Broad range of inhibiting action of novel camphor-based compound with anti-hemagglutinin activity against influenza viruses in vitro and in vivo

Broad range of inhibiting action of novel camphor-based compound with anti-hemagglutinin activity against influenza viruses in vitro and in vivo Научная публикация

Журнал

Antiviral Research
ISSN: 0166-3542 , E-ISSN: 1872-9096

Вых. Данные

Год: 2015, Том: 120, Страницы: 126-133 Страниц : DOI: 10.1016/j.antiviral.2015.06.004

Ключевые слова

Influenza; Antivirals; Hemagglutinin; Cage compounds; Camphor derivatives

Авторы

Zarubaev V. V. ¹ , Garshinina A. V. ¹ , Tretiak T. S. ¹ , Fedorova V. A. ¹ , Shtro A. A. ¹ , Sokolova A. S. ^2,3 , Yarovaya O. I. ^2,3 , Salakhutdinov N. F. ^2,3

Организации

1	(Данные Web of science) Influenza Res Inst, St Petersburg 197376, Russia
2	(Данные Web of science) Russian Acad Sci, Siberian Branch, NN Vorozhtsov Novosibirsk Inst Organ Chem, Novosibirsk 630090, Russia
3	(Данные Web of science) Novosibirsk State Univ, Novosibirsk 630090, Russia

Influenza virus continues to remain one of the leading human respiratory pathogens causing significant morbidity and mortality around the globe. Due to short-term life cycle and high rate of mutations influenza virus is able to rapidly develop resistance to clinically available antivirals. This makes necessary the search and development of new drugs with different targets and mechanisms of activity. Here we report anti-influenza activity of camphor derivative 1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene-aminoetha nol (camphecene). In in vitro experiments it inhibited influenza viruses A(H1, Hlpdm09, H3 and H5 subtypes) and B with EC50's lying in micromolar range. Due to low cytotoxicity it resulted in high selectivity indices (74-661 depending on the virus). This effect did not depend on susceptibility or resistance of the viruses to adamantane derivatives amantadine and rimantadine. The compound appeared the most effective when added at the early stages of viral life cycle (0-2 h p.i.). In direct hemagglutinin inhibition tests camphecene was shown to decrease the activity of HA's of influenza viruses A and B. The activity of camphecene was further confirmed in experiments with influenza virus-infected mice, in which, being used orally by therapeutic schedule (once a day, days 1-5 p.i.) it decreased specific mortality of animals infected with both influenza A and B viruses (highest indices of protection 66.7% and 88.9%, respectively). Taken together, these results are encouraging for further development of camphecene-based drug(s) and for exploration of camphor derivatives as highly prospective group of potential antivirals. (C) 2015 Elsevier B.V. All rights reserved.

Zarubaev V.V. , Garshinina A.V. , Tretiak T.S. , Fedorova V.A. , Shtro A.A. , Sokolova A.S. , Yarovaya O.I. , Salakhutdinov N.F.
Broad range of inhibiting action of novel camphor-based compound with anti-hemagglutinin activity against influenza viruses in vitro and in vivo
Antiviral Research. 2015. V.120. P.126-133. DOI: 10.1016/j.antiviral.2015.06.004 WOS Scopus РИНЦ

Опубликована в печати:

1 авг. 2015 г.

Web of science	WOS:000358099000017
Scopus	2-s2.0-84935836086
РИНЦ	23988462
OpenAlex	W625936381