TY  - JOUR
TI  - Rationally derived inhibitors of hepatitis C virus (HCV) p7 channel activity reveal prospect for bimodal antiviral therapy
AU  - Shaw, Joseph
AU  - Gosain, Rajendra
AU  - Kalita, Monoj Mon
AU  - Foster, Toshana L
AU  - Kankanala, Jayakanth
AU  - Mahato, D Ram
AU  - Abas, Sonia
AU  - King, Barnabas J
AU  - Scott, Claire
AU  - Brown, Emma
AU  - Bentham, Matthew J
AU  - Wetherill, Laura
AU  - Bloy, Abigail
AU  - Samson, Adel
AU  - Harris, Mark
AU  - Mankouri, Jamel
AU  - Rowlands, David J
AU  - Macdonald, Andrew
AU  - Tarr, Alexander W
AU  - Fischer, Wolfgang B
AU  - Foster, Richard
AU  - Griffin, Stephen
A2  - Brinkmann, Melanie M
A2  - Boudker, Olga
A2  - Gerold, Gisa
VL  - 9
PY  - 2020
DA  - 2020/11/10
SP  - e52555
C1  - eLife 2020;9:e52555
DO  - 10.7554/eLife.52555
UR  - https://doi.org/10.7554/eLife.52555
AB  - 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.
KW  - hepatitis c virus
KW  - p7
KW  - viroporin
KW  - antiviral drugs
KW  - virion egress
KW  - virus entry
JF  - eLife
SN  - 2050-084X
PB  - eLife Sciences Publications, Ltd
ER  -  <a href="http://www.asadoresteatre.com/">&#31649;&#23478;&#23110;&#26399;&#26399;&#20934;&#20813;&#36153;&#36164;&#26009;&#31934;&#36873;</a>
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