@article {10.7554/eLife.52555, article_type = {journal}, title = {Rationally derived inhibitors of hepatitis C virus (HCV) p7 channel activity reveal prospect for bimodal antiviral therapy}, author = {Shaw, Joseph and Gosain, Rajendra and Kalita, Monoj Mon and Foster, Toshana L and Kankanala, Jayakanth and Mahato, D Ram and Abas, Sonia and King, Barnabas J and Scott, Claire and Brown, Emma and Bentham, Matthew J and Wetherill, Laura and Bloy, Abigail and Samson, Adel and Harris, Mark and Mankouri, Jamel and Rowlands, David J and Macdonald, Andrew and Tarr, Alexander W and Fischer, Wolfgang B and Foster, Richard and Griffin, Stephen}, editor = {Brinkmann, Melanie M and Boudker, Olga and Gerold, Gisa}, volume = 9, year = 2020, month = {nov}, pub_date = {2020-11-10}, pages = {e52555}, citation = {eLife 2020;9:e52555}, doi = {10.7554/eLife.52555}, url = {https://doi.org/10.7554/eLife.52555}, abstract = {Since the 1960s, a single class of agent has been licensed targeting virus-encoded ion channels, or ‘viroporinsâ€? 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.}, keywords = {hepatitis c virus, p7, viroporin, antiviral drugs, virion egress, virus entry}, journal = {eLife}, issn = {2050-084X}, publisher = {eLife Sciences Publications, Ltd}, } 管家婆期期准免费资料精选