article · RSC Advances
Coronaviruses continue to pose significant public health challenges, driving the need for new therapeutic options. Chemical compounds combining pyrazole and hydroxyquinoline scaffolds were synthesised and evaluated for their ability to combat several coronaviruses, including SARS-CoV-2, MERS-CoV, and HCoV-229E. Computational docking simulations were utilised to evaluate how effectively the molecules bind to critical viral proteins, while pharmacokinetic modelling assessed their drug-likeness and potential bioavailability. In laboratory testing on Vero E6 cells, cytotoxicity assays established compound safety margins, and plaque reduction assays measured antiviral efficacy against hydroxychloroquine as a control. The synthesised derivatives demonstrated broad antiviral activity across the tested coronaviruses, displaying favourable selectivity indices. In particular, the molecules strongly inhibited SARS-CoV-2 replication at lower concentrations, indicating their potential as candidates for future drug development against coronavirus infections.
Emerging and circulating coronaviruses can cause severe respiratory illnesses and widespread disruption. Developing novel broad-spectrum antivirals targeting multiple viral strains helps prepare healthcare systems for current outbreaks and future variants. Demonstrating that these dual-scaffold molecules have both high viral inhibition and suitable drug-like properties provides a valuable foundation for designing safer and more effective coronavirus treatments.
This research could aid pharmaceutical companies and drug development programmes seeking lead compounds for broad-spectrum antiviral therapies. The work remains at an early discovery stage, having demonstrated in vitro cellular efficacy, low cellular toxicity, and computational pharmacokinetic feasibility. Significant further testing, including in vivo animal models, full preclinical safety trials, and formulation development, will be required before any commercial clinical development can begin.
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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.
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DOI: 10.1039/d4ra04728a
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