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West Nile Virus Drug Discovery
Novartis Institute for Tropical Diseases, 10 Biopolis Road, Chromos 05-01, Singapore 138670, Singapore
* Author to whom correspondence should be addressed.
Received: 3 October 2013; in revised form: 25 November 2013 / Accepted: 25 November 2013 / Published: 3 December 2013
Abstract: The outbreak of West Nile virus (WNV) in 1999 in the USA, and its continued spread throughout the Americas, parts of Europe, the Middle East and Africa, underscored the need for WNV antiviral development. Here, we review the current status of WNV drug discovery. A number of approaches have been used to search for inhibitors of WNV, including viral infection-based screening, enzyme-based screening, structure-based virtual screening, structure-based rationale design, and antibody-based therapy. These efforts have yielded inhibitors of viral or cellular factors that are critical for viral replication. For small molecule inhibitors, no promising preclinical candidate has been developed; most of the inhibitors could not even be advanced to the stage of hit-to-lead optimization due to their poor drug-like properties. However, several inhibitors developed for related members of the family Flaviviridae, such as dengue virus and hepatitis C virus, exhibited cross-inhibition of WNV, suggesting the possibility to re-purpose these antivirals for WNV treatment. Most promisingly, therapeutic antibodies have shown excellent efficacy in mouse model; one of such antibodies has been advanced into clinical trial. The knowledge accumulated during the past fifteen years has provided better rationale for the ongoing WNV and other flavivirus antiviral development.
Keywords: drug discovery; antiviral; West Nile virus; flavivirus
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MDPI and ACS Style
Lim, S.P.; Shi, P.-Y. West Nile Virus Drug Discovery. Viruses 2013, 5, 2977-3006.
Lim SP, Shi P-Y. West Nile Virus Drug Discovery. Viruses. 2013; 5(12):2977-3006.
Lim, Siew P.; Shi, Pei-Yong. 2013. "West Nile Virus Drug Discovery." Viruses 5, no. 12: 2977-3006.