Please use this identifier to cite or link to this item: http://hdl.handle.net/10995/103110
Title: Antiviral effect of novel purine conjugate LAS-131 against Herpes simplex virus type 1 (Herpesviridae: Alphaherpesvirinae: Simplexvirus: Human alphaherpesvirus 1) in vitro
Антивирусный эффект нового конъюгата пурина LAS-131 в отношении вируса простого герпеса 1 типа (Herpesviridae: Alphaherpesvirinae: Simplexvirus: Human alphaherpesvirus 1) in vitro
Authors: Andronova, V. L.
Galegov, G. A.
Musiyak, V. V.
Vozdvizhenskaya, O. A.
Levit, G. L.
Krasnov, V. P.
Issue Date: 2021
Publisher: FBSI Central Research Institute of Epidemiology of Rospotrebnadzor
Citation: Antiviral effect of novel purine conjugate LAS-131 against Herpes simplex virus type 1 (Herpesviridae: Alphaherpesvirinae: Simplexvirus: Human alphaherpesvirus 1) in vitro / V. L. Andronova, G. A. Galegov, V. V. Musiyak, et al. — DOI 10.36233/0507-4088-2020-65-6-8 // Voprosy Virusologii. — 2021. — Vol. 65. — Iss. 6. — P. 373-380.
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,. © 2020 Izdatel'stvo Meditsina. All rights reserved.
Keywords: HERPES SIMPLEX VIRUS
IN VITRO ANTIVIRAL ACTIVITY
MECHANISM OF ACTION
TIME-OF-ADDITION ASSAY
ACICLOVIR
LAS 131
PURINE
UNCLASSIFIED DRUG
VIRUS DNA
ANTIVIRAL ACTIVITY
ARTICLE
CELL CULTURE
HUMAN ALPHAHERPESVIRUS 1
IN VITRO STUDY
LIFE CYCLE
NONHUMAN
VIRUS LOAD
VIRUS REPLICATION
URI: http://hdl.handle.net/10995/103110
Access: info:eu-repo/semantics/openAccess
SCOPUS ID: 85100305096
PURE ID: 20522584
a11298b0-b7d4-45d8-98a5-27536e0956b0
ISSN: 5074088
DOI: 10.36233/0507-4088-2020-65-6-8
Appears in Collections:Научные публикации, проиндексированные в SCOPUS и WoS CC

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