Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic worldwide. Currently, however, no effective drug or vaccine is available to treat or prevent the resulting coronavirus disease 2019 (COVID-19). Here, we report our discovery of a promising anti-COVID-19 drug candidate, the lipoglycopeptide antibiotic dalbavancin, based on virtual screening of the FDA-approved peptide drug library combined with in vitro and in vivo functional antiviral assays. Our results showed that dalbavancin directly binds to human angiotensin-converting enzyme 2 (ACE2) with high affinity, thereby blocking its interaction with the SARS-CoV-2 spike protein. Furthermore, dalbavancin effectively prevents SARS-CoV-2 replication in Vero E6 cells with an EC₅₀ of ~12 nM. In both mouse and rhesus macaque models, viral replication and histopathological injuries caused by SARS-CoV-2 infection are significantly inhibited by dalbavancin administration. Given its high safety and long plasma half-life (8–10 days) shown in previous clinical trials, our data indicate that dalbavancin is a promising anti-COVID-19 drug candidate.

严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染已在全球范围内引起大流行。然而，目前没有有效的药物或疫苗可用于治疗或预防由此产生的 2019 年冠状病毒病 (COVID-19)。在这里，我们报告了我们发现了一种有前途的抗 COVID-19 候选药物脂糖肽抗生素达巴万星，该药物基于 FDA 批准的肽药物库的虚拟筛选以及体外和体内功能性抗病毒试验。我们的研究结果表明，达巴万星以高亲和力直接与人血管紧张素转换酶 2 (ACE2) 结合，从而阻断其与 SARS-CoV-2 刺突蛋白的相互作用。此外，达巴万星有效地防止 SARS-CoV-2 在 Vero E6 细胞中复制，EC ₅₀约 12 nM。在小鼠和恒河猴模型中，达巴万星显着抑制了由 SARS-CoV-2 感染引起的病毒复制和组织病理学损伤。鉴于先前临床试验中显示的高安全性和较长的血浆半衰期（8-10 天），我们的数据表明达巴万星是一种很有前途的抗 COVID-19 候选药物。