Discovery of Pre-Existing Drugs that Suppress the Replication of SARS-CoV-2 in Vitro

SARS-CoV-2, the causative agent of coronavirus disease 19 (COVID 19), is responsible for the ongoing pandemic but still lacks approved antivirals. Repurposing pre-existing FDA approved drugs presents a rapid approach for new therapeutic options. In the present study, we report that three pre-existing FDA-approved drugs, i.e., vapreotide, grazoprevir, and simeprevir, inhibit the replication of SARS-CoV-2 in cells. The E50 values of vapreotide, grazoprevir, and simeprevir against SARS-CoV-2 in Vero E6 cells was 3.98 ± 0.35 μM, 2.08 ± 0.13 μM, and 1.41 ± 0.12 μM, respectively. In vitro biochemical experiments further revealed that vapreotide, grazoprevir, and simeprevir efficiently inhibits the unwinding activity of the Nsp13 helicase of SARS-CoV-2 with IC50 values of ⁓10, ⁓2.5, and ⁓1.25 µM, respectively, providing signs for understanding their antiviral mechanism of action. Given their good safety profiles in their original indications, our study offices new insights in repurposing these drugs alone or in combination with other antivirals in the global fighting against SARS-CoV-2. Funding: This work was financially supported by the Youth Innovation Promotion Association CAS (to H.Y.), and the National Natural Science Foundation of China (No. 31770192 and No. 32070187 to H.Y.). Conflict of Interest: The authors declare no competing interests.