Abstract
Remdesivir was approved by the U.S.A. Food and Drug administration for emergency use to interfere with the replication of SARS CoV-2 virus (the agent that causes COVID-19) in adults and children hospitalized with severe disease. The crystal structure of the metabolite of remdesivir (Monophosphate of GS-441524) and NSP12-NSP8-NSP7 of SARS CoV-2 virus was recently reported. The crystal structures of ADP-Ribose or AMP and NSP3 of SARS CoV-2 virus were also released, recently. This study compared their binding sites and suggests the crystal structure of NSP3 of SARS CoV-2 virus as an alternative binding site of AMP or ADP-ribose to treat COVID-19. We virtually screened 682 FDA-approved compounds, and the top 10 compounds were selected by analysis of docking scores, (G-score, D-score, and Chemscore) and visual analysis using a structure-based docking approach of NSP3 of SARS CoV-2 virus. All immunization approaches are based on the SARS-CoV-2 virus spike protein. A recent study reported that the D614G mutation in the SARS-CoV-2 virus spike protein reduces S1 shedding and increases infectivity of SARS COV-2 virus. Therefore, if there is a severe change in the spike protein of a modified Coronavirus, all developed vaccines can lose their efficacy, necessitating the need for an alternative treatment method. The top 10 compounds (FDA-approved) in this study are selected based on NSP 3 binding site, and therefore are a potential viable treatment because they will show potential activity for all mutations in the SARS-CoV-2 virus spike protein.
Keywords: Non-structural protein 3 (NSP3) of SARS CoV-2 virus; Remdesivir; Virtual screening.
【저자키워드】 Remdesivir, Virtual screening, Non-structural protein 3 (NSP3) of SARS CoV-2 virus, 【초록키워드】 COVID-19, SARS CoV-2, Treatment, Efficacy, Vaccine, coronavirus, Nsp12, Mutation, Hospitalized, children, Remdesivir, SARS-CoV-2 virus, Virtual screening, drug, docking, virus, immunization, Spike protein, binding site, Replication, D614G mutation, GS-441524, non-structural protein, Nsp3, Nsp7, crystal structure, NSP8, metabolite, compounds, Emergency use, food, administration, Analysis, severe disease, crystal structures, protein 3, treatment method, agent, SARS CoV, Compound, docking scores, treat, viable treatment, ribose, monophosphate, ADP-ribose, approach, selected, reported, approved, screened, increase, the spike protein, interfere, cause, reduce, released, the SARS-CoV-2 virus, 【제목키워드】 COVID-19, Remdesivir, drug, Site, Potential,