Article
Open Access
Volume 2 · Issue 4 · 2022
pp. 181–191
Molecular Docking and Simulation Study of Calcium Channel Blockers on SARS-CoV-2 ORF3a Protein
Hanuman Singh Dagur1, Saurabh Singh Dhakar2
1
Department of Biotechnology, Indian Institute of Technology Hyderabad, Telangana, India
2
Department of Bioscience and Bioengineering, Indian Institute of Technology Bombay, Maharashtra, India
Abstract
Objectives: The covid-19, a viral disease caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has turned into pandemic. The genome of SARS-CoV-2 encodes 14 open reading frames, produced from transcription of sub genomic RNAs. It encodes for sixteen non-structural proteins, four structural proteins and eight accessory proteins. The accessory protein, ORF3a is a viroporin with ion channel activity and has been shown to be crucial for the viral release and pathogenicity of SARS-CoV-2.
Methods: We used a combination of virtual database screening, molecular docking and all-atom molecular dynamics simulation analysis to screen calcium channel blocker drugs as potential inhibitors of ion channel formed by SARS-CoV-2 ORF3a protein.
Results: Interaction and molecular dynamics simulation analysis showed that hydrogen bond and hydrophobic interaction were the major driving forces for binding of the drugs, with Niguldipine being the most promising inhibitor. Niguldipine is bound at the lumen of the channel formed by ORF3a protein, indicating as a potential inhibitor of functionality of the viroporin ORF3a protein. In MD simulations, niguldipine demonstrated stable conformational dynamics with SARS-CoV-2 ORF3a protein.
Conclusion: Molecular and MD simulation study highlights the possibility of exploring calcium channel blocker drug, niguldipine as a potential SARS-CoV-2 ORF3a protein ion channel blocker to inhibit the viral infection.
Methods: We used a combination of virtual database screening, molecular docking and all-atom molecular dynamics simulation analysis to screen calcium channel blocker drugs as potential inhibitors of ion channel formed by SARS-CoV-2 ORF3a protein.
Results: Interaction and molecular dynamics simulation analysis showed that hydrogen bond and hydrophobic interaction were the major driving forces for binding of the drugs, with Niguldipine being the most promising inhibitor. Niguldipine is bound at the lumen of the channel formed by ORF3a protein, indicating as a potential inhibitor of functionality of the viroporin ORF3a protein. In MD simulations, niguldipine demonstrated stable conformational dynamics with SARS-CoV-2 ORF3a protein.
Conclusion: Molecular and MD simulation study highlights the possibility of exploring calcium channel blocker drug, niguldipine as a potential SARS-CoV-2 ORF3a protein ion channel blocker to inhibit the viral infection.
Keywords: SARS-CoV2, ORF3a Protein, Molecular Docking, MD Simulation
