期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-21825-w
关键词
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资金
- National Program on Key Research Project of China [2020YFA0707500, 2020YFA0707504]
- Shaw Foundation Hong Kong
- Hong Kong Sanatorium Hospital
- Hui Hoy and Chow Sin Lan Charity Fund Limited
- Chan Yin Chuen Memorial Charitable Foundation
- Hong Kong Hainan Commercial Association South China Microbiology Research Fund
- Jessie & George Ho Charitable Foundation
- Perfect Shape Medical Limited
This study identifies a dual-functional cross-linking peptide 8P9R that can inhibit SARS-CoV-2 entry pathways in cells and suppress viral replication in animal models. The combination therapy of drugs like arbidol, chloroquine, and camostat shows promising results in inhibiting SARS-CoV-2 replication, suggesting a potential treatment strategy for COVID-19.
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. Until today effective antivirals for COVID-19 treatment are not widely available. Here, Zhao et al. characterize a dual-functional cross-linking peptide, 8P9R, that can inhibit SARS-CoV-2 virus entry in vitro and suppresses viral replication in vivo in golden Syrian hamster.
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