Tags

Type your tag names separated by a space and hit enter

Drug repurposing studies targeting SARS-CoV-2: an ensemble docking approach on drug target 3C-like protease (3CLpro).
J Biomol Struct Dyn. 2020 Jul 17 [Online ahead of print]JB

Abstract

The COVID-19 pandemic has been responsible for several deaths worldwide. The causative agent behind this disease is the Severe Acute Respiratory Syndrome - novel Coronavirus 2 (SARS-CoV-2). SARS-CoV-2 belongs to the category of RNA viruses. The main protease, responsible for the cleavage of the viral polyprotein is considered as one of the hot targets for treating COVID-19. Earlier reports suggest the use of HIV anti-viral drugs for targeting the main protease of SARS-CoV, which caused SARS in the year 2002-2003. Hence, drug repurposing approach may prove to be useful in targeting the main protease of SARS-CoV-2. The high-resolution crystal structure of the main protease of SARS-CoV-2 (PDB ID: 6LU7) was used as the target. The Food and Drug Administration approved and SWEETLEAD database of drug molecules were screened. The apo form of the main protease was simulated for a cumulative of 150 ns and 10 μs open-source simulation data was used, to obtain conformations for ensemble docking. The representative structures for docking were selected using RMSD-based clustering and Markov State Modeling analysis. This ensemble docking approach for the main protease helped in exploring the conformational variation in the drug-binding site of the main protease leading to the efficient binding of more relevant drug molecules. The drugs obtained as top hits from the ensemble docking possessed anti-bacterial and anti-viral properties. This in silico ensemble docking approach would support the identification of potential candidates for repurposing against COVID-19. Communicated by Ramaswamy H. Sarma.

Authors+Show Affiliations

High-Performance Computing-Medical and Bioinformatics Applications Group, Centre for Development of Advanced Computing (C-DAC), Panchavati, Pashan, Pune, India.High-Performance Computing-Medical and Bioinformatics Applications Group, Centre for Development of Advanced Computing (C-DAC), Panchavati, Pashan, Pune, India.High-Performance Computing-Medical and Bioinformatics Applications Group, Centre for Development of Advanced Computing (C-DAC), Panchavati, Pashan, Pune, India.High-Performance Computing-Medical and Bioinformatics Applications Group, Centre for Development of Advanced Computing (C-DAC), Panchavati, Pashan, Pune, India.High-Performance Computing-Medical and Bioinformatics Applications Group, Centre for Development of Advanced Computing (C-DAC), Panchavati, Pashan, Pune, India.High-Performance Computing-Medical and Bioinformatics Applications Group, Centre for Development of Advanced Computing (C-DAC), Panchavati, Pashan, Pune, India.High-Performance Computing-Medical and Bioinformatics Applications Group, Centre for Development of Advanced Computing (C-DAC), Panchavati, Pashan, Pune, India.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32679006

Citation

Koulgi, Shruti, et al. "Drug Repurposing Studies Targeting SARS-CoV-2: an Ensemble Docking Approach On Drug Target 3C-like Protease (3CLpro)." Journal of Biomolecular Structure & Dynamics, 2020, pp. 1-21.
Koulgi S, Jani V, Uppuladinne M, et al. Drug repurposing studies targeting SARS-CoV-2: an ensemble docking approach on drug target 3C-like protease (3CLpro). J Biomol Struct Dyn. 2020.
Koulgi, S., Jani, V., Uppuladinne, M., Sonavane, U., Nath, A. K., Darbari, H., & Joshi, R. (2020). Drug repurposing studies targeting SARS-CoV-2: an ensemble docking approach on drug target 3C-like protease (3CLpro). Journal of Biomolecular Structure & Dynamics, 1-21. https://doi.org/10.1080/07391102.2020.1792344
Koulgi S, et al. Drug Repurposing Studies Targeting SARS-CoV-2: an Ensemble Docking Approach On Drug Target 3C-like Protease (3CLpro). J Biomol Struct Dyn. 2020 Jul 17;1-21. PubMed PMID: 32679006.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Drug repurposing studies targeting SARS-CoV-2: an ensemble docking approach on drug target 3C-like protease (3CLpro). AU - Koulgi,Shruti, AU - Jani,Vinod, AU - Uppuladinne,Mallikarjunachari, AU - Sonavane,Uddhavesh, AU - Nath,Asheet Kumar, AU - Darbari,Hemant, AU - Joshi,Rajendra, Y1 - 2020/07/17/ PY - 2020/7/18/entrez PY - 2020/7/18/pubmed PY - 2020/7/18/medline KW - 3CLpro KW - COVID-19 KW - SARS-CoV-2 KW - cryptic pockets KW - main protease KW - repurposing SP - 1 EP - 21 JF - Journal of biomolecular structure & dynamics JO - J. Biomol. Struct. Dyn. N2 - The COVID-19 pandemic has been responsible for several deaths worldwide. The causative agent behind this disease is the Severe Acute Respiratory Syndrome - novel Coronavirus 2 (SARS-CoV-2). SARS-CoV-2 belongs to the category of RNA viruses. The main protease, responsible for the cleavage of the viral polyprotein is considered as one of the hot targets for treating COVID-19. Earlier reports suggest the use of HIV anti-viral drugs for targeting the main protease of SARS-CoV, which caused SARS in the year 2002-2003. Hence, drug repurposing approach may prove to be useful in targeting the main protease of SARS-CoV-2. The high-resolution crystal structure of the main protease of SARS-CoV-2 (PDB ID: 6LU7) was used as the target. The Food and Drug Administration approved and SWEETLEAD database of drug molecules were screened. The apo form of the main protease was simulated for a cumulative of 150 ns and 10 μs open-source simulation data was used, to obtain conformations for ensemble docking. The representative structures for docking were selected using RMSD-based clustering and Markov State Modeling analysis. This ensemble docking approach for the main protease helped in exploring the conformational variation in the drug-binding site of the main protease leading to the efficient binding of more relevant drug molecules. The drugs obtained as top hits from the ensemble docking possessed anti-bacterial and anti-viral properties. This in silico ensemble docking approach would support the identification of potential candidates for repurposing against COVID-19. Communicated by Ramaswamy H. Sarma. SN - 1538-0254 UR - https://www.unboundmedicine.com/medline/citation/32679006/Drug_repurposing_studies_targeting_SARS_CoV_2:_an_ensemble_docking_approach_on_drug_target_3C_like_protease__3CLpro__ L2 - http://www.tandfonline.com/doi/full/10.1080/07391102.2020.1792344 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.