Insights into binding molecular mechanism of hemagglutinin H3N2 of influenza virus complexed with arbidol and its derivative: A molecular dynamics simulation perspective
Issued Date
2022-12-01
Resource Type
ISSN
14769271
Scopus ID
2-s2.0-85138441274
Pubmed ID
36049355
Journal Title
Computational Biology and Chemistry
Volume
101
Rights Holder(s)
SCOPUS
Bibliographic Citation
Computational Biology and Chemistry Vol.101 (2022)
Suggested Citation
Boonma T., Soikudrua N., Nutho B., Rungrotmongkol T., Nunthaboot N. Insights into binding molecular mechanism of hemagglutinin H3N2 of influenza virus complexed with arbidol and its derivative: A molecular dynamics simulation perspective. Computational Biology and Chemistry Vol.101 (2022). doi:10.1016/j.compbiolchem.2022.107764 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/83529
Title
Insights into binding molecular mechanism of hemagglutinin H3N2 of influenza virus complexed with arbidol and its derivative: A molecular dynamics simulation perspective
Author's Affiliation
Other Contributor(s)
Abstract
Recently, the H3N2 influenza outbreak has caused serious global public health concern for future control of the next influenza pandemic. Since using current anti-influenza drugs targeting neuraminidase (oseltamivir and zanamivir) and the proton M2 channel (amantadine and rimantadine) leads to drug resistance, it is essential to seek new anti-viral agents that act on additional viral targets. Hemagglutinin (HA), a glycoprotein embedded in the viral surface and playing a critical role in influenza the viral replication cycle has become an attractive target. This work investigates the molecular binding mechanism of HA H3N2 of influenza virus complexed with the fusion inhibitor, arbidol and its derivative (der-arbidol), by means of molecular dynamics simulation. The result showed that the arbidol derivative could form many and strong hydrogen bonds with the HA surrounding amino acids comprising GLU1032(1), LYS3071(1) and LYS3102(1) while arbidol makes this type of interaction with only LYS582(1). The introduction of hydroxyl group at the meta-position of the thiophenol ring was detected to replace the nearby water molecule, thus allowing the direct hydrogen bond formation between der-arbidol and GLU1032(1) of HA residue. Furthermore, the salt bridge networks established among residues GLU572(1)···ARG542(1)···GLU972(2) were considerably more stable in HA-Der-arbidol than that found in HA-Arbidol. The predicted protein-ligand binding free energies were in agreement with experimental data indicating that der-arbidol exhibits higher inhibitory potency against HA H3N2 of influenza virus. Detailed information could be useful for further designing and optimizing HA fusion inhibitors with improved efficiency.