Combined molecular docking and dynamics simulations studies of natural compounds as potent inhibitors against SARS-CoV-2 main protease

Abstract

Main protease (Mpro) of SARS-CoV-2 is a key CoV enzyme that plays a pivotal role in mediating viral replication and transcription, making it an attractive drug target for SARS-CoV-2 the new strain of coronavirus. In this study, we evaluated biologically active compounds present in medicinal plants as potential SARS-CoV-2 Mpro inhibitors, using a molecular docking study with Autodock Vina software. Top seven compounds Afzelin, Phloroglucinol, Myricetin-3-O- rutinosid Tricin 7-neohesperidoside, Silybin, Kaempferol and Silychristin among 50 molecules of natural Origin (Algerian Medicinal plants) were selected which had better and significantly low binding energy as compared to the reference molecule with binding affinities of −9.3, −9.3, −9, −8.9, −8.5, 8.3 and −8.3 kcal mol⁻¹ respectively. Then, we analyzed the ADME properties of the best 7 ligands using the Web server SwissADME. Two of small molecules have been shown to be the ideal candidates for further drug development. Finally, the stability of the both compounds complexed with Mpro was validated through molecular dynamics (MD) simulation, they displayed stable trajectory (RMSD, RMSF) and molecular properties with consistent interaction profile in molecular dynamics simulations, moreover, Silybin could form more stable complex with Mpro than Silychristin.

Communicated by Ramaswamy H. Sarma

Keywords:

• COVID-19
• Medicinal plants
• Molecular docking
• ADME properties
• Molecular dynamics

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

We would like to express our gratefullness to the “Agence Universitaire de la Francophone (AUF)” for funding research project (Reference: AUF- 463/2020. Title: Repositionnement des médicaments et le dépistage in silico de certains composés issus des ressources naturelles pour le SAR-COV-2 via les méthodes de modélisation moléculaire).