Selection of influenza virus resistant to the novel camphor-based antiviral camphecene results in loss of pathogenicity

Vladimir V. Zarubaev, Ekaterina A. Pushkina, Sophia S. Borisevich, Anastasia V. Galochkina, Angelica V. Garshinina, Anna A. Shtro, Anna A. Egorova, Anastasia S. Sokolova, Sergey L. Khursan, Olga I. Yarovaya, Nariman F. Salakhutdinov

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Due to the ability of influenza virus to develop drug resistance, the search for novel antivirals is an important goal of medical science and health care systems. We assessed the ability of the influenza virus to develop resistance to the hemagglutinin inhibitor camphecene and characterized laboratory-selected resistant strains. We showed by electron microscopy that camphecene decreases the number of virions fusing their envelopes with endosomal membranes. A 160-fold decrease in virus susceptibility was observed after six passages in cells. This was associated with the emergence of a V458L mutation in the HA2 subunit of HA and with a decrease in viral pathogenicity. Molecular modeling predicts that this substitution results in a more stable HA molecule compared to wild-type HA; and an altered camphecene-binding site. Therefore, despite the relatively rapid development of resistance, camphecene remains promising as a potential antiviral due to the low pathogenicity of resistant viruses that may arise.

Original languageEnglish
Pages (from-to)69-77
Number of pages9
JournalVirology
Volume524
DOIs
Publication statusPublished - 1 Nov 2018

Keywords

  • Antivirals
  • Camphecene
  • Drug resistance
  • Hemagglutinin
  • Influenza virus
  • Pathogenicity

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