Design, synthesis, and biological evaluation of dithiocarbamate derivatives as SARS-CoV-2 Mpro inhibitors

Abstract

SARS-CoV-2 continues to mutate, spread, and impact public health and daily life. The main protease (M^pro) is essential for the replication and maturation of SARS-CoV-2, making it an ideal target for anti-coronaviral drug discovery and development due to its high conservation and lack of homologous proteases in humans. Herein, we designed and synthesized a series of dithiocarbamate derivatives as potent SARS-CoV-2 M^pro inhibitors. Notably, compound L2 exhibited an IC₅₀ value of 9.1 ± 2.0 nM against SARS-CoV-2 M^pro, underscoring its potential as a promising candidate for anti-coronaviral therapy and justifying further research and development.