期刊
CELL RESEARCH
卷 31, 期 1, 页码 17-24出版社
SPRINGERNATURE
DOI: 10.1038/s41422-020-00450-0
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类别
资金
- National Natural Science Foundation of China [81903666, 21761142002, 31600721, 31930015]
- Chinese Academy of Sciences [SAJC201606, ZSTH-034]
- National Key Research and Development Program of China [2020YFC0842000]
- Science and Technology Department of Yunnan Province [2019ZF003, 2019FB103]
- Department of Industry and Information Technology of Yunnan Province [2019-YT-053]
A potential anti-COVID-19 drug candidate, dalbavancin, was discovered based on virtual screening of an FDA-approved peptide drug library and in vitro and in vivo functional antiviral assays. Dalbavancin was found to directly bind to human ACE2, blocking its interaction with the SARS-CoV-2 spike protein and effectively preventing viral replication in cells. Studies in mouse and rhesus macaque models showed that dalbavancin significantly inhibited viral replication and histopathological injuries caused by SARS-CoV-2 infection, indicating its promising potential as an anti-COVID-19 drug candidate.
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 similar to 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.
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