An RNA-dependent RNA polymerase inhibitor for tick-borne encephalitis virus

0537396 - BC 2021 RIV US eng J - Journal Article
Gejji, V. - Svoboda, P. - Štefánik, M. - Wang, H. - Salát, J. - Eyer, Luděk - Růžek, Daniel - Fernando, S.
An RNA-dependent RNA polymerase inhibitor for tick-borne encephalitis virus.
Virology. Roč. 546, JUL 2020 (2020), s. 13-19. ISSN 0042-6822. E-ISSN 1089-862X
R&D Projects: GA MZd(CZ) NV16-34238A; GA ČR(CZ) GA20-14325S
Institutional support: RVO:60077344
Keywords : west-nile-virus * methyltransferase * identification * immunization * protein * flaviviruses * citicoline * dynamics * vaccine * domain * tbev * Non-structural proteins * Viral inhibition * Molecular * Simulation
OECD category: Microbiology
Impact factor: 3.616, year: 2020
Method of publishing: Open access
https://www.sciencedirect.com/science/article/pii/S0042682220300593?via%3Dihub

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.
Permanent Link: http://hdl.handle.net/11104/0315112