Antiviral effect of novel purine conjugate LAS-131 against Herpes simplex virus type 1 (Herpesviridae: Alphaherpesvirinae: Simplexvirus: Human alphaherpesvirus 1) in vitro
- Authors: Andronova V.L.1, Galegov G.A.1, Musiyak V.V.2, Vozdvizhenskaya O.A.2, Levit G.L.2, Krasnov V.P.2,3
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Affiliations:
- FSBI «National Research Center of Epidemiology and Microbiology named after honorary academician N.F. Gamaleya» of the Ministry of Health of Russia
- FSBIS I.Ya. Postovsky Institute of Organic Synthesis of the Ural Branch of the Russian Academy of Sciences
- FSAEI HE «Ural Federal University named after the First President of Russia B.N. Yeltsin»
- Issue: Vol 65, No 6 (2020)
- Pages: 373-380
- Section: ORIGINAL RESEARCH
- URL: https://journals.rcsi.science/0507-4088/article/view/118166
- DOI: https://doi.org/10.36233/0507-4088-2020-65-6-8
- ID: 118166
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Abstract
Introduction. Herpes simplex viruses type 1 (HSV-1) are extremely widespread throughout the world and, similar to other herpesviruses, establish lifelong persistent infection in the host. Reactivating sporadically, HSV-1 elicits recurrences in both immunocompetent and immunocompromised individuals and can cause serious diseases (blindness, encephalitis, generalized infections). The currently available antiherpetic drugs that aimed mainly at suppressing replication of viral DNA are not always effective enough, for example, due to the development of drug resistance. As we showed earlier the newly discovered compound LAS-131 exhibits the strong and highly selective inhibitory activity against HSV‑1, including strain resistant to acyclovir (selective index, SI = 63). The presence of LAS-131 at a concentration of 20 μg/ml leads to a decrease in the titer of HSV-1 (strain L2) by 4 lg in a one round of HSV-1 replication.
Material and methods. To establish the step(s) of the virus life cycle that is sensitive to the action of LAS-131, we have applied a widely used approach, that made it possible to determine how long the addition of a compound can be postponed before it loses its antiviral activity (time-of-addition assay), and to compare this indicator with the crucial time of application of inhibitors with a well-known mechanism of action (in cell culture).
Results. It has been shown for the first time that LAS-131 retains a pronounced antiviral effect when introduced into the experimental system no later than 9 hours post-infection (p.i.). However, LAS-131 does not affect the release of HSV-1 from the cell.
Discussion. Together with published data on the termination of the synthesis of viral DNA 9–12 h after the adsorption in a cell culture infected with HSV with a high multiplicity (≥1 PFU/cell), our results suggest that LAS-131 interferes the life cycle of HSV-1 during synthesis of viral DNA. Further studies of the mechanism of action are necessary to establish definitely the biological target for this compound,.
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##article.viewOnOriginalSite##About the authors
V. L. Andronova
FSBI «National Research Center of Epidemiology and Microbiology named after honorary academician N.F. Gamaleya» of the Ministry of Health of Russia
Author for correspondence.
Email: andronova.vl@yandex.ru
Ph.D.(Biol.), Leading Researcher of the Laboratory for Molecular Pathogenesis of Chronic Viral Infections, Institute of Virology named after D.I. Ivanovsky
123098, Moscow
Russian FederationG. A. Galegov
FSBI «National Research Center of Epidemiology and Microbiology named after honorary academician N.F. Gamaleya» of the Ministry of Health of Russia
Email: g.galegov@yandex.ru
P.D., D.Sci.(Biol.), Professor, Head of the Laboratory for Molecular Pathogenesis of Chronic Viral Infections, Institute of Virology named after D.I. Ivanovsky
123098, Moscow
Russian FederationV. V. Musiyak
FSBIS I.Ya. Postovsky Institute of Organic Synthesis of the Ural Branch of the Russian Academy of Sciences
Email: vvmusiyak@ios.uran.ru
Ph.D.(Chem.), researcher of the Laboratory of Asymmetric Synthesis
620108, Ekaterinburg
Russian FederationO. A. Vozdvizhenskaya
FSBIS I.Ya. Postovsky Institute of Organic Synthesis of the Ural Branch of the Russian Academy of Sciences
Email: olgavozdv@mail.ru
Junior Researcher of the Laboratory of Asymmetric Synthesis
620108, Ekaterinburg
Ph.D., D.Sci.(Chem.), Leading researcher of the Laboratory of Asymmetric Synthesis Russian FederationG. L. Levit
FSBIS I.Ya. Postovsky Institute of Organic Synthesis of the Ural Branch of the Russian Academy of Sciences
Email: ca512@ios.uran.ru
Ph.D., D.Sci.(Chem.), Leading researcher of the Laboratory of Asymmetric Synthesis
620108, Ekaterinburg
Russian FederationV. P. Krasnov
FSBIS I.Ya. Postovsky Institute of Organic Synthesis of the Ural Branch of the Russian Academy of Sciences; FSAEI HE «Ural Federal University named after the First President of Russia B.N. Yeltsin»
Email: ca@ios.uran.ru
Ph.D., D.Sci.(Chem.), Prof., Head of the Laboratory of Asymmetric Synthesis; Researcher of the research laboratory of medical chemistry and advanced organic materials, the Institute of Chemistry and Technology
620108, Ekaterinburg
620002 Ekaterinburg
Russian FederationReferences
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