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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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