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Issue 5, 2020
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Recent progress on phenotype-based discovery of dengue inhibitors

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Abstract

Dengue fever is the world's most prevalent mosquito-borne viral disease caused by the four serotypes of dengue virus, 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 mechanisms of action in the area of infectious diseases such as antibiotics, antivirals, and anti-parasitic agents. This article is an overview of recent reports on dengue phenotypic screens and discusses phenotype-based hit-to-lead chemistry optimization. The challenges encountered and the outlook on dengue phenotype-based lead discovery are discussed at the end of this article.

Graphical abstract: Recent progress on phenotype-based discovery of dengue inhibitors

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Article information


Submitted
15 Feb 2020
Accepted
24 Mar 2020
First published
20 Apr 2020

RSC Med. Chem., 2020,11, 541-551
Article type
Review Article

Recent progress on phenotype-based discovery of dengue inhibitors

F. Yokokawa, RSC Med. Chem., 2020, 11, 541
DOI: 10.1039/D0MD00052C

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