File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Simeprevir Potently Suppresses SARS-CoV-2 Replication and Synergizes with Remdesivir

TitleSimeprevir Potently Suppresses SARS-CoV-2 Replication and Synergizes with Remdesivir
Authors
Issue Date2021
PublisherAmerican Chemical Society: Open Access Titles. The Journal's web site is located at http://pubs.acs.org/journal/acscii
Citation
ACS Central Science, 2021, v. 7 n. 5, p. 792-802 How to Cite?
AbstractThe outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global threat to human health. Using a multidisciplinary approach, we identified and validated the hepatitis C virus (HCV) protease inhibitor simeprevir as an especially promising repurposable drug for treating COVID-19. Simeprevir potently reduces SARS-CoV-2 viral load by multiple orders of magnitude and synergizes with remdesivir in vitro. Mechanistically, we showed that simeprevir not only inhibits the main protease (Mpro) and unexpectedly the RNA-dependent RNA polymerase (RdRp) but also modulates host immune responses. Our results thus reveal the possible anti-SARS-CoV-2 mechanism of simeprevir and highlight the translational potential of optimizing simeprevir as a therapeutic agent for managing COVID-19 and future outbreaks of CoV.
Persistent Identifierhttp://hdl.handle.net/10722/305184
ISSN
2023 Impact Factor: 12.7
2023 SCImago Journal Rankings: 3.722
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLo, HS-
dc.contributor.authorHui, KPY-
dc.contributor.authorLai, HM-
dc.contributor.authorHe, X-
dc.contributor.authorKhan, KS-
dc.contributor.authorKaur, S-
dc.contributor.authorHuang, J-
dc.contributor.authorLi, Z-
dc.contributor.authorChan, AKN-
dc.contributor.authorCheung, HHY-
dc.contributor.authorNg, KC-
dc.contributor.authorHo, JCW-
dc.contributor.authorChen, YW-
dc.contributor.authorMa, B-
dc.contributor.authorCheung, PMH-
dc.contributor.authorShin, D-
dc.contributor.authorWang, K-
dc.contributor.authorLee, MH-
dc.contributor.authorSelisko, B-
dc.contributor.authorEydoux, C-
dc.contributor.authorGuillemot, JC-
dc.contributor.authorCanard, B-
dc.contributor.authorWu, KP-
dc.contributor.authorLiang, PH-
dc.contributor.authorDikic, I-
dc.contributor.authorZuo, Z-
dc.contributor.authorChan, FK-
dc.contributor.authorHui, DSC-
dc.contributor.authorMok, VC-
dc.contributor.authorWong, KB-
dc.contributor.authorMok, CKP-
dc.contributor.authorKo, H-
dc.contributor.authorAik, WS-
dc.contributor.authorChan, MCW-
dc.contributor.authorNg, WL-
dc.date.accessioned2021-10-20T10:05:48Z-
dc.date.available2021-10-20T10:05:48Z-
dc.date.issued2021-
dc.identifier.citationACS Central Science, 2021, v. 7 n. 5, p. 792-802-
dc.identifier.issn2374-7951-
dc.identifier.urihttp://hdl.handle.net/10722/305184-
dc.description.abstractThe outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global threat to human health. Using a multidisciplinary approach, we identified and validated the hepatitis C virus (HCV) protease inhibitor simeprevir as an especially promising repurposable drug for treating COVID-19. Simeprevir potently reduces SARS-CoV-2 viral load by multiple orders of magnitude and synergizes with remdesivir in vitro. Mechanistically, we showed that simeprevir not only inhibits the main protease (Mpro) and unexpectedly the RNA-dependent RNA polymerase (RdRp) but also modulates host immune responses. Our results thus reveal the possible anti-SARS-CoV-2 mechanism of simeprevir and highlight the translational potential of optimizing simeprevir as a therapeutic agent for managing COVID-19 and future outbreaks of CoV.-
dc.languageeng-
dc.publisherAmerican Chemical Society: Open Access Titles. The Journal's web site is located at http://pubs.acs.org/journal/acscii-
dc.relation.ispartofACS Central Science-
dc.rightsThis is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleSimeprevir Potently Suppresses SARS-CoV-2 Replication and Synergizes with Remdesivir-
dc.typeArticle-
dc.identifier.emailHui, KPY: kenrie@hku.hk-
dc.identifier.emailNg, KC: kckachun@hku.hk-
dc.identifier.emailHo, JCW: cwjohn@connect.hku.hk-
dc.identifier.emailChan, MCW: mchan@hku.hk-
dc.identifier.authorityHui, KPY=rp02149-
dc.identifier.authorityChan, MCW=rp00420-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1021/acscentsci.0c01186-
dc.identifier.pmid34075346-
dc.identifier.pmcidPMC8056950-
dc.identifier.scopuseid_2-s2.0-85105116950-
dc.identifier.hkuros327760-
dc.identifier.volume7-
dc.identifier.issue5-
dc.identifier.spage792-
dc.identifier.epage802-
dc.identifier.isiWOS:000657243600013-
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats