Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Kunming Primate Research Center, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Kunming, Yunnan, 650107, China.
Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Kunming, Yunnan, 650031, China.
Cell Res. 2021 Jan;31(1):17-24. doi: 10.1038/s41422-020-00450-0. Epub 2020 Dec 1.
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 EC 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发大流行。然而，目前尚无有效的药物或疫苗可用于治疗或预防由此导致的 2019 年冠状病毒病（COVID-19）。在这里，我们报告了我们基于 FDA 批准的肽药物库的虚拟筛选，结合体外和体内抗病毒功能测定，发现了一种有前途的抗 COVID-19 药物候选物，即脂糖肽抗生素达巴万星。我们的结果表明，达巴万星与人血管紧张素转换酶 2（ACE2）具有高亲和力，从而阻断其与 SARS-CoV-2 刺突蛋白的相互作用。此外，达巴万星可有效预防 Vero E6 细胞中 SARS-CoV-2 的复制，EC 值约为 12 nM。在小鼠和恒河猴模型中，达巴万星的给药显著抑制了 SARS-CoV-2 感染引起的病毒复制和组织病理学损伤。鉴于其在先前的临床试验中表现出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有前途的抗 COVID-19 药物候选物。
