Design, Synthesis, and Anti-RNA Virus Activity of 6'-Fluorinated-Aristeromycin Analogues.
Identifieur interne : 000498 ( PubMed/Curation ); précédent : 000497; suivant : 000499Design, Synthesis, and Anti-RNA Virus Activity of 6'-Fluorinated-Aristeromycin Analogues.
Auteurs : Ji-Seong Yoon [Corée du Sud] ; Gyudong Kim [Corée du Sud] ; Dnyandev B. Jarhad [Corée du Sud] ; Hong-Rae Kim [Corée du Sud] ; Young-Sup Shin [Corée du Sud] ; Shuhao Qu [Corée du Sud] ; Pramod K. Sahu [Corée du Sud] ; Hea Ok Kim [Corée du Sud] ; Hyuk Woo Lee [Corée du Sud] ; Su Bin Wang [Corée du Sud] ; Yun Jeong Kong [Corée du Sud] ; Tong-Shin Chang [Corée du Sud] ; Natacha S. Ogando [Pays-Bas] ; Kristina Kovacikova [Pays-Bas] ; Eric J. Snijder [Pays-Bas] ; Clara C. Posthuma [Pays-Bas] ; Martijn J. Van Hemert [Pays-Bas] ; Lak Shin Jeong [Corée du Sud]Source :
- Journal of medicinal chemistry [ 1520-4804 ] ; 2019.
Abstract
The 6'-fluorinated aristeromycins were designed as dual-target antiviral compounds aimed at inhibiting both the viral RNA-dependent RNA polymerase (RdRp) and the host cell S-adenosyl-l-homocysteine (SAH) hydrolase, which would indirectly target capping of viral RNA. The introduction of a fluorine at the 6'-position enhanced the inhibition of SAH hydrolase and the activity against RNA viruses. The adenosine and N6-methyladenosine analogues 2a-e showed potent inhibition against SAH hydrolase, while only the adenosine derivatives 2a-c exhibited potent antiviral activity against all tested RNA viruses such as Middle East respiratory syndrome-coronavirus (MERS-CoV), severe acute respiratory syndrome-coronavirus, chikungunya virus, and/or Zika virus. 6',6'-Difluoroaristeromycin (2c) showed the strongest antiviral effect for MERS-CoV, with a ∼2.5 log reduction in infectious progeny titer in viral load reduction assay. The phosphoramidate prodrug 3a also demonstrated potent broad-spectrum antiviral activity, possibly by inhibiting the viral RdRp. This study shows that 6'-fluorinated aristeromycins can serve as starting points for the development of broad-spectrum antiviral agents that target RNA viruses.
DOI: 10.1021/acs.jmedchem.9b00781
PubMed: 31244113
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Jarhad</name><affiliation wicri:level="1"><nlm:affiliation>Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 151-742 , Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 151-742 </wicri:regionArea></affiliation></author><author><name sortKey="Kim, Hong Rae" sort="Kim, Hong Rae" uniqKey="Kim H" first="Hong-Rae" last="Kim">Hong-Rae Kim</name><affiliation wicri:level="1"><nlm:affiliation>Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 151-742 , Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 151-742 </wicri:regionArea></affiliation></author><author><name sortKey="Shin, Young Sup" sort="Shin, Young Sup" uniqKey="Shin Y" first="Young-Sup" last="Shin">Young-Sup Shin</name><affiliation wicri:level="1"><nlm:affiliation>Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 151-742 , Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 151-742 </wicri:regionArea></affiliation></author><author><name sortKey="Qu, Shuhao" sort="Qu, Shuhao" uniqKey="Qu S" first="Shuhao" last="Qu">Shuhao Qu</name><affiliation wicri:level="1"><nlm:affiliation>Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 151-742 , Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 151-742 </wicri:regionArea></affiliation></author><author><name sortKey="Sahu, Pramod K" sort="Sahu, Pramod K" uniqKey="Sahu P" first="Pramod K" last="Sahu">Pramod K. Sahu</name><affiliation wicri:level="1"><nlm:affiliation>Future Medicine Co., Ltd. , Seoul 06665 , Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Future Medicine Co., Ltd. , Seoul 06665 </wicri:regionArea></affiliation></author><author><name sortKey="Kim, Hea Ok" sort="Kim, Hea Ok" uniqKey="Kim H" first="Hea Ok" last="Kim">Hea Ok Kim</name><affiliation wicri:level="1"><nlm:affiliation>Future Medicine Co., Ltd. , Seoul 06665 , Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Future Medicine