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@article{1494116,
author = {Eyer, Luděk and Fojtíková, Martina and Nencka, Radim and Rudolf, Ivo and Hubálek, Zdeněk and Růžek, Daniel},
article_location = {Washington, D.C.},
article_number = {3},
doi = {http://dx.doi.org/10.1128/AAC.02093-18},
keywords = {West Nile virus; antiviral agents; flavivirus; nucleoside analogs},
language = {eng},
issn = {0066-4804},
journal = {ANTIMICROBIAL AGENTS AND CHEMOTHERAPY},
title = {Viral RNA-dependent RNA polymerase inhibitor 7-deaza-2'-C-methyladenosine prevents death in a mouse model of West Nile virus infection},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395895/},
volume = {63},
year = {2019}
}
TY - JOUR
ID - 1494116
AU - Eyer, Luděk - Fojtíková, Martina - Nencka, Radim - Rudolf, Ivo - Hubálek, Zdeněk - Růžek, Daniel
PY - 2019
TI - Viral RNA-dependent RNA polymerase inhibitor 7-deaza-2'-C-methyladenosine prevents death in a mouse model of West Nile virus infection
JF - ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
VL - 63
IS - 3
SP - 1-14
EP - 1-14
PB - AMER SOC MICROBIOLOGY
SN - 00664804
KW - West Nile virus
KW - antiviral agents
KW - flavivirus
KW - nucleoside analogs
UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395895/
L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395895/
N2 - West Nile virus (WNV) is a medically important emerging arbovirus causing serious neuroinfections in humans and against which no approved antiviral therapy is currently available. In this study, we demonstrate that 2=-C-methyl- or 4=-azido-modified nucleosides are highly effective inhibitors of WNV replication, showing nanomolar or low micromolar anti-WNV activity and negligible cytotoxicity in cell culture. One representative of C2=-methylated nucleosides, 7-deaza-2=-Cmethyladenosine, significantly protected WNV-infected mice from disease progression and mortality. Twice daily treatment at 25 mg/kg starting at the time of infection resulted in 100% survival of the mice. This compound was highly effective, even if the treatment was initiated 3 days postinfection, at the time of a peak of viremia, which resulted in a 90% survival rate. However, the antiviral effect of 7-deaza-2=-Cmethyladenosine was absent or negligible when the treatment was started 8 days postinfection (i.e., at the time of extensive brain infection). The 4=-azido moiety appears to be another important determinant for highly efficient inhibition of WNV replication in vitro. However, the strong anti-WNV effect of 4=-azidocytidine and 4=- azido-aracytidine was cell type dependent and observed predominantly in porcine kidney stable (PS) cells. The effect was much less pronounced in Vero cells. Our results indicate that 2=-C-methylated or 4=-azidated nucleosides merit further investigation as potential therapeutic agents for treating WNV infections as well as infections caused by other medically important flaviviruses.
ER -
EYER, Luděk, Martina FOJTÍKOVÁ, Radim NENCKA, Ivo RUDOLF, Zdeněk HUBÁLEK a Daniel RŮŽEK. Viral RNA-dependent RNA polymerase inhibitor 7-deaza-2'-C-methyladenosine prevents death in a mouse model of West Nile virus infection. \textit{ANTIMICROBIAL AGENTS AND CHEMOTHERAPY}. Washington, D.C.: AMER SOC MICROBIOLOGY, 2019, roč.~63, č.~3, s.~1-14. ISSN~0066-4804. Dostupné z: https://dx.doi.org/10.1128/AAC.02093-18.
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