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

Journal Virology
ISSN: 0042-6822
Output data Year: 2018, Volume: 524, Pages: 69-77 Pages count : 9 DOI: 10.1016/j.virol.2018.08.011
Tags Influenza virus; Hemagglutinin; Antivirals; Camphecene; Drug resistance; Pathogenicity
Authors Zarubaev Vladimir V. 1 , Pushkina Ekaterina A. 2 , Borisevich Sophia S. 3 , Galochkina Anastasia V. 1 , Garshinina Angelica V. 1 , Shtro Anna A. 4 , Egorova Anna A. 4 , Sokolova Anastasia S. 5 , Khursan Sergey L. 3 , Yarovaya Olga I. 5,6 , Salakhutdinov Nariman F. 5,6
Affiliations
1 (Данные Web of science) Pasteur Inst Epidemiol & Microbiol, 14 Mira St, St Petersburg 197101, Russia
2 (Данные Web of science) St Petersburg State Univ, 7-9 Univ Skaya Nab, St Petersburg 199034, Russia
3 (Данные Web of science) Ufa Inst Chem, 71 Prospekt Oktyabrya, Ufa 450054, Russia
4 (Данные Web of science) Smorodintsev Res Inst Influenza, 15-17 Prof Popova St, St Petersburg 197376, Russia
5 (Данные Web of science) Russian Acad Sci, Siberian Branch, NN Vorozhtsov Novosibirsk Inst Organ Chem, 9 Lavrentjev Ave, Novosibirsk 630090, Russia
6 (Данные Web of science) Novosibirsk State Univ, 2 Pirogova St, Novosibirsk 630090, Russia

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.
Cite: Zarubaev V.V. , Pushkina E.A. , Borisevich S.S. , Galochkina A.V. , Garshinina A.V. , Shtro A.A. , Egorova A.A. , Sokolova A.S. , Khursan S.L. , Yarovaya O.I. , Salakhutdinov N.F.
Selection of influenza virus resistant to the novel camphor-based antiviral camphecene results in loss of pathogenicity
Virology. 2018. V.524. P.69-77. DOI: 10.1016/j.virol.2018.08.011 WOS Scopus РИНЦ
Files: Full text from publisher
Dates:
Published print: Nov 1, 2018
Identifiers:
Web of science WOS:000446415700007
Scopus 2-s2.0-85052336245
Elibrary 35758034
OpenAlex W2888962713
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