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

  • Cell Res. 2021 Jan;31(1):17-24. doi: 10.1038/s41422-020-00450-0.
Gan Wang   #  1 ,  Meng-Li Yang   #  2 ,  Zi-Lei Duan   #  1 ,  Feng-Liang Liu   #  1 ,  Lin Jin   #  1 ,  Cheng-Bo Long  1 ,  Min Zhang  1  3 ,  Xiao-Peng Tang  1  4 ,  Ling Xu  1 ,  Ying-Chang Li  1 ,  Peter Muiruri Kamau  1  3  4 ,  Lian Yang  5 ,  Hong-Qi Liu  2 ,  Jing-Wen Xu  2 ,  Jie-Kai Chen  6 ,  Yong-Tang Zheng  7  8 ,  Xiao-Zhong Peng  9 ,  Ren Lai  10  11  12  13
Affiliations
  • 1. 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.
  • 2. Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Kunming, Yunnan, 650031, China.
  • 3. University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 4. Sino-African Joint Research Center, Chinese Academy of Science, Wuhan, Hubei, 430074, China.
  • 5. Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan, 650201, China.
  • 6. Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong, 510530, China.
  • 7. 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. [email protected].
  • 8. Kunming National High-level Biosafety Research Center for Non-human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology Chinese Academic of Sciences, Kunming, Yunnan, 650107, China. [email protected].
  • 9. Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Kunming, Yunnan, 650031, China. [email protected].
  • 10. 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. [email protected].
  • 11. Sino-African Joint Research Center, Chinese Academy of Science, Wuhan, Hubei, 430074, China. [email protected].
  • 12. Kunming National High-level Biosafety Research Center for Non-human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology Chinese Academic of Sciences, Kunming, Yunnan, 650107, China. [email protected].
  • 13. Institutes for Drug Discovery and Development, Chinese Academy of Sciences, Shanghai, 201203, China. [email protected].
  • # Contributed equally.
PMID: 33262453 DOI: 10.1038/s41422-020-00450-0
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 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.

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