Computational study of binding of oseltamivir to neuraminidase mutants of influenza A virus

Muhammad Arba, Sri Wahyuli, Setyanto Tri Wahyudi, Amir Karton, Chun Wu

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)239-254
Number of pages16
JournalJournal of Applied Pharmaceutical Science
Volume14
Issue number2
DOIs
StatePublished - Feb 2024
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • General Pharmacology, Toxicology and Pharmaceutics
  • Pharmacology (medical)

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