Abstract
Background: There has been tremendous pressure on healthcare facilities globally due to therecent emergence of novel coronavirus infection known as COVID-19 and its rapid spread across thecontinents. The lack of effective therapeutics for the management of the pandemic calls for the discoveryof new drugs and vaccines.
Objective: In the present study, a chemical library was screened for molecules against three coronavirus3CL-like protease enzymes (SARS-CoV-2 3CLpro, SARS-CoV 3CLpro and MERS-CoV 3CLpro), whichare a key player in the viral replication cycle.
Methods: Extensive computational methods such as virtual screening and molecular docking were employedin 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 identifiedwith better affinity with the three target enzymes as compared to the approved antiviral drugs. Both thelead 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 keyamino acid residues.
Conclusion: Thus, the present study offers two novel chemical entities against coronavirus infectionswhich can be validated through various biological assays.