In-Silico Screening and Molecular Dynamics Simulation of Drug Bank Experimental Compounds against SARS-CoV-2

Norah A Alturki; Mutaib M Mashraqi; Ahmad Alzamami; Youssef S Alghamdi; Afaf A Alharthi; Saeed A Asiri; Shaban Ahmad; Saleh Alshamrani

doi:10.3390/molecules27144391

In-Silico Screening and Molecular Dynamics Simulation of Drug Bank Experimental Compounds against SARS-CoV-2

Molecules. 2022 Jul 8;27(14):4391. doi: 10.3390/molecules27144391.

Authors

Norah A Alturki¹, Mutaib M Mashraqi², Ahmad Alzamami³, Youssef S Alghamdi⁴, Afaf A Alharthi⁵, Saeed A Asiri², Shaban Ahmad⁶, Saleh Alshamrani²

Affiliations

¹ Clinical Laboratory Science Department, College of Applied Medical Science, King Saud University, Riyadh 11433, Saudi Arabia.
² Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran 61441, Saudi Arabia.
³ Clinical Laboratory Science Department, College of Applied Medical Science, Shaqra University, Al Quwayiyah 11961, Saudi Arabia.
⁴ Department of Biology, Turabah University College, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
⁵ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
⁶ Agriculture Knowledge Management Unit, ICAR-Indian Agricultural Research Institute, New Dehli 110012, India.

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.

MeSH terms

Antiviral Agents / pharmacology
COVID-19 Drug Treatment*
Humans
Molecular Docking Simulation
Molecular Dynamics Simulation
Protease Inhibitors / pharmacology
SARS-CoV-2*

Substances

Antiviral Agents
Protease Inhibitors

Grants and funding

TURSP-2020/258/Taif University