Abstract

COMPUTATIONAL DESIGN AND MOLECULAR DOCKING OF PYRAZOLONE DERIVATIVES DERIVED FROM IMIDAZOLE HYDRAZIDE AGAINST SARS-COV-2 MAIN PROTEASE

Anjana V. S.*, Rose Mary Joseph, Ajna S. A., Anchu Raj, Chandu Nath

Abstract

The emergence of SARS-CoV-2 has highlighted the urgent need for effective antiviral agents, prompting the exploration of novel heterocyclic scaffolds through computational drug design approaches. In the present study, a series of fifty novel pyrazolone derivatives derived from imidazole hydrazide were designed and evaluated as potential inhibitors of the SARSCoV- 2 main protease (Mpro, PDB ID: 6LU7). The chemical structures of the compounds were drawn and optimized using ACD/ChemSketch software. The designed compounds were further assessed for drug-likeness through Lipinski’s rule of five using Molinspiration software, where all derivatives showed acceptable physicochemical properties. Biological activity prediction was carried out using PASS software, indicating favorable probabilities for antiviral activity. ADMET profiling further supported the suitability of the compounds for oral administration. Molecular docking studies were performed using AutoDock against SARS-CoV-2 Mpro, and several derivatives exhibited binding affinities comparable to or better than the standard drug ritonavir. Among them, compound A49 demonstrated the most promising docking score, suggesting strong interaction with the active site of the target enzyme. Overall, the study identifies pyrazolone–imidazole hydrazide derivatives as promising lead candidates for further synthesis and experimental validation as potential anti-COVID-19 agents.

Keywords: Pyrazolone derivatives, SARS-CoV-2, Main protease (Mpro), Molecular docking, In silico drug design, AutoDock.