tetano
Editor, Senior Moderator
Nat Commun
. 2021 Mar 9;12(1):1517.
doi: 10.1038/s41467-021-21825-w.
Cross-linking peptide and repurposed drugs inhibit both entry pathways of SARS-CoV-2
Hanjun Zhao[SUP] 1 2 [/SUP], Kelvin K W To[SUP] 1 2 3 [/SUP], Hoiyan Lam[SUP] 2 [/SUP], Xinxin Zhou[SUP] 2 [/SUP], Jasper Fuk-Woo Chan[SUP] 1 2 3 [/SUP], Zheng Peng[SUP] 2 [/SUP], Andrew C Y Lee[SUP] 2 [/SUP], Jianpiao Cai[SUP] 2 [/SUP], Wan-Mui Chan[SUP] 2 [/SUP], Jonathan Daniel Ip[SUP] 2 [/SUP], Chris Chung-Sing Chan[SUP] 2 [/SUP], Man Lung Yeung[SUP] 1 2 3 [/SUP], Anna Jinxia Zhang[SUP] 1 2 [/SUP], Allen Wing Ho Chu[SUP] 2 [/SUP], Shibo Jiang[SUP] 4 [/SUP], Kwok-Yung Yuen[SUP] 5 6 7 [/SUP]
Affiliations
Abstract
Up 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.
. 2021 Mar 9;12(1):1517.
doi: 10.1038/s41467-021-21825-w.
Cross-linking peptide and repurposed drugs inhibit both entry pathways of SARS-CoV-2
Hanjun Zhao[SUP] 1 2 [/SUP], Kelvin K W To[SUP] 1 2 3 [/SUP], Hoiyan Lam[SUP] 2 [/SUP], Xinxin Zhou[SUP] 2 [/SUP], Jasper Fuk-Woo Chan[SUP] 1 2 3 [/SUP], Zheng Peng[SUP] 2 [/SUP], Andrew C Y Lee[SUP] 2 [/SUP], Jianpiao Cai[SUP] 2 [/SUP], Wan-Mui Chan[SUP] 2 [/SUP], Jonathan Daniel Ip[SUP] 2 [/SUP], Chris Chung-Sing Chan[SUP] 2 [/SUP], Man Lung Yeung[SUP] 1 2 3 [/SUP], Anna Jinxia Zhang[SUP] 1 2 [/SUP], Allen Wing Ho Chu[SUP] 2 [/SUP], Shibo Jiang[SUP] 4 [/SUP], Kwok-Yung Yuen[SUP] 5 6 7 [/SUP]
Affiliations
- PMID: 33750821
- DOI: 10.1038/s41467-021-21825-w
Abstract
Up 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.