1. Dalbavancin binds ACE2 to block its interaction with SARS-CoV-2 spike protein and is effective in inhibiting SARS-CoV-2 infection in animal models
- Author
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Wang, Gan, Yang, Meng-Li, Duan, Zi-Lei, Liu, Feng-Liang, Jin, Lin, Long, Cheng-Bo, Zhang, Min, Tang, Xiao-Peng, Xu, Ling, Li, Ying-Chang, Kamau, Peter Muiruri, Yang, Lian, Liu, Hong-Qi, Xu, Jing-Wen, Chen, Jie-Kai, Zheng, Yong-Tang, Peng, Xiao-Zhong, and Lai, Ren
- Abstract
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 EC50of ~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.
- Published
- 2021
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