Co., Ltd. , Seoul 06665 </wicri:regionArea></affiliation></author><author><name sortKey="Lee, Hyuk Woo" sort="Lee, Hyuk Woo" uniqKey="Lee H" first="Hyuk Woo" last="Lee">Hyuk Woo Lee</name><affiliation wicri:level="1"><nlm:affiliation>Future Medicine Co., Ltd. , Seoul 06665 , Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Future Medicine Co., Ltd. , Seoul 06665 </wicri:regionArea></affiliation></author><author><name sortKey="Wang, Su Bin" sort="Wang, Su Bin" uniqKey="Wang S" first="Su Bin" last="Wang">Su Bin Wang</name><affiliation wicri:level="1"><nlm:affiliation>College of Pharmacy , Ewha Womans University , Seoul 120-750 , Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>College of Pharmacy , Ewha Womans University , Seoul 120-750 </wicri:regionArea></affiliation></author><author><name sortKey="Kong, Yun Jeong" sort="Kong, Yun Jeong" uniqKey="Kong Y" first="Yun Jeong" last="Kong">Yun Jeong Kong</name><affiliation wicri:level="1"><nlm:affiliation>College of Pharmacy , Ewha Womans University , Seoul 120-750 , Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>College of Pharmacy , Ewha Womans University , Seoul 120-750 </wicri:regionArea></affiliation></author><author><name sortKey="Chang, Tong Shin" sort="Chang, Tong Shin" uniqKey="Chang T" first="Tong-Shin" last="Chang">Tong-Shin Chang</name><affiliation wicri:level="1"><nlm:affiliation>Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 151-742 , Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 151-742 </wicri:regionArea></affiliation></author><author><name sortKey="Ogando, Natacha S" sort="Ogando, Natacha S" uniqKey="Ogando N" first="Natacha S" last="Ogando">Natacha S. Ogando</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Microbiology , Leiden University Medical Center , Albinusdreef 2 , 2333ZA Leiden , The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Microbiology , Leiden University Medical Center , Albinusdreef 2 , 2333ZA Leiden </wicri:regionArea></affiliation></author><author><name sortKey="Kovacikova, Kristina" sort="Kovacikova, Kristina" uniqKey="Kovacikova K" first="Kristina" last="Kovacikova">Kristina Kovacikova</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Microbiology , Leiden University Medical Center , Albinusdreef 2 , 2333ZA Leiden , The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Microbiology , Leiden University Medical Center , Albinusdreef 2 , 2333ZA Leiden </wicri:regionArea></affiliation></author><author><name sortKey="Snijder, Eric J" sort="Snijder, Eric J" uniqKey="Snijder E" first="Eric J" last="Snijder">Eric J. Snijder</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Microbiology , Leiden University Medical Center , Albinusdreef 2 , 2333ZA Leiden , The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Microbiology , Leiden University Medical Center , Albinusdreef 2 , 2333ZA Leiden </wicri:regionArea></affiliation></author><author><name sortKey="Posthuma, Clara C" sort="Posthuma, Clara C" uniqKey="Posthuma C" first="Clara C" last="Posthuma">Clara C. Posthuma</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Microbiology , Leiden University Medical Center , Albinusdreef 2 , 2333ZA Leiden , The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Microbiology , Leiden University Medical Center , Albinusdreef 2 , 2333ZA Leiden </wicri:regionArea></affiliation></author><author><name sortKey="Van Hemert, Martijn J" sort="Van Hemert, Martijn J" uniqKey="Van Hemert M" first="Martijn J" last="Van Hemert">Martijn J. Van Hemert</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Microbiology , Leiden University Medical Center , Albinusdreef 2 , 2333ZA Leiden , The Netherlands.