Document Type
Article
Version Deposited
Published Version
Publication Date
2-5-2024
Publication Title
Journal of Applied Pharmaceutical Science
DOI
10.7324/JAPS.2024.147448
Abstract
Oseltamivir (OTV), which targets the neuraminidase (NA) of Influenza A virus (IAV), has been reported to develop resistance. Here, we performed a computational study on the binding modes of OTV in the wild-type and popular mutants of IAV NA (E119A, E119D, E119G, H274Y, I117T, I117V, I117V-E119A, K150N, N294S, R292K, V116A, and Y252H). The Arg118, Glu119, Asp151, Arg152, Glu276, Arg292, and Arg371 were identified as crucial interacting residues with the drug. The energy decomposition analysis showed that with few exceptions, the dispersion interaction is the dominant interaction, followed by the charge-transfer and polarization interactions. The affinities for OTV were greatly reduced in all mutant systems, particularly in R292K and Y252H. The present study may be substantial in the design of new OTV analogs with better affinities to overcome the present drug resistance.
Recommended Citation
Arba M, Wahyuli S, Wahyudi ST, Karton A, Wu C. Computational study of binding of oseltamivir to neuraminidase mutants of influenza A virus. J Appl Pharm Sci. 2024;14(02):239–254. http://doi.org/10.7324/JAPS.2024.147448
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Comments
© The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.