Since the 1960s, a single class of agent has been licensed targeting virus-encoded ion channels, or 'viroporins', contrasting the success of channel blocking drugs in other areas of medicine. Although resistance arose to these prototypic adamantane inhibitors of the influenza A virus (IAV) M2 proton channel, a growing number of clinically and economically important viruses are now recognised to encode essential viroporins providing potential targets for modern drug discovery. We describe the first rationally designed viroporin inhibitor with a comprehensive structure-activity relationship (SAR). This step-change in understanding not only revealed a second biological function for the p7 viroporin from hepatitis C virus (HCV) during virus entry, but also enabled the synthesis of a labelled tool compound that retained biological activity. Hence, p7 inhibitors (p7i) represent a unique class of HCV antiviral targeting both the spread and establishment of infection, as well as a precedent for future viroporin-targeted drug discovery.
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Joseph Shaw
Leeds Institute of Medical Research, School of Medicine, University of Leeds, Leeds, United Kingdom
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The authors declare that no competing interests exist.
Rajendra Gosein
School of Chemistry, University of Leeds, Leeds, United Kingdom
Competing interests
The authors declare that no competing interests exist.
Monoj Mon Kalita
Institute of Biophotonics, National Yang-Ming University, Taipei, Taiwan
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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