</nlm:affiliation><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Microbiology , Leiden University Medical Center , Albinusdreef 2 , 2333ZA Leiden </wicri:regionArea></affiliation></author><author><name sortKey="Jeong, Lak Shin" sort="Jeong, Lak Shin" uniqKey="Jeong L" first="Lak Shin" last="Jeong">Lak Shin Jeong</name><affiliation wicri:level="1"><nlm:affiliation>Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 151-742 , Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 151-742 </wicri:regionArea></affiliation></author></analytic><series><title level="j">Journal of medicinal chemistry</title><idno type="eISSN">1520-4804</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The 6'-fluorinated aristeromycins were designed as dual-target antiviral compounds aimed at inhibiting both the viral RNA-dependent RNA polymerase (RdRp) and the host cell <i>S</i>-adenosyl-l-homocysteine (SAH) hydrolase, which would indirectly target capping of viral RNA. The introduction of a fluorine at the 6'-position enhanced the inhibition of SAH hydrolase and the activity against RNA viruses. The adenosine and <i>N</i><sup>6</sup>-methyladenosine analogues <b>2a-e</b> showed potent inhibition against SAH hydrolase, while only the adenosine derivatives <b>2a-c</b> exhibited potent antiviral activity against all tested RNA viruses such as Middle East respiratory syndrome-coronavirus (MERS-CoV), severe acute respiratory syndrome-coronavirus, chikungunya virus, and/or Zika virus. 6',6'-Difluoroaristeromycin (<b>2c</b>) showed the strongest antiviral effect for MERS-CoV, with a ∼2.5 log reduction in infectious progeny titer in viral load reduction assay. The phosphoramidate prodrug <b>3a</b> also demonstrated potent broad-spectrum antiviral activity, possibly by inhibiting the viral RdRp. This study shows that 6'-fluorinated aristeromycins can serve as starting points for the development of broad-spectrum antiviral agents that target RNA viruses.</div></front></TEI><pubmed><MedlineCitation Status="In-Data-Review" Owner="NLM"><PMID Version="1">31244113</PMID><DateRevised><Year>2020</Year><Month>03</Month><Day>19</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1520-4804</ISSN><JournalIssue CitedMedium="Internet"><Volume>62</Volume><Issue>13</Issue><PubDate><Year>2019</Year><Month>Jul</Month><Day>11</Day></PubDate></JournalIssue><Title>Journal of medicinal chemistry</Title><ISOAbbreviation>J. Med. Chem.</ISOAbbreviation></Journal><ArticleTitle>Design, Synthesis, and Anti-RNA Virus Activity of 6'-Fluorinated-Aristeromycin Analogues.</ArticleTitle><Pagination><MedlinePgn>6346-6362</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1021/acs.jmedchem.9b00781</ELocationID><Abstract><AbstractText>The 6'-fluorinated aristeromycins were designed as dual-target antiviral compounds aimed at inhibiting both the viral RNA-dependent RNA polymerase (RdRp) and the host cell <i>S</i>-adenosyl-l-homocysteine (SAH) hydrolase, which would indirectly target capping of viral RNA. The introduction of a fluorine at the 6'-position enhanced the inhibition of SAH hydrolase and the activity against RNA viruses. The adenosine and <i>N</i><sup>6</sup>-methyladenosine analogues <b>2a-e</b> showed potent inhibition against SAH hydrolase, while only the adenosine derivatives <b>2a-c</b> exhibited potent antiviral activity against all tested RNA viruses such as Middle East respiratory syndrome-coronavirus (MERS-CoV), severe acute respiratory syndrome-coronavirus, chikungunya virus, and/or Zika virus. 6',6'-Difluoroaristeromycin (<b>2c</b>) showed the strongest antiviral effect for MERS-CoV, with a ∼2.5 log reduction in infectious progeny titer in viral load reduction assay. The phosphoramidate prodrug <b>3a</b> also demonstrated potent broad-spectrum antiviral activity, possibly by inhibiting the viral RdRp. This study shows that 6'-fluorinated aristeromycins can serve as starting points for the development of broad-spectrum antiviral agents that target RNA viruses.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Yoon</LastName><ForeName>Ji-Seong</ForeName><Initials>JS</Initials><AffiliationInfo><Affiliation>Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 151-742 , Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Gyudong</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 151-742 , Korea.