Abstract
For the last few years, the world has been going through a difficult time, and the reason behind this is severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), one of the significant members of the Coronaviridae family. The major research groups have shifted their focus towards finding a vaccine and drugs against SARS-CoV-2 to reduce the infection rate and save the life of human beings. Even the WHO has permitted using certain vaccines for an emergency attempt to cut the infection curve down. However, the virus has a great sense of mutation, and the vaccine’s effectiveness remains questionable. No natural medicine is available at the community level to cure the patients for now. In this study, we have screened the vast library of experimental drugs of Drug Bank with Schrodinger’s maestro by using three algorithms: high-throughput virtual screening (HTVS), standard precision, and extra precise docking followed by Molecular Mechanics/Generalized Born Surface Area (MMGBSA). We have identified 3-(7-diaminomethyl-naphthalen-2-YL)-propionic acid ethyl ester and Thymidine-5′-thiophosphate as potent inhibitors against the SARS-CoV-2, and both drugs performed impeccably and showed stability during the 100 ns molecular dynamics simulation. Both of the drugs are among the category of small molecules and have an acceptable range of ADME properties. They can be used after their validation in in-vitro and in-vivo conditions.
Keywords: RNA-dependent RNA polymerase; SARS-CoV-2; molecular docking; molecular dynamics simulation; replication-transcription complex.
【저자키워드】 SARS-CoV-2, molecular docking, Molecular dynamics simulation, RNA-dependent RNA polymerase, replication-transcription complex., 【초록키워드】 Vaccine, Mutation, Experimental drugs, Infection, molecular docking, Virtual screening, drug, docking, molecular dynamics, virus, ADME, Molecular dynamics simulation, RNA, Severe acute respiratory syndrome, stability, Research, Effectiveness, Community, RNA-dependent RNA polymerase, Small molecules, small molecule, infection rate, surface, molecular, RNA polymerase, group, inhibitor, In-vitro, followed by, surface area, replication-transcription complex, Precision, thymidine, reason, Coronaviridae family, Drug Bank, thiophosphate, performed, the patient, screened, can be used, reduce, the WHO, the vaccine, conditions, the Coronaviridae, Area, Bank, experimental drug, the SARS-CoV-2, 【제목키워드】 Dynamics, drug, Screening, Simulation, Compound, Bank,