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10.1128/AAC.02680-20 http://scihub22266oqcxt.onion/10.1128/AAC.02680-20 34097489!8370243!34097489     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Antimicrob+Agents+Chemother 2021 ; 65 (9): e0268020 Nephropedia Template TP {{tp|p=34097489|t=2021. Hepatitis C Virus Protease Inhibitors Show Differential Efficacy and Interactions with Remdesivir for Treatment of SARS-CoV-2 In Vitro |pdf=|usr=}}{{34097489}} gab.com Text Hepatitis C Virus Protease Inhibitors Show Differential Efficacy and Interactions with Remdesivir for Treatment of SARS-CoV-2 In Vitro JO: Antimicrob Agents Chemother http://www.kidney.de/pget.php?&tw=1&pmid=34097489 #FOAvip Antivirals targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could improve treatment of COVID-19. We evaluated the efficacy of clinically relevant hepatitis C virus (HCV) NS3 protease inhibitors (PIs) against SARS-CoV-2 and their interactions with remdesivir, the only direct-acting antiviral approved for COVID-19 treatment. HCV PIs showed differential potency in short-term treatment assays based on the detection of SARS-CoV-2 spike protein in Vero E6 cells. Linear PIs boceprevir, telaprevir, and narlaprevir had 50% effective concentrations (EC(50)) of approximately 40 muM. Among the macrocyclic PIs, simeprevir had the highest (EC(50), 15 muM) and glecaprevir the lowest (EC(50), >178 muM) potency, with paritaprevir, grazoprevir, voxilaprevir, vaniprevir, danoprevir, and deldeprevir in between. Acyclic PIs asunaprevir and faldaprevir had EC(50)s of 72 and 23 muM, respectively. ACH-806, inhibiting the HCV NS4A protease cofactor, had an EC(50) of 46 muM. Similar and slightly increased PI potencies were found in human hepatoma Huh7.5 cells and human lung carcinoma A549-hACE2 cells, respectively. Selectivity indexes based on antiviral and cell viability assays were highest for linear PIs. In short-term treatments, combination of macrocyclic but not linear PIs with remdesivir showed synergism in Vero E6 and A549-hACE2 cells. Longer-term treatment of infected Vero E6 and A549-hACE2 cells with 1-fold EC(50) PI revealed minor differences in the barrier to SARS-CoV-2 escape. Viral suppression was achieved with 3- to 8-fold EC(50) boceprevir or 1-fold EC(50) simeprevir or grazoprevir, but not boceprevir, in combination with 0.4- to 0.8-fold EC(50) remdesivir; these concentrations did not lead to viral suppression in single treatments. This study could inform the development and application of protease inhibitors for optimized antiviral treatments of COVID-19. Twit Text FOAVip Hepatitis C Virus Protease Inhibitors Show Differential Efficacy and Interactions with Remdesivir for Treatment of SARS-CoV-2 In Vitro ????Antimicrob Agents Chemother http://www.kidney.de/pget.php?&tw=1&pmid=34097489 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34097489 #FOAvip English Wikipedia <ref>{{Cite pmid|34097489}}</ref> Hepatitis C Virus Protease Inhibitors Show Differential Efficacy and Interactions with Remdesivir for Treatment of SARS-CoV-2 In Vitro #MMPMID34097489 Gammeltoft KA; Zhou Y; Duarte Hernandez CR; Galli A; Offersgaard A; Costa R; Pham LV; Fahnoe U; Feng S; Scheel TKH; Ramirez S; Bukh J; Gottwein JM Antimicrob Agents Chemother 2021[Aug]; 65 (9): e0268020 PMID34097489show ga Antivirals targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could improve treatment of COVID-19. We evaluated the efficacy of clinically relevant hepatitis C virus (HCV) NS3 protease inhibitors (PIs) against SARS-CoV-2 and their interactions with remdesivir, the only direct-acting antiviral approved for COVID-19 treatment. HCV PIs showed differential potency in short-term treatment assays based on the detection of SARS-CoV-2 spike protein in Vero E6 cells. Linear PIs boceprevir, telaprevir, and narlaprevir had 50% effective concentrations (EC(50)) of approximately 40 muM. Among the macrocyclic PIs, simeprevir had the highest (EC(50), 15 muM) and glecaprevir the lowest (EC(50), >178 muM) potency, with paritaprevir, grazoprevir, voxilaprevir, vaniprevir, danoprevir, and deldeprevir in between. Acyclic PIs asunaprevir and faldaprevir had EC(50)s of 72 and 23 muM, respectively. ACH-806, inhibiting the HCV NS4A protease cofactor, had an EC(50) of 46 muM. Similar and slightly increased PI potencies were found in human hepatoma Huh7.5 cells and human lung carcinoma A549-hACE2 cells, respectively. Selectivity indexes based on antiviral and cell viability assays were highest for linear PIs. In short-term treatments, combination of macrocyclic but not linear PIs with remdesivir showed synergism in Vero E6 and A549-hACE2 cells. Longer-term treatment of infected Vero E6 and A549-hACE2 cells with 1-fold EC(50) PI revealed minor differences in the barrier to SARS-CoV-2 escape. Viral suppression was achieved with 3- to 8-fold EC(50) boceprevir or 1-fold EC(50) simeprevir or grazoprevir, but not boceprevir, in combination with 0.4- to 0.8-fold EC(50) remdesivir; these concentrations did not lead to viral suppression in single treatments. This study could inform the development and application of protease inhibitors for optimized antiviral treatments of COVID-19. |*COVID-19 Drug Treatment[MESH] |*Hepatitis C, Chronic[MESH] |*Hepatitis C/drug therapy[MESH] |Adenosine Monophosphate/analogs & derivatives[MESH] |Alanine/analogs & derivatives[MESH] |Animals[MESH] |Antiviral Agents/pharmacology/therapeutic use[MESH] |Chlorocebus aethiops[MESH] |Hepacivirus[MESH] |Humans[MESH] |Protease Inhibitors/pharmacology/therapeutic use[MESH] |SARS-CoV-2[MESH] |Spike Glycoprotein, Coronavirus[MESH] |Vero Cells[MESH]Hepatitis C Virus Protease Inhibitors Show Differential Efficacy and I(epmc).pdf DeepDyve Pubget Overpricing