國家衛生研究院 NHRI:Item 3990099045/11894

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Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/11894

Title:	Nucleoside analogs with selective antiviral activity against dengue fever and Japanese encephalitis viruses
Authors:	Zandi, K;Bassit, L;Amblard, F;Cox, BD;Hassandarvish, P;Moghaddam, E;Yueh, A;Libanio Rodrigues, GO;Passos, I;Costa, VV;AbuBakar, S;Zhou, L;Kohler, J;Teixeira, MM;Schinazi, RF
Contributors:	Institute of Biotechnology and Pharmaceutical Research
Abstract:	Dengue virus (DENV) and Japanese Encephalitis virus (JEV) are two important arthropod-borne viruses from Flaviviridae family. DENV is a global public health problem with significant social and economic impacts especially in tropical and subtropical areas. JEV is a neurotropic arbovirus endemic to east and southeast Asia. There are no US FDA approved antiviral drugs available to treat or prevent DENV and JEV leaving nearly one-third of the worldwide population at risk for infection. Therefore, it is crucial to discover potent antiviral agents against these viruses. Nucleoside analogs as a class are widely used for the treatment of viral infections. In this study, we discovered nucleoside analogs that possess potent and selective anti-JEV and anti-DENV activity across all serotypes in cell-based assay systems. Both viruses were susceptible to sugar-substituted 2'-C-methyl analogs with either cytosine or 7-deaza-7-fluoro-adenine nucleobases. Mouse studies confirmed the anti-DENV activity of these nucleoside analogs. Molecular models were assembled for DENV serotype 2 (DENV-2) and JEV RNA-dependent RNA polymerase replication complexes bound to nucleotide inhibitors. These models show similarities between JEV and DENV-2 that recognize the same nucleotide inhibitors. Collectively, our findings provide promising compounds and structural rationale for the development of direct-acting antiviral agents with dual activity against JEV and DENV infections.
Date:	2019-07
Relation:	Antimicrobial Agents and Chemotherapy. 2019 Jul;63(7):e00397-19.
Link to:	http://dx.doi.org/10.1128/aac.00397-19
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0066-4804&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000472622600031
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85068174608
Appears in Collections:	[Yueh Andrew Yueh] Periodical Articles

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