• Something wrong with this record ?

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

V. Gejji, P. Svoboda, M. Stefanik, H. Wang, J. Salat, L. Eyer, D. Ruzek, S. Fernando,

. 2020 ; 546 (-) : 13-19. [pub] 20200325

Language English Country United States

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc20028074

Grant support
NV16-34238A MZ0 CEP Register

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.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc20028074
003      
CZ-PrNML
005      
20230808134205.0
007      
ta
008      
210105s2020 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1016/j.virol.2020.03.006 $2 doi
035    __
$a (PubMed)32452412
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Gejji, Varun $u Department of Biological and Agricultural Engineering, Texas A&M University, College Station, United States.
245    13
$a An RNA-dependent RNA polymerase inhibitor for tick-borne encephalitis virus / $c V. Gejji, P. Svoboda, M. Stefanik, H. Wang, J. Salat, L. Eyer, D. Ruzek, S. Fernando,
520    9_
$a 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.
650    _2
$a zvířata $7 D000818
650    _2
$a antivirové látky $x farmakologie $7 D000998
650    _2
$a viry klíšťové encefalitidy $x účinky léků $x enzymologie $x genetika $7 D004669
650    _2
$a klíšťová encefalitida $x virologie $7 D004675
650    _2
$a inhibitory enzymů $x farmakologie $7 D004791
650    _2
$a lidé $7 D006801
650    _2
$a RNA-dependentní RNA-polymerasa $x antagonisté a inhibitory $x genetika $x metabolismus $7 D012324
650    _2
$a klíšťata $x virologie $7 D013987
650    _2
$a virové proteiny $x antagonisté a inhibitory $x genetika $x metabolismus $7 D014764
650    _2
$a replikace viru $x účinky léků $7 D014779
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Svoboda, Pavel $u Department of Virology, Veterinary Research Institute, Hudcova 70, CZ-62100, Brno, Czech Republic.
700    1_
$a Stefanik, Michal $u Department of Virology, Veterinary Research Institute, Hudcova 70, CZ-62100, Brno, Czech Republic; Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00, Brno, Czech Republic.
700    1_
$a Wang, Haoqi $u Department of Biological and Agricultural Engineering, Texas A&M University, College Station, United States.
700    1_
$a Salat, Jiri $u Department of Virology, Veterinary Research Institute, Hudcova 70, CZ-62100, Brno, Czech Republic.
700    1_
$a Eyer, Luděk $u Department of Virology, Veterinary Research Institute, Hudcova 70, CZ-62100, Brno, Czech Republic; Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branisovska 31, CZ-37005, Ceske Budejovice, Czech Republic. $7 xx0098551
700    1_
$a Růžek, Daniel, $u Department of Virology, Veterinary Research Institute, Hudcova 70, CZ-62100, Brno, Czech Republic; Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, Branisovska 31, CZ-37005, Ceske Budejovice, Czech Republic. $d 1981- $7 stk2008441707
700    1_
$a Fernando, Sandun $u Department of Biological and Agricultural Engineering, Texas A&M University, College Station, United States. Electronic address: sfernando@tamu.edu.
773    0_
$w MED00010745 $t Virology $x 1096-0341 $g Roč. 546, č. - (2020), s. 13-19
856    41
$u https://pubmed.ncbi.nlm.nih.gov/32452412 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20210105 $b ABA008
991    __
$a 20230808134202 $b ABA008
999    __
$a ok $b bmc $g 1608409 $s 1119254
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2020 $b 546 $c - $d 13-19 $e 20200325 $i 1096-0341 $m Virology $n Virology $x MED00010745
GRA    __
$a NV16-34238A $p MZ0
LZP    __
$a Pubmed-20210105

Find record

Citation metrics

Archiving options