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10.1042/BST20200568 http://scihub22266oqcxt.onion/10.1042/BST20200568 33439253!7925013!33439253     free     free     free Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Biochem+Soc+Trans 2021 ; 49 (1): 281-295 Nephropedia Template TP {{tp|p=33439253|t=2021. Antivirals that target the host IMPalpha/beta1-virus interface |pdf=|usr=}}{{33439253}} gab.com Text Antivirals that target the host IMPalpha/beta1-virus interface JO: Biochem Soc Trans http://www.kidney.de/pget.php?&tw=1&pmid=33439253 #FOAvip Although transport into the nucleus mediated by the importin (IMP) alpha/beta1-heterodimer is central to viral infection, small molecule inhibitors of IMPalpha/beta1-dependent nuclear import have only been described and shown to have antiviral activity in the last decade. Their robust antiviral activity is due to the strong reliance of many different viruses, including RNA viruses such as human immunodeficiency virus-1 (HIV-1), dengue (DENV), and Zika (ZIKV), on the IMPalpha/beta1-virus interface. High-throughput compound screens have identified many agents that specifically target this interface. Of these, agents targeting IMPalpha/beta1 directly include the FDA-approved macrocyclic lactone ivermectin, which has documented broad-spectrum activity against a whole range of viruses, including HIV-1, DENV1-4, ZIKV, West Nile virus (WNV), Venezuelan equine encephalitis virus, chikungunya, and most recently, SARS-CoV-2 (COVID-19). Ivermectin has thus far been tested in Phase III human clinical trials for DENV, while there are currently close to 80 trials in progress worldwide for SARS-CoV-2; preliminary results for randomised clinical trials (RCTs) as well as observational/retrospective studies are consistent with ivermectin affording clinical benefit. Agents that target the viral component of the IMPalpha/beta1-virus interface include N-(4-hydroxyphenyl) retinamide (4-HPR), which specifically targets DENV/ZIKV/WNV non-structural protein 5 (NS5). 4-HPR has been shown to be a potent inhibitor of infection by DENV1-4, including in an antibody-dependent enhanced animal challenge model, as well as ZIKV, with Phase II clinical challenge trials planned. The results from rigorous RCTs will help determine the therapeutic potential of the IMPalpha/beta1-virus interface as a target for antiviral development. Twit Text FOAVip Antivirals that target the host IMPalpha/beta1-virus interface ????Biochem Soc Trans http://www.kidney.de/pget.php?&tw=1&pmid=33439253 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33439253 #FOAvip English Wikipedia <ref>{{Cite pmid|33439253}}</ref> Antivirals that target the host IMPalpha/beta1-virus interface #MMPMID33439253 Martin AJ; Jans DA Biochem Soc Trans 2021[Feb]; 49 (1): 281-295 PMID33439253show ga Although transport into the nucleus mediated by the importin (IMP) alpha/beta1-heterodimer is central to viral infection, small molecule inhibitors of IMPalpha/beta1-dependent nuclear import have only been described and shown to have antiviral activity in the last decade. Their robust antiviral activity is due to the strong reliance of many different viruses, including RNA viruses such as human immunodeficiency virus-1 (HIV-1), dengue (DENV), and Zika (ZIKV), on the IMPalpha/beta1-virus interface. High-throughput compound screens have identified many agents that specifically target this interface. Of these, agents targeting IMPalpha/beta1 directly include the FDA-approved macrocyclic lactone ivermectin, which has documented broad-spectrum activity against a whole range of viruses, including HIV-1, DENV1-4, ZIKV, West Nile virus (WNV), Venezuelan equine encephalitis virus, chikungunya, and most recently, SARS-CoV-2 (COVID-19). Ivermectin has thus far been tested in Phase III human clinical trials for DENV, while there are currently close to 80 trials in progress worldwide for SARS-CoV-2; preliminary results for randomised clinical trials (RCTs) as well as observational/retrospective studies are consistent with ivermectin affording clinical benefit. Agents that target the viral component of the IMPalpha/beta1-virus interface include N-(4-hydroxyphenyl) retinamide (4-HPR), which specifically targets DENV/ZIKV/WNV non-structural protein 5 (NS5). 4-HPR has been shown to be a potent inhibitor of infection by DENV1-4, including in an antibody-dependent enhanced animal challenge model, as well as ZIKV, with Phase II clinical challenge trials planned. The results from rigorous RCTs will help determine the therapeutic potential of the IMPalpha/beta1-virus interface as a target for antiviral development. |Animals[MESH] |Antiviral Agents/pharmacology[MESH] |Humans[MESH] |Ivermectin/*pharmacology[MESH] |Protein Binding/drug effects[MESH] |Viral Nonstructural Proteins/*metabolism[MESH] |Virus Diseases/metabolism/*prevention & control/virology[MESH] |Viruses/*metabolism/pathogenicity[MESH] |alpha Karyopherins/*metabolism[MESH]Antivirals that target the host IMPalpha/beta1-virus interface (epmc).pdf DeepDyve Pubget Overpricing