Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Selection of influenza virus resistant to the novel camphor-based antiviral camphecene results in loss of pathogenicity. / Zarubaev, Vladimir V.; Pushkina, Ekaterina A.; Borisevich, Sophia S. и др.
в: Virology, Том 524, 01.11.2018, стр. 69-77.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - Selection of influenza virus resistant to the novel camphor-based antiviral camphecene results in loss of pathogenicity
AU - Zarubaev, Vladimir V.
AU - Pushkina, Ekaterina A.
AU - Borisevich, Sophia S.
AU - Galochkina, Anastasia V.
AU - Garshinina, Angelica V.
AU - Shtro, Anna A.
AU - Egorova, Anna A.
AU - Sokolova, Anastasia S.
AU - Khursan, Sergey L.
AU - Yarovaya, Olga I.
AU - Salakhutdinov, Nariman F.
N1 - Publisher Copyright: © 2018 Elsevier Inc.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - 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.
AB - 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.
KW - Antivirals
KW - Camphecene
KW - Drug resistance
KW - Hemagglutinin
KW - Influenza virus
KW - Pathogenicity
UR - http://www.scopus.com/inward/record.url?scp=85052336245&partnerID=8YFLogxK
U2 - 10.1016/j.virol.2018.08.011
DO - 10.1016/j.virol.2018.08.011
M3 - Article
AN - SCOPUS:85052336245
VL - 524
SP - 69
EP - 77
JO - Virology
JF - Virology
SN - 0042-6822
ER -
ID: 16232666