A diarylamine derived from anthranilic acid inhibits ZIKV replication

Abstract

Zika virus (ZIKV) is a mosquito-transmitted Flavivirus, originally identified in Uganda in 1947 and recently associated with a large outbreak in South America. Despite extensive efforts there are currently no approved antiviral compounds for treatment of ZIKV infection. Here we describe the antiviral activity of diarylamines derived from anthranilic acid (FAMs) against ZIKV. A synthetic FAM (E3) demonstrated anti-ZIKV potential by reducing viral replication up to 86%. We analyzed the possible mechanisms of action of FAM E3 by evaluating the intercalation of this compound into the viral dsRNA and its interaction with the RNA polymerase of bacteriophage SP6. However, FAM E3 did not act by these mechanisms. In silico results predicted that FAM E3 might bind to the ZIKV NS3 helicase suggesting that this protein could be one possible target of this compound. To test this, the thermal stability and the ATPase activity of the ZIKV NS3 helicase domain (NS3Hel) were investigated in vitro and we demonstrated that FAM E3 could indeed bind to and stabilize NS3Hel.

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Item Type:	Article
Authors/Creators:	Silva, S Shimizu, JF Oliveira, DMD Assis, LRD Bittar, C Mottin, M Sousa, BKDP Mesquita, NCDMR Regasini, LO Rahal, P Oliva, G Perryman, AL Ekins, S Andrade, CH Goulart, LR Sabino-Silva, R Merits, A Harris, M https://orcid.org/0000-0002-9821-1003 Jardim, ACG
Copyright, Publisher and Additional Information:	© The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Dates:	Accepted: 29 October 2019 Published (online): 27 November 2019 Published: 27 November 2019
Institution:	The University of Leeds
Academic Units:	The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Virology 1 (Leeds)
Depositing User:	Symplectic Publications
Date Deposited:	20 Dec 2019 10:18
Last Modified:	20 Dec 2019 10:18
Status:	Published
Publisher:	Nature Research
Identification Number:	10.1038/s41598-019-54169-z
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:154718

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A diarylamine derived from anthranilic acid inhibits ZIKV replication

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