Antiviral activity of pyrazole derivatives bearing a hydroxyquinoline scaffold against SARS-CoV-2, HCoV-229E, MERS-CoV, and IBV propagation

Abstract

The ongoing global threat posed by coronaviruses necessitates the urgent development of effective antiviral agents. In this study, we investigated the potential of hydroxyquinoline-pyrazole candidates as antiviral agents against a range of coronaviruses, including SARS-CoV-2, MERS-CoV, and HCoV-229E. Molecular docking studies were conducted to assess the binding affinity of the synthesized compounds to key viral proteins. The compounds were prepared <i>via</i> condensation reactions of a pyrazolylhydrazide derivative with 2-chloro-3-formylquinoline, yielding hydrazone and pyrrolone derivatives. The cytotoxicity of compounds was evaluated using Vero E6 cells, and their antiviral activity was assessed <i>via</i> plaque reduction assays and viral inhibition assays using hydroxychloroquine as a positive control antiviral drug. The results revealed promising antiviral activity of the synthesized compounds against all tested coronaviruses, with selectivity indices indicating their potential as selective antiviral agents. Notably, the compounds exhibited potent inhibition of SARS-CoV-2 at lower concentrations, highlighting their promise as therapeutic candidates against this highly pathogenic virus. Likewise, the modeling pharmacokinetics approach showed its appropriate drug-likeness and bioavailability assets. These findings underscore the importance of hydroxyquinoline-pyrazole derivatives as potential antiviral agents against diverse coronaviruses, providing valuable insights for further therapeutic development.