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Article: Cross-linking peptide and repurposed drugs inhibit both entry pathways of SARS-CoV-2

TitleCross-linking peptide and repurposed drugs inhibit both entry pathways of SARS-CoV-2
Authors
Issue Date2021
PublisherNature Research: Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html
Citation
Nature Communications, 2021, v. 12, p. article no. 1517 How to Cite?
AbstractUp to date, effective antivirals have not been widely available for treating COVID-19. In this study, we identify a dual-functional cross-linking peptide 8P9R which can inhibit the two entry pathways (endocytic pathway and TMPRSS2-mediated surface pathway) of SARS-CoV-2 in cells. The endosomal acidification inhibitors (8P9R and chloroquine) can synergistically enhance the activity of arbidol, a spike-ACE2 fusion inhibitor, against SARS-CoV-2 and SARS-CoV in cells. In vivo studies indicate that 8P9R or the combination of repurposed drugs (umifenovir also known as arbidol, chloroquine and camostat which is a TMPRSS2 inhibitor), simultaneously interfering with the two entry pathways of coronaviruses, can significantly suppress SARS-CoV-2 replication in hamsters and SARS-CoV in mice. Here, we use drug combination (arbidol, chloroquine, and camostat) and a dual-functional 8P9R to demonstrate that blocking the two entry pathways of coronavirus can be a promising and achievable approach for inhibiting SARS-CoV-2 replication in vivo. Cocktail therapy of these drug combinations should be considered in treatment trials for COVID-19.
Persistent Identifierhttp://hdl.handle.net/10722/304717
ISSN
2023 Impact Factor: 14.7
2023 SCImago Journal Rankings: 4.887
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhao, H-
dc.contributor.authorTo, KKW-
dc.contributor.authorLam, H-
dc.contributor.authorZhou, X-
dc.contributor.authorChan, JFW-
dc.contributor.authorPeng, Z-
dc.contributor.authorLee, ACY-
dc.contributor.authorCai, J-
dc.contributor.authorChan, WM-
dc.contributor.authorIp, JD-
dc.contributor.authorChan, CCS-
dc.contributor.authorYeung, ML-
dc.contributor.authorZhang, AJ-
dc.contributor.authorChu, AWH-
dc.contributor.authorJiang, S-
dc.contributor.authorYuen, KY-
dc.date.accessioned2021-10-05T02:34:09Z-
dc.date.available2021-10-05T02:34:09Z-
dc.date.issued2021-
dc.identifier.citationNature Communications, 2021, v. 12, p. article no. 1517-
dc.identifier.issn2041-1723-
dc.identifier.urihttp://hdl.handle.net/10722/304717-
dc.description.abstractUp to date, effective antivirals have not been widely available for treating COVID-19. In this study, we identify a dual-functional cross-linking peptide 8P9R which can inhibit the two entry pathways (endocytic pathway and TMPRSS2-mediated surface pathway) of SARS-CoV-2 in cells. The endosomal acidification inhibitors (8P9R and chloroquine) can synergistically enhance the activity of arbidol, a spike-ACE2 fusion inhibitor, against SARS-CoV-2 and SARS-CoV in cells. In vivo studies indicate that 8P9R or the combination of repurposed drugs (umifenovir also known as arbidol, chloroquine and camostat which is a TMPRSS2 inhibitor), simultaneously interfering with the two entry pathways of coronaviruses, can significantly suppress SARS-CoV-2 replication in hamsters and SARS-CoV in mice. Here, we use drug combination (arbidol, chloroquine, and camostat) and a dual-functional 8P9R to demonstrate that blocking the two entry pathways of coronavirus can be a promising and achievable approach for inhibiting SARS-CoV-2 replication in vivo. Cocktail therapy of these drug combinations should be considered in treatment trials for COVID-19.-
dc.languageeng-
dc.publisherNature Research: Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html-
dc.relation.ispartofNature Communications-
dc.rightsNature Communications. Copyright © Nature Research: Fully open access journals.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleCross-linking peptide and repurposed drugs inhibit both entry pathways of SARS-CoV-2-
dc.typeArticle-
dc.identifier.emailZhao, H: hjzhao13@hku.hk-
dc.identifier.emailTo, KKW: kelvinto@hku.hk-
dc.identifier.emailLam, H: nayioh16@hku.hk-
dc.identifier.emailChan, JFW: jfwchan@hku.hk-
dc.identifier.emailPeng, Z: pz0929@hku.hk-
dc.identifier.emailLee, ACY: cyalee@hku.hk-
dc.identifier.emailCai, J: caijuice@hku.hk-
dc.identifier.emailChan, WM: mbally@hku.hk-
dc.identifier.emailChan, CCS: cschan@hku.hk-
dc.identifier.emailYeung, ML: pmlyeung@hku.hk-
dc.identifier.emailZhang, AJ: zhangajx@hkucc.hku.hk-
dc.identifier.emailChu, AWH: awhchu@hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.authorityZhao, H=rp02653-
dc.identifier.authorityTo, KKW=rp01384-
dc.identifier.authorityChan, JFW=rp01736-
dc.identifier.authorityYeung, ML=rp01402-
dc.identifier.authorityZhang, AJ=rp00413-
dc.identifier.authorityYuen, KY=rp00366-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41467-021-21825-w-
dc.identifier.scopuseid_2-s2.0-85102276584-
dc.identifier.hkuros326095-
dc.identifier.volume12-
dc.identifier.spagearticle no. 1517-
dc.identifier.epagearticle no. 1517-
dc.identifier.isiWOS:000627829600003-
dc.publisher.placeUnited Kingdom-

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