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>College of Pharmacy and Research Institute of Drug Development , Chonnam National University , Gwangju 500-757 , Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jarhad</LastName><ForeName>Dnyandev B</ForeName><Initials>DB</Initials><AffiliationInfo><Affiliation>Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 151-742 , Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Hong-Rae</ForeName><Initials>HR</Initials><AffiliationInfo><Affiliation>Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 151-742 , Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shin</LastName><ForeName>Young-Sup</ForeName><Initials>YS</Initials><AffiliationInfo><Affiliation>Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 151-742 , Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Qu</LastName><ForeName>Shuhao</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 151-742 , Korea.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>College of Pharmaceutical Engineering , Henan University of Animal Husbandry and Economy , Zhengzhou , 450046 , China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sahu</LastName><ForeName>Pramod K</ForeName><Initials>PK</Initials><AffiliationInfo><Affiliation>Future Medicine Co., Ltd. , Seoul 06665 , Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Hea Ok</ForeName><Initials>HO</Initials><AffiliationInfo><Affiliation>Future Medicine Co., Ltd. , Seoul 06665 , Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lee</LastName><ForeName>Hyuk Woo</ForeName><Initials>HW</Initials><AffiliationInfo><Affiliation>Future Medicine Co., Ltd. , Seoul 06665 , Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Su Bin</ForeName><Initials>SB</Initials><AffiliationInfo><Affiliation>College of Pharmacy , Ewha Womans University , Seoul 120-750 , Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kong</LastName><ForeName>Yun Jeong</ForeName><Initials>YJ</Initials><AffiliationInfo><Affiliation>College of Pharmacy , Ewha Womans University , Seoul 120-750 , Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chang</LastName><ForeName>Tong-Shin</ForeName><Initials>TS</Initials><AffiliationInfo><Affiliation>Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 151-742 , Korea.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>College of Pharmacy , Ewha Womans University , Seoul 120-750 , Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ogando</LastName><ForeName>Natacha S</ForeName><Initials>NS</Initials><AffiliationInfo><Affiliation>Department of Medical Microbiology , Leiden University Medical Center , Albinusdreef 2 , 2333ZA Leiden , The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kovacikova</LastName><ForeName>Kristina</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Medical Microbiology , Leiden University Medical Center , Albinusdreef 2 , 2333ZA Leiden , The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Snijder</LastName><ForeName>Eric J</ForeName><Initials>EJ</Initials><AffiliationInfo><Affiliation>Department of Medical Microbiology , Leiden University Medical Center , Albinusdreef 2 , 2333ZA Leiden , The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Posthuma</LastName><ForeName>Clara C</ForeName><Initials>CC</Initials><AffiliationInfo><Affiliation>Department of Medical Microbiology , Leiden University Medical Center , Albinusdreef 2 , 2333ZA Leiden , The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>van Hemert</LastName><ForeName>Martijn J</ForeName><Initials>MJ</Initials><AffiliationInfo><Affiliation>Department of Medical Microbiology , Leiden University Medical Center , Albinusdreef 2 , 2333ZA Leiden , The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jeong</LastName><ForeName>Lak Shin</ForeName><Initials>LS</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-3441-707X</Identifier><AffiliationInfo><Affiliation>Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 151-742 , Korea.