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

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.

Automated summary

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.