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.
【저자키워드】 SARS-CoV-2, Drug discovery, 【초록키워드】 COVID-19, Treatment, Arbidol, TMPRSS2, Coronaviruses, coronavirus, therapy, Chloroquine, Repurposed drugs, Antiviral, SARS-CoV, hamsters, peptide, SARS-CoV-2 virus, in vitro, COVID-19 treatment, Repurposed drug, Viral, cells, mice, viral replication, virus entry, pathway, Endosomal acidification, camostat, hamster, umifenovir, in vivo, inhibitor, SARS-CoV-2 replication, cocktail, Combination, Endocytic pathway, drug combination, entry pathway, TMPRSS2 inhibitor, treating COVID-19, today, treatment trials, approach, effective, ENhance, identify, significantly, inhibit, suppresse, suppress, inhibiting, inhibit SARS-CoV-2, treatment trial, 【제목키워드】 Repurposed drug, entry pathway, inhibit, Cross-linking,