Molecules, Vol. 28, Pages 7375: Large Subunit of the Human Herpes Simplex Virus Terminase as a Promising Target in Design of Anti-Herpesvirus Agents

Molecules, Vol. 28, Pages 7375: Large Subunit of the Human Herpes Simplex Virus Terminase as a Promising Target in Design of Anti-Herpesvirus Agents Molecules doi: 10.3390/molecules28217375 Authors: Victor P. Krasnov Valeriya L. Andronova Alexander V. Belyavsky Sophia S. Borisevich George A. Galegov Oleg F. Kandarakov Dmitry A. Gruzdev Olga A. Vozdvizhenskaya Galina L. Levit Herpes simplex virus type 1 (HSV-1) is an extremely widespread pathogen characterized by recurrent infections. HSV-1 most commonly causes painful blisters or sores around the mouth or on the genitals, but it can also cause keratitis or, rarely, encephalitis. First-line and second-line antiviral drugs used to treat HSV infections, acyclovir and related compounds, as well as foscarnet and cidofovir, selectively inhibit herpesvirus DNA polymerase (DNA-pol). It has been previously found that (S)-4-[6-(purin-6-yl)aminohexanoyl]-7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine (compound 1) exhibits selective anti-herpesvirus activity against HSV-1 in cell culture, including acyclovir-resistant mutants, so we consider it as a lead compound. In this work, the selection of HSV-1 clones resistant to the lead compound was carried out. High-throughput sequencing of resistant clones and reference HSV-1/L2 parent strain was performed to identify the genetic determinants of the virus’s resistance to the lead compound. We identified a candidate mutation presumably associated wit...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research