Strategic analyses to identify key structural features of antiviral/antimalarial compounds for their binding interactions with 3CLpro, PLpro and RdRp of SARS-CoV-2: in silico molecular docking and dynamic simulation studies.
| Title: | Strategic analyses to identify key structural features of antiviral/antimalarial compounds for their binding interactions with 3CLpro, PLpro and RdRp of SARS-CoV-2: in silico molecular docking and dynamic simulation studies. |
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| Authors: | Dhote AM; Department of Pharmaceutical Chemistry, R.C. Patel Institute of Pharmaceutical Education and Research, Maharashtra, India.; Patil VR; Department of Pharmaceutical Chemistry, R.C. Patel Institute of Pharmaceutical Education and Research, Maharashtra, India.; Lokwani DK; Department of Pharmaceutical Chemistry, R.C. Patel Institute of Pharmaceutical Education and Research, Maharashtra, India.; Amnerkar ND; Department of Pharmaceutical Chemistry, Adv. V. R. Manohar Institute of Diploma in Pharmacy, Nagpur, India.; Ugale VG; Department of Pharmaceutical Chemistry, R.C. Patel Institute of Pharmaceutical Education and Research, Maharashtra, India.; Charbe NB; Department of Pharmaceutical Sciences, Rangel College of Pharmacy, Texas A&M University, Kingsville, TX, USA.; Bhongade BA; Department of Pharmaceutical Chemistry, RAK College of Pharmaceutical Sciences, RAK Medical & Health Sciences University, Ras Al Khaimah, UAE.; Khadse SC; Department of Pharmaceutical Chemistry, R.C. Patel Institute of Pharmaceutical Education and Research, Maharashtra, India. |
| Source: | Journal of biomolecular structure & dynamics [J Biomol Struct Dyn] 2022; Vol. 40 (22), pp. 11914-11931. Date of Electronic Publication: 2021 Aug 25. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Taylor & Francis Country of Publication: England NLM ID: 8404176 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-0254 (Electronic) Linking ISSN: 07391102 NLM ISO Abbreviation: J Biomol Struct Dyn Subsets: MEDLINE |
| Imprint Name(s): | Publication: June 2012- : Oxon, UK : Taylor & Francis; Original Publication: Guilderland, NY : Adenine Press, [c1983- |
| MeSH Terms: | Antimalarials*/pharmacology ; COVID-19*; Antiviral Agents/chemistry ; Saquinavir/pharmacology ; RNA-Dependent RNA Polymerase/chemistry ; Adenine/analogs & derivatives ; Humans ; SARS-CoV-2 ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Organophosphonates |
| Abstract: | Severe acute respiratory syndrome coronavirus (SARS-CoV-2), a novel member of the betacoronavirus family is a single-stranded RNA virus that has spread worldwide prompting the World Health Organization to declare a global pandemic. This creates an alarming situation and generates an urgent need to develop innovative therapeutic agents. In this context, an in silico molecular docking and molecular dynamics (MD) simulation study on the existing 58 antiviral and antimalarial compounds was performed on 3CLpro, PLpro and RdRp SARS-CoV-2 proteins. The antiviral compounds are best fitted in the binding pockets and interact more profoundly with the amino acid residues compared to antimalarial compounds. An HIV protease inhibitor, saquinavir showed a good dock score and binding free energy with varied binding interactions against 3CLpro and PLpro. While, adefovir, a nucleotide HBV DNA polymerase inhibitor exhibited good dock score and binding interactions against RdRp. Although, the antimalarial compounds showed relatively less dock score but were found to be crucial in displaying essential binding interactions with these proteins. The MD simulation runs for 100 ns on 3CLpro-saquinavir, PLpro-saquinavir and RdRp-adefovir complexes using Desmond revealed fairly stable nature of interactions. This study helped in understanding the key interactions of the vital functionalities that provide a concrete base to develop lead molecules effective against SARS-CoV-2. |
| Contributed Indexing: | Keywords: 3CLpro; PLpro; RdRp; SARS-CoV-2; docking; dynamics |
| Substance Nomenclature: | 0 (Antiviral Agents); 0 (Antimalarials); L3JE09KZ2F (Saquinavir); EC 2.7.7.48 (RNA-Dependent RNA Polymerase); 6GQP90I798 (adefovir); JAC85A2161 (Adenine); 0 (Organophosphonates) |
| Entry Date(s): | Date Created: 20210825 Date Completed: 20221223 Latest Revision: 20260127 |
| Update Code: | 20260130 |
| DOI: | 10.1080/07391102.2021.1965912 |
| PMID: | 34431452 |
| Database: | MEDLINE |
Journal Article