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bioRxiv2025June 20, 2025Journal Article

Discovery of orally bioavailable Zika and West Nile Virus antiviral compounds targeting the NS2B-NS3 protease.

Nathaniel T Kenton1, Haim Barr2, Artem Cherepakha3, Lotte Coelmont4, Caroline Collard4, David Cousins5, Geraint H M Davies1, Oleksii Degtyarenko3, Andrew Dirksen1, Daniel Elbrecht1, Daren Fearon6, James Gayvert1, Edward Griffen5, Dirk Jochmans4, Suzanne Kaptein4, Pavlo Kliatskiy3, Artem Kochetkov3, Mykyta Kordubailo3, Noa Lahav2, Nir London2, Elke Maas4, Peter Marples6, Nataliya Nady1, Johan Neyts4, Luong Nguyen1, Xiaomin Ni7, Yuliia Ogorodnik3, Matthew C Robinson1, Carolina Turk Simpson1, Ihor Tarabara3, Anton Tkachenko3, Annette von Delft7, Frank von Delft6,7,8,9, Oleksandr Yakymenko3, Alpha A Lee1
1PostEra Inc, 1 Broadway, Cambridge MA 02142, USA.
2The Wohl Drug Discovery Institute of the Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot 7610001, Israel.
3Enamine Ltd., 78 Winston Churchill Street, 02094 Kyiv, Ukraine.
4Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Virology, Antiviral Drug & Vaccine Research Group, KU Leuven, Leuven, Belgium.
5MedChemica Consultancy Ltd, Macclesfield, Cheshire, SK11 6DU, UK.
6Diamond Light Source Ltd, Harwell Science and Innovation Campus, Didcot OX11 0QX, UK.
7Centre for Medicines Discovery, University of Oxford, Oxford OX3 7FZ, UK.
8Research Complex at Harwell, Harwell Science and Innovation Campus, Didcot, UK.
9Department of Biochemistry, University of Johannesburg, Auckland Park, Johannesburg 2006, South Africa.
PubMed PMC DOI PDF

Abstract

Flaviviruses are a class of pathogenic viruses with pandemic potential which are typically transmitted via infected arthropods. In particular, Zika virus is sexually transmissible and causes congenital malformations if infection occurs during pregnancy. Although over 1.5 million people were infected during the 2015-2016 Zika outbreak, to date, there are no clinical-stage vaccines or antivirals. He…

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