IJCEA 2024 Vol.15(2): 60-63
doi: 10.18178/ijcea.2024.15.2.825
Binding and Mechanism of Small Molecules Inhibitors of Influenza Virus H3N2 Hemagglutinin: Insights from Molecular Dynamics Simulation
Nadtanet Nunthaboot*, Thitiya Boonma, and Chananya Rajchakom
Multidisplinary Research Unit of Pure and Applied Chemistry and Supramolecular Chemistry Research Unit, Department of Chemistry and Center of Excellence for Innovation in Chemistry (PERCH‒CIC), Faculty of Science, Mahasarakham University, Maha Sarakham, 44150, Thailand
Email: nadtanet.n@msu.ac.th (N.N); thitiya.bm@gmail.com (T.B); 65010251004@o365.msu.ac.th (C.R.)
*Corresponding author
Manuscript received April 17, 2024; revised June 1, 2024; accepted July 7, 2024; published October 24, 2024
Abstract—Drugs targeting Neuraminidase (NA) and the M2 membrane protein are available in the market, however, their efficacies are significantly impeded by resistances arising from amino acid mutations, posing a major challenge and limiting drug efficiency. Consequently, there is a critical need to explore new drugs that target alternative protein targets. Hemagglutinin (HA), playing a pivotal role in the influenza viral replication cycle, has emerged as an attractive and promising target for the development of novel antiviral drugs. Tert-Butylhydroquinone (TBHQ) was reported to prevent the HA conformational change, thereby inhibiting the HA-mediated entry. Here, molecular dynamics simulations of HA of H3N2 and its inhibitors (TBHQ and derivatives) were performed to investigate their dynamical and structural behaviours. The results show that TBHQ can form more and stronger hydrogen bonds with residues E571 and E972, when compared to its analogues. These two residues possibly play a potential stabilizing effect on the HA structure. The results agree well with the predicted and experimental values of binding free energy. The detailed information can provide valuable insights into the structural dynamics of the HA-inhibitor complexes and offer potential avenues for the development of novel antiviral agents targeting influenza virus replication.
Keywords—Hemagglutinin, H3N2 Influenza virus, TBHQ, MD simulation, binding free energy, fusion inhibitor
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Cite: Nadtanet Nunthaboot, Thitiya Boonma, and Chananya Rajchakom, "Binding and Mechanism of Small Molecules Inhibitors of Influenza Virus H3N2 Hemagglutinin: Insights from Molecular Dynamics Simulation," International Journal of Chemical Engineering and Applications vol. 15, no. 2, pp. 60-63, 2024.
