Synthesis and Biological Evaluation of Umifenovir Analogues as Anti-SARS-CoV-2 Agents

The unprecedented novel coronavirus disease 2019 (COVID-19) pandemic is a threat to global health and the economy. Since the outbreak of COVID-19, great effort has been made to reposition existing drugs to shorten development timelines, in addition to vaccine development and drug discovery campaigns. Umifenovir is a broad-spectrum antiviral agent used to treat influenza in China and Russia and is currently undergoing clinical trials for the treatment of COVID-19. In this article, the synthesis of umifenovir analogues and their biological evaluation are reported. The inhibitory activities of analogues against the binding of the spike glycoprotein (S-protein) of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to the ACE2 receptor, which is a possible mode of action for umifenovir to inhibit viral infection, were investigated.