1,3-Diphenylurea derivatives inhibit cellular entry of influenza A virus and SARS-CoV-2

Abstract Influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are highly contagious pathogens that cause severe respiratory illnesses, often leading to hospitalization and death. Rapid emergence of mutant viral strains and waning immunity in the vaccinated individuals represent major challenges in the global fight against both the viruses. Complementing vaccine protection, a search for new therapeutic agents, effective against the existing and emerging viral strains, is an urgent priority. In this study, we identified 1,3-diphenylurea derivatives (DPUDs) as a new class of potential antiviral agents that robustly inhibited infections by different strains of IAV and SARS-CoV-2. Our study revealed, DPUDs primarily target the host cell entry of the viruses. That DPUDs affect the host processes exploited by IAV and SARS-CoV-2 for cellular entry, they are expected to be broadly effective against other related viruses that co-opt the same entry pathways.