Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro
Identifieur interne : 000313 ( 2020/Analysis ); précédent : 000312; suivant : 000314Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro
Auteurs : Ka-Tim Choy [République populaire de Chine] ; Alvina Yin-Lam Wong [République populaire de Chine] ; Prathanporn Kaewpreedee [République populaire de Chine] ; Sin Fun Sia [République populaire de Chine] ; Dongdong Chen [République populaire de Chine] ; Kenrie Pui Yan Hui [République populaire de Chine] ; Daniel Ka Wing Chu [République populaire de Chine] ; Michael Chi Wai Chan [République populaire de Chine] ; Peter Pak-Hang Cheung [République populaire de Chine] ; Xuhui Huang [République populaire de Chine] ; Malik Peiris [République populaire de Chine] ; Hui-Ling Yen [République populaire de Chine]Source :
- Antiviral Research [ 0166-3542 ] ; 2020.
Abstract
An escalating pandemic by the novel SARS-CoV-2 virus is impacting global health and effective therapeutic options are urgently needed. We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evaluation in clinical trials for SARS-CoV-2 patients. We report the antiviral effect of remdesivir, lopinavir, homorringtonine, and emetine against SARS-CoV-2 virus in Vero E6 cells with the estimated 50% effective concentration at 23.15 μM, 26.63 μM, 2.55 μM and 0.46 μM, respectively. Ribavirin or favipiravir that are currently evaluated under clinical trials showed no inhibition at 100 μM. Synergy between remdesivir and emetine was observed, and remdesivir at 6.25 μM in combination with emetine at 0.195 μM may achieve 64.9% inhibition in viral yield. Combinational therapy may help to reduce the effective concentration of compounds below the therapeutic plasma concentrations and provide better clinical benefits.
Url:
DOI: 10.1016/j.antiviral.2020.104786
PubMed: 32251767
PubMed Central: 7127386
Affiliations:
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University of Hong Kong, Hong Kong SAR, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Wong, Alvina Yin Lam" sort="Wong, Alvina Yin Lam" uniqKey="Wong A" first="Alvina Yin-Lam" last="Wong">Alvina Yin-Lam Wong</name><affiliation wicri:level="1"><nlm:aff id="aff1">School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Kaewpreedee, Prathanporn" sort="Kaewpreedee, Prathanporn" uniqKey="Kaewpreedee P" first="Prathanporn" last="Kaewpreedee">Prathanporn Kaewpreedee</name><affiliation wicri:level="1"><nlm:aff id="aff1">School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Sia, Sin Fun" sort="Sia, Sin Fun" uniqKey="Sia S" first="Sin Fun" last="Sia">Sin Fun Sia</name><affiliation wicri:level="1"><nlm:aff id="aff1">School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Dongdong" sort="Chen, Dongdong" uniqKey="Chen D" first="Dongdong" last="Chen">Dongdong Chen</name><affiliation wicri:level="1"><nlm:aff id="aff1">School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Hui, Kenrie Pui Yan" sort="Hui, Kenrie Pui Yan" uniqKey="Hui K" first="Kenrie Pui Yan" last="Hui">Kenrie Pui Yan Hui</name><affiliation wicri:level="1"><nlm:aff id="aff1">School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Chu, Daniel Ka Wing" sort="Chu, Daniel Ka Wing" uniqKey="Chu D" first="Daniel Ka Wing" last="Chu">Daniel Ka Wing Chu</name><affiliation wicri:level="1"><nlm:aff id="aff1">School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Chan, Michael Chi Wai" sort="Chan, Michael Chi Wai" uniqKey="Chan M" first="Michael Chi Wai" last="Chan">Michael Chi Wai Chan</name><affiliation wicri:level="1"><nlm:aff id="aff1">School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Cheung, Peter Pak Hang" sort="Cheung, Peter Pak Hang" uniqKey="Cheung P" first="Peter Pak-Hang" last="Cheung">Peter Pak-Hang Cheung</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Chemistry, Hong Kong University of Science and Technology, Hong Kong SAR, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Chemistry, Hong Kong University of Science and Technology, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Huang, Xuhui" sort="Huang, Xuhui" uniqKey="Huang X" first="Xuhui" last="Huang">Xuhui Huang</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Chemistry, Hong Kong University of Science and Technology, Hong Kong