Selective Targeting of Virus Replication by Proton Pump Inhibitors
Identifieur interne : 000056 ( Main/Exploration ); précédent : 000055; suivant : 000057Selective Targeting of Virus Replication by Proton Pump Inhibitors
Auteurs : Susan M. Watanabe [États-Unis] ; Lorna S. Ehrlich [États-Unis] ; Madeleine Strickland [États-Unis] ; Xiaofan Li [États-Unis] ; Veronica Soloveva [États-Unis] ; Arthur J. Goff [États-Unis] ; Charles B. Stauft [États-Unis] ; Sumita Bhaduri-Mcintosh [États-Unis] ; Nico Tjandra [États-Unis] ; Carol Carter [États-Unis]Source :
- Scientific Reports [ 2045-2322 ] ; 2020.
Abstract
Two proton pump inhibitors, tenatoprazole and esomeprazole, were previously shown to inhibit HIV-1 egress by blocking the interaction between Tsg101, a member of the ESCRT-I complex, and ubiquitin. Here, we deepen our understanding of prazole budding inhibition by studying a range of viruses in the presence of tenatoprazole. Furthermore, we investigate the relationship between the chemistry of prodrug activation and HIV-1 inhibition for diverse prazoles currently on the market. We report that tenatoprazole is capable of inhibiting the replication of members of the enveloped filo, alpha, and herpes virus families but not the flavivirus group and not the non-enveloped poliovirus. Another key finding is that prazole prodrugs must be activated inside the cell, while their rate of activation
Url:
DOI: 10.1038/s41598-020-60544-y
PubMed: 32132561
PubMed Central: 7055211
Affiliations:
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Ehrlich</name><affiliation wicri:level="2"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2216 9681</institution-id><institution-id institution-id-type="GRID">grid.36425.36</institution-id><institution>Department of Microbiology and Immunology,</institution><institution>Stony Brook University,</institution></institution-wrap>Stony Brook, NY 11794-5222 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Stony Brook</wicri:cityArea></affiliation></author><author><name sortKey="Strickland, Madeleine" sort="Strickland, Madeleine" uniqKey="Strickland M" first="Madeleine" last="Strickland">Madeleine Strickland</name><affiliation wicri:level="2"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2293 4638</institution-id><institution-id institution-id-type="GRID">grid.279885.9</institution-id><institution>Laboratory of Molecular Biophysics,</institution><institution>National Heart, Lung, and Blood Institute, National Institutes of Health,</institution></institution-wrap>Bethesda, MD 20892 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Bethesda</wicri:cityArea></affiliation></author><author><name sortKey="Li, Xiaofan" sort="Li, Xiaofan" uniqKey="Li X" first="Xiaofan" last="Li">Xiaofan Li</name><affiliation wicri:level="2"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 8091</institution-id><institution-id institution-id-type="GRID">grid.15276.37</institution-id><institution>Department of Pediatrics,</institution><institution>Division of Infectious Diseases and Department of Molecular Genetics and Microbiology, University of Florida,</institution></institution-wrap>Gainesville, FL 32610 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Floride</region></placeName><wicri:cityArea>Gainesville</wicri:cityArea></affiliation></author><author><name sortKey="Soloveva, Veronica" sort="Soloveva, Veronica" uniqKey="Soloveva V" first="Veronica" last="Soloveva">Veronica Soloveva</name><affiliation wicri:level="2"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0666 4455</institution-id><institution-id institution-id-type="GRID">grid.416900.a</institution-id><institution>U.S. Army Medical Research Institute of Infectious Diseases,</institution></institution-wrap>Frederick, MD 21702-5011 USA</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Frederick</wicri:cityArea></affiliation></author><author><name sortKey="Goff, Arthur J" sort="Goff, Arthur J" uniqKey="Goff A" first="Arthur J." last="Goff">Arthur J. 