HIGH-THROUGHPUT SCREENING AND DYNAMIC STUDIES OF SELECTED COMPOUNDS AGAINST SARS-COV-2

Ratul Bhowmik,Ratna Roy,Riya Biswas,Sameer Sharma,Ranajit Nath

doi:10.22159/ijap.2022v14i1.43105

Abstract

Objective: This study was aimed to analyze the inhibitory effect of the drugs used in nanocarrier as well as nanoparticles formulation based drug delivery system selected from PubChem database literature against 3CLpro (3C-like protease) receptor of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) by implementing several in silico analysis techniques. Methods: This paper detailed a molecular docking-based virtual screening of 5240 compounds previously utilized in nanoparticle and nanocarrier drug delivery systems utilizing AutoDock Vina software on 3CL protease to discover potential inhibitors using a molecular docking technique. Results: According to the results of the screening, the top two compounds, PubChem Id 58823276 and PubChem Id 60838 exhibited a high affinity for the 3CL protease binding region. Their binding affinities were-9.6 and-8.5 kJ/mol, indicating that they were tightly bound to the target receptor, respectively. These results outperformed those obtained using the co-crystallized native ligand, which exhibited a binding affinity of-7.4 kJ/mol. PubChem Id 60838, the main hit compound in terms of both binding affinity and ADMET analysis, displayed substantial deformability after MD simulation. As a result of the VS and molecular docking techniques, novel 3CL protease inhibitors from the PubChem database were discovered using the Lipinski rule of five and functional molecular contacts with the target protein, as evidenced by the findings of this work. Conclusion: The findings suggest that the compounds discovered may represent attractive opportunities for the development of COVID-19 3CLpro inhibitors and that they need further evaluation and investigation.

Highlights

According to scientific discovery, COVID-19 may have three phases
A total of 5240 compounds were identified from an intense literature survey from the PubChem database which had been previously used as drugs in nanoparticle or nanocarrier drug delivery systems. These compounds were docked with the targeted receptor SARS-CoV-2 3CL protease
The native ligand of the retrieved receptor SARS-CoV-2 3CL protease was separately docked with the receptor to compare the binding affinity of the native ligand with the hit compounds

Summary

Introduction

COVID-19 may have three phases. Certain medications are probably more effective when used independently of the other phases. The world is currently experiencing a COVID-19 pandemic (caused by SARS-CoV-2) for which no effective antiviral drugs or immunizations have been developed. The virus contains four non-structural proteins: papain-like (PLpro) and 3-chymotrypsin-like (3CLpro) proteases, RNA polymerase, and helicase. Both proteases (PLpro and 3CLpro) are involved in the transcription and replication stages of the virus. The primary protease 3CLpro of COVID19 exhibits 96 percent structural similarities to the SARS-CoV protease, according to a study. The 3CLpro enzyme is the major enzyme required for the proteolysis process It destroys the viral polyprotein, separating it into functional components that can be used independently. Because of its crucial function in the virus life cycle, 3CLpro is an excellent target for the development of effective antiviral medications against a range of Coronaviruses [3]

Methods

Results

Discussion

Conclusion