Arenaviruses and coronaviruses include several human pathogenic viruses, such as Lassa virus, Lymphocytic choriomeningitis virus (LCMV), SARS-CoV, MERS-CoV, and SARS-CoV-2. Although these viruses belong to different virus families, they possess a common motif, the DED/EDh motif, known as an exonuclease (ExoN) motif. In this study, proof-of-concept studies, in which the DED/EDh motif in these viral proteins, NP for arenaviruses, and nsp14 for coronaviruses, could be a drug target, were performed. Docking simulation studies between two structurally different chemical compounds, ATA and PV6R, and the DED/EDh motifs in these viral proteins indicated that these compounds target DED/EDh motifs. The concentration which exhibited modest cell toxicity was used with these compounds to treat LCMV and SARS-CoV-2 infections in two different cell lines, A549 and Vero 76 cells. Both ATA and PV6R inhibited the post-entry step of LCMV and SARS-CoV-2 infection. These studies strongly suggest that DED/EDh motifs in these viral proteins could be a drug target to combat two distinct viral families, arenaviruses and coronaviruses.
【저자키워드】 SARS-CoV-2, antivirals, Lymphocytic choriomeningitis virus (LCMV), exonuclease (ExoN) motif, DED/EDh motif, 【초록키워드】 Coronaviruses, coronavirus, SARS-CoV, SARS-COV-2 infection, Viral proteins, virus, MERS-CoV, cells, nsp14, drug target, LCMV, arenavirus, compounds, A549, exonuclease, Concentration, cell lines, motifs, Vero, Viral protein, pathogenic viruses, treat, Cell toxicity, motif, Simulation study, performed, was used, include, indicated, inhibited, exhibited, these compound, arenaviruses, Lymphocytic choriomeningitis, 【제목키워드】 Chemical, Compound, targeting, Effect, Choriomeningitis,