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate 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IdType="pmc">PMC7075649</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>J Med Chem. 2015 Jun 25;58(12):5108-20</Citation><ArticleIdList><ArticleId IdType="pubmed">26010585</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Org Chem. 2011 Oct 21;76(20):8311-9</Citation><ArticleIdList><ArticleId IdType="pubmed">21916475</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Med Chem. 2018 Mar 22;61(6):2211-2226</Citation><ArticleIdList><ArticleId IdType="pubmed">28792763</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Nat Rev Microbiol. 2010 Jul;8(7):491-500</Citation><ArticleIdList><ArticleId IdType="pubmed">20551973</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Cureus. 2018 Jul 22;10(7):e3025</Citation><ArticleIdList><ArticleId IdType="pubmed">30254814</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Antibiot (Tokyo). 1968 Apr;21(4):255-63</Citation><ArticleIdList><ArticleId IdType="pubmed">5671989</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Sci Rep. 2017 May 24;7(1):2368</Citation><ArticleIdList><ArticleId IdType="pubmed">28539654</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>New Microbiol. 2013 Jul;36(3):211-27</Citation><ArticleIdList><ArticleId IdType="pubmed">23912863</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Biochem Biophys Methods. 2006 Jun 30;67(2-3):131-40</Citation><ArticleIdList><ArticleId IdType="pubmed">16516302</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Respirology. 2003 Nov;8 Suppl:S9-14</Citation><ArticleIdList><ArticleId IdType="pubmed">15018127</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Med Chem. 1988 Sep;31(9):1798-804</Citation><ArticleIdList><ArticleId IdType="pubmed">2842505</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Med Chem. 2011 Feb 24;54(4):930-8</Citation><ArticleIdList><ArticleId IdType="pubmed">21226494</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>ChemMedChem. 2009 Nov;4(11):1779-91</Citation><ArticleIdList><ArticleId IdType="pubmed">19760699</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Med Chem. 2001 Nov 8;44(23):3985-93</Citation><ArticleIdList><ArticleId IdType="pubmed">11689085</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Med Chem. 2006 Nov 30;49(24):7215-26</Citation><ArticleIdList><ArticleId IdType="pubmed">17125274</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Asian Pac J Trop Med. 2014 Dec;7(12):925-32</Citation><ArticleIdList><ArticleId IdType="pubmed">25479619</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>PLoS One. 2012;7(3):e32857</Citation><ArticleIdList><ArticleId IdType="pubmed">22412934</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Med Chem. 2014 Feb 27;57(4):1531-42</Citation><ArticleIdList><ArticleId IdType="pubmed">24471998</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Annu Rev Virol. 2017 Sep 29;4(1):413-427</Citation><ArticleIdList><ArticleId IdType="pubmed">28637387</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Clin Virol. 2016 Nov;84:53-58</Citation><ArticleIdList><ArticleId IdType="pubmed">27721110</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Med Chem. 1999 Feb 11;42(3):393-9</Citation><ArticleIdList><ArticleId IdType="pubmed">9986709</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Virol. 2017 Feb 14;91(5):</Citation><ArticleIdList><ArticleId IdType="pubmed">28031359</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Biochem Pharmacol. 1986 Nov 15;35(22):4106-9</Citation><ArticleIdList><ArticleId IdType="pubmed">3022752</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Lancet Infect Dis. 2018 Aug;18(8):e217-e227</Citation><ArticleIdList><ArticleId IdType="pubmed">29680581</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Bacteriol Rev. 1971 Sep;35(3):235-41</Citation><ArticleIdList><ArticleId IdType="pubmed">4329869</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Cell Biochem Biophys. 2000;33(2):101-25</Citation><ArticleIdList><ArticleId IdType="pubmed">11325033</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Med Chem. 1998 Jul 2;41(14):2572-8</Citation><ArticleIdList><ArticleId IdType="pubmed">9651161</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Mol Pharmacol. 