Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents.

Communications Biology
Vicky ModyShashidharamurthy Taval

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.

References

Jan 1, 1991·Journal of Virology·P B SethnaD A Brian
Jul 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·P B SethnaD A Brian
Jan 1, 1995·Advances in Experimental Medicine and Biology·S G Sawicki, D L Sawicki
Nov 6, 2007·Bioorganic & Medicinal Chemistry Letters·Alberto MalvezziAntonia do Amaral
Feb 8, 2011·Journal of Biomolecular Screening·Kylie M WagstaffDavid A Jans
Aug 28, 2012·Acta Pharmacologica Sinica·Si-Sheng Ou-YangHualiang Jiang
Jul 31, 2014·Expert Review of Anti-infective Therapy·Ivan GentileGuglielmo Borgia
May 7, 2015·Acta Crystallographica. Section D, Biological Crystallography·Danielle NeedleDavid S Waugh
Jul 21, 2015·Annals of the New York Academy of Sciences·David S Perlin
Sep 10, 2015·Biological Chemistry·Friederike K KosynaReinhard Depping
Nov 26, 2015·Current Pharmaceutical Design·Mohammad Hassan BaigInho Choi
Feb 3, 2016·Molecular Cancer Therapeutics·Pauline J van der WattVirna D Leaner
Feb 13, 2016·Nature Reviews. Drug Discovery·Alimuddin ZumlaKwok-Yung Yuen
Jan 25, 2020·The New England Journal of Medicine·Na ZhuUNKNOWN China Novel Coronavirus Investigating and Research Team
Feb 1, 2020·The New England Journal of Medicine·Michelle L HolshueUNKNOWN Washington State 2019-nCoV Case Investigation Team
Mar 5, 2020·Nature Reviews. Drug Discovery·Guangdi Li, Erik De Clercq
Mar 19, 2020·The New England Journal of Medicine·Bin CaoChen Wang
Apr 7, 2020·Antiviral Research·Leon CalyKylie M Wagstaff
Apr 8, 2020·Revista Panamericana De Salud Pública = Pan American Journal of Public Health·Sandro G Viveiros Rosa, Wilson C Santos
Apr 11, 2020·The New England Journal of Medicine·Jonathan GreinTimothy Flanigan
Jan 1, 1996·Perspectives in Drug Discovery and Design : PD3·Alexander E Gorbalenya, Eric J Snijder
Apr 17, 2020·Journal of Pharmaceutical Analysis·Muhammad Tahir Ul QamarLing-Ling Chen
Jun 14, 2020·The Journal of Antibiotics·Fatemeh Heidary, Reza Gharebaghi
Aug 6, 2020·The Journal of Chemical Physics·James C PhillipsEmad Tajkhorshid

❮ Previous
Next ❯

Citations

Mar 26, 2021·Journal of Endocrinological Investigation·G LiscoV Triggiani
Mar 31, 2021·Advances in Nutrition·Laurence DaoustAndré Marette
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Marco A Almaraz-GirónSandra L Castañón-Alonso
Jul 3, 2021·Antioxidants·Noemí Cárdenas-RodríguezBeatriz Hernández-Ochoa

❮ Previous
Next ❯

Methods Mentioned

BETA
enzymatic assay
X-ray
Fluorescence

Clinical Trials Mentioned

NCT04438850

Related Concepts

Related Feeds

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Anthelmintics (ASM)

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.