In Silico Exploration of Phytoconstituents From Phyllanthus emblica and Aegle marmelos as Potential Therapeutics Against SARS-CoV-2 RdRp
| Autor: | Kiran Bharat Lokhande, Manjusha Dake, K. Venkateswara Swamy, Khushboo Pandey, Shuchi Nagar |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Drug media_common.quotation_subject In silico Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses 030106 microbiology Phyllanthus emblica Pharmacology Biochemistry 03 medical and health sciences Medicine Molecular Biology media_common Original Research drug repurposing business.industry Applied Mathematics Minimum risk MD simulation molecular docking Computer Science Applications Computational Mathematics Drug repositioning 030104 developmental biology Aegle marmelos SARS-CoV-2 RdRp business |
| Zdroj: | Bioinformatics and Biology Insights |
| ISSN: | 1177-9322 |
| Popis: | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide has increased the importance of computational tools to design a drug or vaccine in reduced time with minimum risk. Earlier studies have emphasized the important role of RNA-dependent RNA polymerase (RdRp) in SARS-CoV-2 replication as a potential drug target. In our study, comprehensive computational approaches were applied to identify potential compounds targeting RdRp of SARS-CoV-2. To study the binding affinity and stability of the phytocompounds from Phyllanthus emblica and Aegel marmelos within the defined binding site of SARS-CoV-2 RdRp, they were subjected to molecular docking, 100ns molecular dynamics (MD) simulation followed by post-simulation analysis. Further, to assess the importance of features involved in the strong binding affinity, molecular field-based similarity analysis was performed. Based on comparative molecular docking and simulation studies of the selected phytocompounds with SARS-CoV-2 RdRp revealed that, EBDGp possess stronger binding affinity (-23.32 kcal/mol) and stability than other phytocompounds and reference compound, Remdesivir (-19.36 kcal/mol). Molecular field-based similarity profiling has supported our study in the validation of the importance of the presence of hydroxyl groups in EBDGp, involved in increasing its binding affinity towards SARS-CoV-2 RdRp. Molecular docking and dynamic simulation results confirmed that EBDGp has better inhibitory potential than Remdesivir and can be an effective novel drug for SARS-CoV-2 RdRp. Furthermore, binding free energy calculations confirmed the higher stability of the SARS-CoV-2 RdRp-EBDGp complex. These results suggest that the EBDGp compound may emerge as a promising drug against SARS-CoV-2 and hence requires further experimental validation. |
| Databáze: | OpenAIRE |
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