1986 Apr;29(4):383-90</Citation><ArticleIdList><ArticleId IdType="pubmed">3702857</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Antiviral Res. 2012 Oct;96(1):21-31</Citation><ArticleIdList><ArticleId IdType="pubmed">22841701</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Semin Respir Crit Care Med. 2009 Feb;30(1):67-85</Citation><ArticleIdList><ArticleId IdType="pubmed">19199189</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>mBio. 2012 Nov 20;3(6):</Citation><ArticleIdList><ArticleId IdType="pubmed">23170002</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Med Chem. 2010 Oct 14;53(19):7202-18</Citation><ArticleIdList><ArticleId IdType="pubmed">20845908</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Clin Microbiol Rev. 2016 Jul;29(3):487-524</Citation><ArticleIdList><ArticleId IdType="pubmed">27029595</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Org Chem. 2001 Sep 21;66(19):6490-4</Citation><ArticleIdList><ArticleId IdType="pubmed">11559205</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Med Chem. 1993 Apr 16;36(8):1048-52</Citation><ArticleIdList><ArticleId IdType="pubmed">8478904</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Nat Rev Drug Discov. 2013 Jun;12(6):447-64</Citation><ArticleIdList><ArticleId IdType="pubmed">23722347</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Med Chem. 2005 May 19;48(10):3504-15</Citation><ArticleIdList><ArticleId IdType="pubmed">15887959</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Nat Rev Microbiol. 2011 Dec 05;10(1):51-65</Citation><ArticleIdList><ArticleId IdType="pubmed">22138959</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Med Chem. 2003 Jan 16;46(2):201-3</Citation><ArticleIdList><ArticleId IdType="pubmed">12519056</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Emerg Infect Dis. 2015 Feb;21(2):359-61</Citation><ArticleIdList><ArticleId IdType="pubmed">25625872</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Org Lett. 2017 Nov 3;19(21):5732-5735</Citation><ArticleIdList><ArticleId IdType="pubmed">29028350</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Virol. 2016 Jul 27;90(16):7248-7256</Citation><ArticleIdList><ArticleId IdType="pubmed">27252528</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Antimicrob Agents Chemother. 2014 Aug;58(8):4875-84</Citation><ArticleIdList><ArticleId IdType="pubmed">24841269</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Med Chem. 1991 May;34(5):1521-30</Citation><ArticleIdList><ArticleId IdType="pubmed">2033576</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Lancet. 2015 Sep 5;386(9997):995-1007</Citation><ArticleIdList><ArticleId IdType="pubmed">26049252</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Trends Biochem Sci. 2004 Aug;29(8):436-44</Citation><ArticleIdList><ArticleId IdType="pubmed">15362228</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>PLoS One. 2013 Aug 01;8(8):e71047</Citation><ArticleIdList><ArticleId IdType="pubmed">23936484</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Antiviral Res. 2017 Jul;143:230-236</Citation><ArticleIdList><ArticleId IdType="pubmed">28461070</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Nat Rev Drug Discov. 2002 Jan;1(1):13-25</Citation><ArticleIdList><ArticleId IdType="pubmed">12119605</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Science. 2002 May 17;296(5571):1270-3</Citation><ArticleIdList><ArticleId IdType="pubmed">12016304</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Nucleosides Nucleotides Nucleic Acids. 2003 May-Aug;22(5-8):589-92</Citation><ArticleIdList><ArticleId IdType="pubmed">14565234</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>MMWR Morb Mortal Wkly Rep. 2016 Apr 01;65(12):323-5</Citation><ArticleIdList><ArticleId IdType="pubmed">27032078</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Med Chem. 1992 May 15;35(10):1782-91</Citation><ArticleIdList><ArticleId IdType="pubmed">1588558</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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