.</italic></source><year>2000</year>;<volume>181</volume>(<issue>1</issue>):<fpage>2</fpage>–<lpage>9</lpage>.
<pub-id pub-id-type="doi">10.1086/315215</pub-id><pub-id pub-id-type="pmid">10608744</pub-id></mixed-citation></ref><ref id="ref-90"><label>90</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dwek</surname><given-names>RA</given-names></name><name><surname>Butters</surname><given-names>TD</given-names></name><name><surname>Platt</surname><given-names>FM</given-names></name><etal></etal></person-group>:
<article-title>Targeting glycosylation as a therapeutic approach.</article-title><source><italic toggle="yes">Nat Rev Drug Discov.</italic></source><year>2002</year>;<volume>1</volume>(<issue>1</issue>):<fpage>65</fpage>–<lpage>75</lpage>.
<pub-id pub-id-type="doi">10.1038/nrd708</pub-id><pub-id pub-id-type="pmid">12119611</pub-id></mixed-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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