Identification of Novel Drug Candidates for the Inhibition of Catalytic Cleavage Activity of Coronavirus 3CL-like Protease Enzyme.
Curr Pharm Biotechnol
; 23(7): 959-969, 2022.
Article
in English
| MEDLINE | ID: covidwho-1259293
ABSTRACT
BACKGROUND:
There has been tremendous pressure on healthcare facilities globally due to the recent emergence of novel coronavirus infection known as COVID-19 and its rapid spread across the continents. The lack of effective therapeutics for the management of the pandemic calls for the discovery of new drugs and vaccines.OBJECTIVE:
In the present study, a chemical library was screened for molecules against three coronavirus 3CL-like protease enzymes (SARS-CoV-2 3CLpro, SARS-CoV 3CLpro and MERS-CoV 3CLpro), which are a key player in the viral replication cycle.METHODS:
Extensive computational methods such as virtual screening and molecular docking were employed in this study.RESULTS:
Two lead molecules, ZINC08825480 (4-bromo-N'-{(E)-[1-phenyl-3-(pyridin-3-yl)-1H-pyrazol- 4-yl]methylidene}benzene-1-sulfonohydrazide) and ZINC72009942 (N-[[2-[[(3S)-3-methyl-1-piperidyl] methyl]phenyl]methyl]-6-oxo-1-(p-tolyl)-4,5-dihydro-1,2,4-triazine-3-carboxamide), were identified with better affinity with the three target enzymes as compared to the approved antiviral drugs. Both the lead molecules possessed favorable drug-like properties, fit well into the active site pocket close to His- Cys dyad and showed a good number of hydrogen bonds with the backbone as well as side chains of key amino acid residues.CONCLUSION:
Thus, the present study offers two novel chemical entities against coronavirus infections which can be validated through various biological assays.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Middle East Respiratory Syndrome Coronavirus
/
COVID-19 Drug Treatment
Type of study:
Prognostic study
Topics:
Vaccines
Limits:
Humans
Language:
English
Journal:
Curr Pharm Biotechnol
Journal subject:
Biotechnology
/
Pharmacology
Year:
2022
Document Type:
Article
Affiliation country:
1389201022666210604150041
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