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Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents.
Commun Biol. 2021 01 20; 4(1):93.CB

Abstract

Emerging outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a major threat to public health. The morbidity is increasing due to lack of SARS-CoV-2 specific drugs. Herein, we have identified potential drugs that target the 3-chymotrypsin like protease (3CLpro), the main protease that is pivotal for the replication of SARS-CoV-2. Computational molecular modeling was used to screen 3987 FDA approved drugs, and 47 drugs were selected to study their inhibitory effects on SARS-CoV-2 specific 3CLpro enzyme in vitro. Our results indicate that boceprevir, ombitasvir, paritaprevir, tipranavir, ivermectin, and micafungin exhibited inhibitory effect towards 3CLpro enzymatic activity. The 100 ns molecular dynamics simulation studies showed that ivermectin may require homodimeric form of 3CLpro enzyme for its inhibitory activity. In summary, these molecules could be useful to develop highly specific therapeutically viable drugs to inhibit the SARS-CoV-2 replication either alone or in combination with drugs specific for other SARS-CoV-2 viral targets.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, School of Pharmacy, Philadelphia College of Osteopathic Medicine - Georgia Campus, Suwanee, GA, USA.Department of Pharmaceutical Sciences, School of Pharmacy, Philadelphia College of Osteopathic Medicine - Georgia Campus, Suwanee, GA, USA.Department of Pharmaceutical Sciences, School of Pharmacy, Philadelphia College of Osteopathic Medicine - Georgia Campus, Suwanee, GA, USA.Department of Pharmaceutical Sciences, School of Pharmacy, Philadelphia College of Osteopathic Medicine - Georgia Campus, Suwanee, GA, USA.Department of Pharmaceutical Sciences, School of Pharmacy, Philadelphia College of Osteopathic Medicine - Georgia Campus, Suwanee, GA, USA.Chemical Computing Group, 910-1010 Sherbrooke W, Montreal, QC, H3A 2R7, Canada.Chemical Computing Group, 910-1010 Sherbrooke W, Montreal, QC, H3A 2R7, Canada.Department of Pharmaceutical Sciences, School of Pharmacy, Philadelphia College of Osteopathic Medicine - Georgia Campus, Suwanee, GA, USA.Department of Pharmaceutical Sciences, School of Pharmacy, Philadelphia College of Osteopathic Medicine - Georgia Campus, Suwanee, GA, USA. rangaiahsh@pcom.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33473151

Citation

Mody, Vicky, et al. "Identification of 3-chymotrypsin Like Protease (3CLPro) Inhibitors as Potential anti-SARS-CoV-2 Agents." Communications Biology, vol. 4, no. 1, 2021, p. 93.
Mody V, Ho J, Wills S, et al. Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents. Commun Biol. 2021;4(1):93.
Mody, V., Ho, J., Wills, S., Mawri, A., Lawson, L., Ebert, M. C. C. J. C., Fortin, G. M., Rayalam, S., & Taval, S. (2021). Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents. Communications Biology, 4(1), 93. https://doi.org/10.1038/s42003-020-01577-x
Mody V, et al. Identification of 3-chymotrypsin Like Protease (3CLPro) Inhibitors as Potential anti-SARS-CoV-2 Agents. Commun Biol. 2021 01 20;4(1):93. PubMed PMID: 33473151.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents. AU - Mody,Vicky, AU - Ho,Joanna, AU - Wills,Savannah, AU - Mawri,Ahmed, AU - Lawson,Latasha, AU - Ebert,Maximilian C C J C, AU - Fortin,Guillaume M, AU - Rayalam,Srujana, AU - Taval,Shashidharamurthy, Y1 - 2021/01/20/ PY - 2020/08/07/received PY - 2020/12/08/accepted PY - 2021/1/21/entrez PY - 2021/1/22/pubmed PY - 2021/1/28/medline SP - 93 EP - 93 JF - Communications biology JO - Commun Biol VL - 4 IS - 1 N2 - Emerging outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a major threat to public health. The morbidity is increasing due to lack of SARS-CoV-2 specific drugs. Herein, we have identified potential drugs that target the 3-chymotrypsin like protease (3CLpro), the main protease that is pivotal for the replication of SARS-CoV-2. Computational molecular modeling was used to screen 3987 FDA approved drugs, and 47 drugs were selected to study their inhibitory effects on SARS-CoV-2 specific 3CLpro enzyme in vitro. Our results indicate that boceprevir, ombitasvir, paritaprevir, tipranavir, ivermectin, and micafungin exhibited inhibitory effect towards 3CLpro enzymatic activity. The 100 ns molecular dynamics simulation studies showed that ivermectin may require homodimeric form of 3CLpro enzyme for its inhibitory activity. In summary, these molecules could be useful to develop highly specific therapeutically viable drugs to inhibit the SARS-CoV-2 replication either alone or in combination with drugs specific for other SARS-CoV-2 viral targets. SN - 2399-3642 UR - https://www.unboundmedicine.com/medline/citation/33473151/Identification_of_3_chymotrypsin_like_protease__3CLPro__inhibitors_as_potential_anti_SARS_CoV_2_agents_ L2 - https://doi.org/10.1038/s42003-020-01577-x DB - PRIME DP - Unbound Medicine ER -