Identification of structural scaffold from interbioscreen (IBS) database to inhibit 3CLpro, PLpro, and RdRp of SARS-CoV-2 using molecular docking and dynamic simulation studies.
| Title: | Identification of structural scaffold from interbioscreen (IBS) database to inhibit 3CLpro, PLpro, and RdRp of SARS-CoV-2 using molecular docking and dynamic simulation studies. |
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| Authors: | Patil VR; Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Karvand Naka Shirpur, Dist. Dhule, Maharashtra, India.; Dhote AM; Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Karvand Naka Shirpur, Dist. Dhule, Maharashtra, India.; Patil R; Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Karvand Naka Shirpur, Dist. Dhule, Maharashtra, India.; Amnerkar ND; Department of Pharmaceutical Chemistry, Adv. V. R. Manohar Institute of Diploma in Pharmacy (Govt.-Aided), Nagpur, Nagpur, Maharashtra, India.; Lokwani DK; Department of Pharmaceutical Chemistry, Rajarshi Shahu College of Pharmacy, Buldana, Maharashtra, India.; Ugale VG; Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Karvand Naka Shirpur, Dist. Dhule, Maharashtra, India.; Charbe NB; Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, Florida, USA.; Firke SD; Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Karvand Naka Shirpur, Dist. Dhule, Maharashtra, India.; Chaudhari P; Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Karvand Naka Shirpur, Dist. Dhule, Maharashtra, India.; Shah SK; Department of Pharmaceutical Chemistry, Priyadarshini J. L. College of Pharmacy, Nagpur, Maharashtra, India.; Mehta CH; Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.; Nayak UY; Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.; Khadse SC; Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Karvand Naka Shirpur, Dist. Dhule, Maharashtra, India. |
| Source: | Journal of biomolecular structure & dynamics [J Biomol Struct Dyn] 2023; Vol. 41 (22), pp. 13168-13179. Date of Electronic Publication: 2023 Feb 09. |
| 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: | Peptide Hydrolases* ; COVID-19*; Protease Inhibitors/pharmacology ; Antiviral Agents/pharmacology ; Humans ; Papain ; Molecular Docking Simulation ; SARS-CoV-2 ; RNA-Dependent RNA Polymerase ; Molecular Dynamics Simulation |
| Abstract: | A novel coronavirus SARS-CoV-2 has caused a worldwide pandemic and remained a severe threat to the entire human population. Researchers worldwide are struggling to find an effective drug treatment to combat this deadly disease. Many FDA-approved drugs from varying inhibitory classes and plant-derived compounds are screened to combat this virus. Still, due to the lack of structural information and several mutations of this virus, initial drug discovery efforts have limited success. A high-resolution crystal structure of important proteins like the main protease (3CLpro) that are required for SARS-CoV-2 viral replication and polymerase (RdRp) and papain-like protease (PLpro) as a vital target in other coronaviruses still presents important targets for the drug discovery. With this knowledge, scaffold library of Interbioscreen (IBS) database was explored through molecular docking, MD simulation and postdynamic binding free energy studies. The 3D docking structures and simulation data for the IBS compounds was studied and articulated. The compounds were further evaluated for ADMET studies using QikProp and SwissADME tools. The results revealed that the natural compounds STOCK2N-00385, STOCK2N-00244, and STOCK2N-00331 interacted strongly with 3CLpro, PLpro, and RdRp, respectively, and ADMET data was also observed in the range of limits for almost all the compounds with few exceptions. Thus, it suggests that these compounds may be potential inhibitors of selected target proteins, or their structural scaffolds can be further optimized to obtain effective drug candidates for SARS-CoV-2. The findings of in-silico data need to be supported by in-vivo studies which could shed light on understanding the exact mode of inhibitory action.Communicated by Ramaswamy H. Sarma. |
| Contributed Indexing: | Keywords: ADMET; Docking; SARS-CoV-2; dynamics |
| Substance Nomenclature: | EC 3.4.- (Peptide Hydrolases); EC 3.4.22.2 (Papain); EC 2.7.7.48 (RNA-Dependent RNA Polymerase); 0 (Protease Inhibitors); 0 (Antiviral Agents) |
| Entry Date(s): | Date Created: 20230209 Date Completed: 20231127 Latest Revision: 20250410 |
| Update Code: | 20260130 |
| DOI: | 10.1080/07391102.2023.2175377 |
| PMID: | 36757134 |
| Database: | MEDLINE |
Journal Article