The Antiviral Effect of the Chemical Compounds Targeting DED/EDh Motifs of the Viral Proteins on Lymphocytic Choriomeningitis Virus and SARS-CoV-2.

Autor: Ngwe Tun MM; Department of Virology, Institute of Tropical Medicine and Leading Program, Graduate School of Biomedical Science, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan., Morita K; Department of Virology, Institute of Tropical Medicine and Leading Program, Graduate School of Biomedical Science, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan., Ishikawa T; Department of Chemistry, Biotechnology and Chemical Engineering, Graduate School of Science and Engineering, Kagoshima University, 1-21-40 Korimoto, Kagoshima 890-0065, Japan., Urata S; National Research Center for the Control and Prevention of Infectious Diseases (CCPID), Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
Jazyk: angličtina
Zdroj: Viruses [Viruses] 2021 Jun 24; Vol. 13 (7). Date of Electronic Publication: 2021 Jun 24.
DOI: 10.3390/v13071220
Abstrakt: 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.
Databáze: MEDLINE
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