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Zhao, Hanjun; To, Kelvin K W; Lam, Hoiyan; Zhou, Xinxin; Chan, Jasper Fuk-Woo; Peng, Zheng; Lee, Andrew C Y; Cai, Jianpiao; Chan, Wan-Mui; Ip, Jonathan Daniel; Chan, Chris Chung-Sing; Yeung, Man Lung; Zhang, Anna Jinxia; Chu, Allen Wing Ho; Jiang, Shibo; Yuen, Kwok-Yung
Nature communications, 03/2021, Letnik: 12, Številka: 1Journal Article
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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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