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An RNA-dependent RNA polymerase inhibitor for tick-borne encephalitis virus
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SYSNO ASEP 0537396 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title An RNA-dependent RNA polymerase inhibitor for tick-borne encephalitis virus Author(s) Gejji, V. (US)
Svoboda, P. (CZ)
Štefánik, M. (CZ)
Wang, H. (US)
Salát, J. (CZ)
Eyer, Luděk (BC-A) RID, ORCID
Růžek, Daniel (BC-A) RID, ORCID
Fernando, S. (US)Number of authors 8 Source Title Virology. - : Elsevier - ISSN 0042-6822
Roč. 546, JUL 2020 (2020), s. 13-19Number of pages 7 s. Publication form Print - P Language eng - English Country US - United States Keywords west-nile-virus ; methyltransferase ; identification ; immunization ; protein ; flaviviruses ; citicoline ; dynamics ; vaccine ; domain ; tbev ; Non-structural proteins ; Viral inhibition ; Molecular ; Simulation Subject RIV EE - Microbiology, Virology OECD category Microbiology R&D Projects NV16-34238A GA MZd - Ministry of Health (MZ) GA20-14325S GA ČR - Czech Science Foundation (CSF) Method of publishing Open access Institutional support BC-A - RVO:60077344 UT WOS 000536213500002 EID SCOPUS 85082941140 DOI 10.1016/j.virol.2020.03.006 Annotation Tick-borne encephalitis virus (TBEV) is a medically important representative of the Flaviviridae family. The TBEV genome encodes a single polyprotein, which is co/post-translationally cleaved into three structural and seven non-structural proteins. Of the non-structural proteins, NS5, contains an RNA-dependent RNA polymerase (RdRp) domain that is highly conserved and is responsible for the genome replication. Screening for potential antivirals was done using a hybrid receptor and ligand-based pharmacophore search likely targeting the RdRp domain. For the identification of pharmacophores, a mixture of small probe molecules and nucleotide triphosphates were used. The ligand/receptor interaction screenings of structures from the ZINC database resulted in five compounds. Zinc 3677 and 7151 exhibited lower cytotoxicity and were tested for their antiviral effect against TBEV in vitro. Zinc 3677 inhibited TBEV at micromolar concentrations. The results indicate that Zinc 3677 represents a good target for structure-activity optimizations leading potentially to a discovery of effective TBEV antivirals. Workplace Biology Centre (since 2006) Contact Dana Hypšová, eje@eje.cz, Tel.: 387 775 214 Year of Publishing 2021 Electronic address https://www.sciencedirect.com/science/article/pii/S0042682220300593?via%3Dihub
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