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Here, we deepen our understanding of prazole budding inhibition by studying a range of viruses in the presence of tenatoprazole. Furthermore, we investigate the relationship between the chemistry of prodrug activation and HIV-1 inhibition for diverse prazoles currently on the market. We report that tenatoprazole is capable of inhibiting the replication of members of the enveloped filo, alpha, and herpes virus families but not the flavivirus group and not the non-enveloped poliovirus. Another key finding is that prazole prodrugs must be activated inside the cell, while their rate of activation <italic>in vitro</italic> correlated to their efficacy in cells. Our study lays the groundwork for future efforts to repurpose prazole-based compounds as antivirals that are both broad-spectrum and selective in nature.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Votteler, J" uniqKey="Votteler J">J Votteler</name></author><author><name sortKey="Sundquist, Wi" uniqKey="Sundquist W">WI Sundquist</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hurley, Jh" uniqKey="Hurley J">JH Hurley</name></author><author><name sortKey="Cada, Ak" uniqKey="Cada A">AK Cada</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Strickland, M" uniqKey="Strickland M">M Strickland</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ahmed, I" uniqKey="Ahmed I">I Ahmed</name></author><author><name sortKey="Akram, Z" uniqKey="Akram Z">Z Akram</name></author><author><name sortKey="Iqbal, Hmn" uniqKey="Iqbal H">HMN 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Bi</name></author><author><name sortKey="Might, M" uniqKey="Might M">M Might</name></author><author><name sortKey="Vankayalapati, H" uniqKey="Vankayalapati H">H Vankayalapati</name></author><author><name sortKey="Kuberan, B" uniqKey="Kuberan B">B Kuberan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Williamson, Mp" uniqKey="Williamson M">MP Williamson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Delaglio, F" uniqKey="Delaglio F">F Delaglio</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vranken, Wf" uniqKey="Vranken W">WF Vranken</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stauft, Cb" uniqKey="Stauft C">CB Stauft</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Abbink, P" uniqKey="Abbink P">P Abbink</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Floride</li><li>Maryland</li><li>État de New York</li></region></list><tree><country name="États-Unis"><region name="État de New York"><name sortKey="Watanabe, Susan M" sort="Watanabe, Susan M" uniqKey="Watanabe S" first="Susan M." last="Watanabe">Susan M. Watanabe</name></region><name sortKey="Bhaduri Mcintosh, Sumita" sort="Bhaduri Mcintosh, Sumita" uniqKey="Bhaduri Mcintosh S" first="Sumita" last="Bhaduri-Mcintosh">Sumita Bhaduri-Mcintosh</name><name sortKey="Carter, Carol" sort="Carter, Carol" uniqKey="Carter C" first="Carol" last="Carter">Carol Carter</name><name sortKey="Ehrlich, Lorna S" sort="Ehrlich, Lorna S" uniqKey="Ehrlich L" first="Lorna S." last="Ehrlich">Lorna S. Ehrlich</name><name sortKey="Goff, Arthur J" sort="Goff, Arthur J" uniqKey="Goff A" first="Arthur J." last="Goff">Arthur J. Goff</name><name sortKey="Li, Xiaofan" sort="Li, Xiaofan" uniqKey="Li X" first="Xiaofan" last="Li">Xiaofan Li</name><name sortKey="Soloveva, Veronica" sort="Soloveva, Veronica" uniqKey="Soloveva V" first="Veronica" last="Soloveva">Veronica Soloveva</name><name sortKey="Stauft, Charles B" sort="Stauft, Charles B" uniqKey="Stauft C" first="Charles B." last="Stauft">Charles B. Stauft</name><name sortKey="Strickland, Madeleine" sort="Strickland, Madeleine" uniqKey="Strickland M" first="Madeleine" last="Strickland">Madeleine Strickland</name><name sortKey="Tjandra, Nico" sort="Tjandra, Nico" uniqKey="Tjandra N" first="Nico" last="Tjandra">Nico Tjandra</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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