Structure-based drug design, molecular dynamics simulation, ADMET, and quantum chemical studies of some thiazolinones targeting influenza neuraminidase

Abstract

The genetic mutability of the influenza virus leads to the existence of drug-resistant strains which is dangerous, particularly with the lingering coronavirus disease (COVID-19). This necessitated the need for the search and discovery of more potential anti-influenza agents to avert future outbreaks. In furtherance of our previous in-silico studies on 5-benzyl-4-thiazolinones as anti-influenza neuraminidase (NA) inhibitors, molecule 11 was selected as the template scaffold for the structure-based drug design due to its good binding, pharmacokinetic profiling, and better NA inhibitory activity. As such, eighteen (18) new molecules (11a-r) were designed with better MolDock scores as compared with the template scaffold and the zanamivir reference drug. However, the dynamic stability of molecule 11a in the binding cavity of the NA target (3TI5) showed water-mediated hydrogen and hydrophobic bondings with the active residues such as Arg118, Ile149, Arg152, Ile222, Trp403, and Ile427 after the MD simulation for 100 ns. The drug-likeness and ADMET assessment of all designed molecules predicted non-violation of the stipulated thresholds of Lipinski’s rule and good pharmacokinetic properties respectively. In addition, the quantum chemical calculations also suggested the significant chemical reactivity of molecules with their smaller band energy gap, high electrophilicity, high softness, and low hardness. The results obtained in this study proposed a reliable in-silico viewpoint for anti-influenza drug discovery and development.

Communicated by Ramaswamy H. Sarma

Keywords:

• influenza
• MolDock score
• neuraminidase
• binding cavity
• residual interaction

Authors’ contributions

MA, AU, GAS, PAM, and MTI did the conception and design of the work. MA, MTI, HP, and IA did the acquisition and analysis of the data. MA and MTI interpreted the data. MA, HP, and IA drafted the manuscript. MA and MTI substantively revised the manuscript. All authors read and approved the final manuscript

Acknowledgments

The authors remain grateful to the G.F.S. Harrison Quantum Chemistry Research Group in the Department of Chemistry, Ahmadu Bello University, Zaria

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.