SAR, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Chemistry, Hong Kong University of Science and Technology, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Peiris, Malik" sort="Peiris, Malik" uniqKey="Peiris M" first="Malik" last="Peiris">Malik Peiris</name><affiliation wicri:level="1"><nlm:aff id="aff1">School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author><author><name sortKey="Yen, Hui Ling" sort="Yen, Hui Ling" uniqKey="Yen H" first="Hui-Ling" last="Yen">Hui-Ling Yen</name><affiliation wicri:level="1"><nlm:aff id="aff1">School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR</wicri:regionArea><wicri:noRegion>Hong Kong SAR</wicri:noRegion></affiliation></author></analytic><series><title level="j">Antiviral Research</title><idno type="ISSN">0166-3542</idno><idno type="eISSN">1872-9096</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>An escalating pandemic by the novel SARS-CoV-2 virus is impacting global health and effective therapeutic options are urgently needed. We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evaluation in clinical trials for SARS-CoV-2 patients. We report the antiviral effect of remdesivir, lopinavir, homorringtonine, and emetine against SARS-CoV-2 virus in Vero E6 cells with the estimated 50% effective concentration at 23.15 μM, 26.63 μM, 2.55 μM and 0.46 μM, respectively. Ribavirin or favipiravir that are currently evaluated under clinical trials showed no inhibition at 100 μM. Synergy between remdesivir and emetine was observed, and remdesivir at 6.25 μM in combination with emetine at 0.195 μM may achieve 64.9% inhibition in viral yield. Combinational therapy may help to reduce the effective concentration of compounds below the therapeutic plasma concentrations and provide better clinical benefits.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Agostini, M L" uniqKey="Agostini M">M.L. Agostini</name></author><author><name sortKey="Andres, E L" uniqKey="Andres E">E.L. Andres</name></author><author><name sortKey="Sims, A C" uniqKey="Sims A">A.C. Sims</name></author><author><name sortKey="Graham, R L" uniqKey="Graham R">R.L. Graham</name></author><author><name sortKey="Sheahan, T P" uniqKey="Sheahan T">T.P. Sheahan</name></author><author><name sortKey="Lu, X" uniqKey="Lu X">X. Lu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Andersen, P I" uniqKey="Andersen P">P.I. Andersen</name></author><author><name sortKey="Krpina, K" uniqKey="Krpina K">K. Krpina</name></author><author><name sortKey="Ianevski, A" uniqKey="Ianevski A">A. 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Zhang</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Choy, Ka Tim" sort="Choy, Ka Tim" uniqKey="Choy K" first="Ka-Tim" last="Choy">Ka-Tim Choy</name></noRegion><name sortKey="Chan, Michael Chi Wai" sort="Chan, Michael Chi Wai" uniqKey="Chan M" first="Michael Chi Wai" last="Chan">Michael Chi Wai Chan</name><name sortKey="Chen, Dongdong" sort="Chen, Dongdong" uniqKey="Chen D" first="Dongdong" last="Chen">Dongdong Chen</name><name sortKey="Cheung, Peter Pak Hang" sort="Cheung, Peter Pak Hang" uniqKey="Cheung P" first="Peter Pak-Hang" last="Cheung">Peter Pak-Hang Cheung</name><name sortKey="Chu, Daniel Ka Wing" sort="Chu, Daniel Ka Wing" uniqKey="Chu D" first="Daniel Ka Wing" last="Chu">Daniel Ka Wing Chu</name><name sortKey="Huang, Xuhui" sort="Huang, Xuhui" uniqKey="Huang X" first="Xuhui" last="Huang">Xuhui Huang</name><name sortKey="Hui, Kenrie Pui Yan" sort="Hui, Kenrie Pui Yan" uniqKey="Hui K" first="Kenrie Pui Yan" last="Hui">Kenrie Pui Yan Hui</name><name sortKey="Kaewpreedee, Prathanporn" sort="Kaewpreedee, Prathanporn" uniqKey="Kaewpreedee P" first="Prathanporn" last="Kaewpreedee">Prathanporn Kaewpreedee</name><name sortKey="Peiris, Malik" sort="Peiris, Malik" uniqKey="Peiris M" first="Malik" last="Peiris">Malik Peiris</name><name sortKey="Sia, Sin Fun" sort="Sia, Sin Fun" uniqKey="Sia S" first="Sin Fun" last="Sia">Sin Fun Sia</name><name sortKey="Wong, Alvina Yin Lam" sort="Wong, Alvina Yin Lam" uniqKey="Wong A" first="Alvina Yin-Lam" last="Wong">Alvina Yin-Lam Wong</name><name sortKey="Yen, Hui Ling" sort="Yen, Hui Ling" uniqKey="Yen H" first="Hui-Ling" last="Yen">Hui-Ling Yen</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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