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Recent progress on phenotype-based discovery of dengue inhibitors

Yokokawa, Fumiaki (2020) Recent progress on phenotype-based discovery of dengue inhibitors. RSC Medicinal Chemistry.


Dengue fever is the world’s most prevalent mosquito-borne viral disease caused by the four serotypes of dengue viruses, which are widely spread throughout tropical and sub-tropical countries. There has been an urgent need to identify an effective and safe dengue inhibitor as a therapeutic and a prophylactic agent for dengue fever. Most clinically approved antiviral drugs for the treatment of human immunodeficiency syndrome-1 (HIV-1) and hepatitis C virus (HCV) target virally encoded enzymes such as protease or polymerase. Inhibitors of these enzymes were typically identified by target-based screening followed by optimization via structure-based design. However, due to the lack of success to date of research efforts to identify dengue protease and polymerase inhibitors, alternative strategies for anti-dengue drug discovery need to be considered. As a complementary approach to the target-based drug discovery, phenotypic screening is a strategy often used in identification of new chemical starting points with novel mechanism of action in the area of infectious diseases such as antibiotics, antivirals, and anti-parasitic agents. This article overviews recent reports of dengue phenotypic screens, and discusses phenotype-based hit-to-lead chemistry optimizations. Challenges and outlook of dengue phenotype-based lead discovery are discussed at the end of this article.

Item Type: Article
Keywords: dengue Phenotypic screen
Date Deposited: 22 Dec 2020 00:45
Last Modified: 22 Dec 2020 00:45