|
Antiviral activity against HCV genotype 1b Con1 infected in human HuH7 cells assessed as inhibition of viral RNA replication after 3 days by renilla luciferase reporter gene assay in presence of human serum
|
Hepatitis C virus (isolate Con1)
|
0.027
nM
|
|
Journal : J. Med. Chem.
Title : Discovery of ledipasvir (GS-5885): a potent, once-daily oral NS5A inhibitor for the treatment of hepatitis C virus infection.
Year : 2014
Volume : 57
Issue : 5
First Page : 2033
Last Page : 2046
Authors : Link JO, Taylor JG, Xu L, Mitchell M, Guo H, Liu H, Kato D, Kirschberg T, Sun J, Squires N, Parrish J, Keller T, Yang ZY, Yang C, Matles M, Wang Y, Wang K, Cheng G, Tian Y, Mogalian E, Mondou E, Cornpropst M, Perry J, Desai MC.
Abstract : A new class of highly potent NS5A inhibitors with an unsymmetric benzimidazole-difluorofluorene-imidazole core and distal [2.2.1]azabicyclic ring system was discovered. Optimization of antiviral potency and pharmacokinetics led to the identification of 39 (ledipasvir, GS-5885). Compound 39 (GT1a replicon EC50 = 31 pM) has an extended plasma half-life of 37-45 h in healthy volunteers and produces a rapid >3 log viral load reduction in monotherapy at oral doses of 3 mg or greater with once-daily dosing in genotype 1a HCV-infected patients. 39 has been shown to be safe and efficacious, with SVR12 rates up to 100% when used in combination with direct-acting antivirals having complementary mechanisms.
|
Antiviral activity against HCV genotype 1a H77 infected in human HuH7 cells assessed as inhibition of viral RNA replication after 3 days by renilla luciferase reporter gene assay in presence of 10% BSA
|
Hepatitis C virus (isolate H77)
|
0.21
nM
|
|
Journal : J. Med. Chem.
Title : Discovery of ledipasvir (GS-5885): a potent, once-daily oral NS5A inhibitor for the treatment of hepatitis C virus infection.
Year : 2014
Volume : 57
Issue : 5
First Page : 2033
Last Page : 2046
Authors : Link JO, Taylor JG, Xu L, Mitchell M, Guo H, Liu H, Kato D, Kirschberg T, Sun J, Squires N, Parrish J, Keller T, Yang ZY, Yang C, Matles M, Wang Y, Wang K, Cheng G, Tian Y, Mogalian E, Mondou E, Cornpropst M, Perry J, Desai MC.
Abstract : A new class of highly potent NS5A inhibitors with an unsymmetric benzimidazole-difluorofluorene-imidazole core and distal [2.2.1]azabicyclic ring system was discovered. Optimization of antiviral potency and pharmacokinetics led to the identification of 39 (ledipasvir, GS-5885). Compound 39 (GT1a replicon EC50 = 31 pM) has an extended plasma half-life of 37-45 h in healthy volunteers and produces a rapid >3 log viral load reduction in monotherapy at oral doses of 3 mg or greater with once-daily dosing in genotype 1a HCV-infected patients. 39 has been shown to be safe and efficacious, with SVR12 rates up to 100% when used in combination with direct-acting antivirals having complementary mechanisms.
|
Antiviral activity against HCV genotype 1a H77 infected in human HuH7 cells assessed as inhibition of viral RNA replication after 3 days by renilla luciferase reporter gene assay in presence of human serum
|
Hepatitis C virus (isolate H77)
|
0.21
nM
|
|
Journal : J. Med. Chem.
Title : Discovery of ledipasvir (GS-5885): a potent, once-daily oral NS5A inhibitor for the treatment of hepatitis C virus infection.
Year : 2014
Volume : 57
Issue : 5
First Page : 2033
Last Page : 2046
Authors : Link JO, Taylor JG, Xu L, Mitchell M, Guo H, Liu H, Kato D, Kirschberg T, Sun J, Squires N, Parrish J, Keller T, Yang ZY, Yang C, Matles M, Wang Y, Wang K, Cheng G, Tian Y, Mogalian E, Mondou E, Cornpropst M, Perry J, Desai MC.
Abstract : A new class of highly potent NS5A inhibitors with an unsymmetric benzimidazole-difluorofluorene-imidazole core and distal [2.2.1]azabicyclic ring system was discovered. Optimization of antiviral potency and pharmacokinetics led to the identification of 39 (ledipasvir, GS-5885). Compound 39 (GT1a replicon EC50 = 31 pM) has an extended plasma half-life of 37-45 h in healthy volunteers and produces a rapid >3 log viral load reduction in monotherapy at oral doses of 3 mg or greater with once-daily dosing in genotype 1a HCV-infected patients. 39 has been shown to be safe and efficacious, with SVR12 rates up to 100% when used in combination with direct-acting antivirals having complementary mechanisms.
|
Antiviral activity against HCV genotype 1b Con1 infected in human HuH7 cells assessed as inhibition of viral RNA replication after 3 days by renilla luciferase reporter gene assay in presence of 10% BSA
|
Hepatitis C virus (isolate Con1)
|
0.027
nM
|
|
Journal : J. Med. Chem.
Title : Discovery of ledipasvir (GS-5885): a potent, once-daily oral NS5A inhibitor for the treatment of hepatitis C virus infection.
Year : 2014
Volume : 57
Issue : 5
First Page : 2033
Last Page : 2046
Authors : Link JO, Taylor JG, Xu L, Mitchell M, Guo H, Liu H, Kato D, Kirschberg T, Sun J, Squires N, Parrish J, Keller T, Yang ZY, Yang C, Matles M, Wang Y, Wang K, Cheng G, Tian Y, Mogalian E, Mondou E, Cornpropst M, Perry J, Desai MC.
Abstract : A new class of highly potent NS5A inhibitors with an unsymmetric benzimidazole-difluorofluorene-imidazole core and distal [2.2.1]azabicyclic ring system was discovered. Optimization of antiviral potency and pharmacokinetics led to the identification of 39 (ledipasvir, GS-5885). Compound 39 (GT1a replicon EC50 = 31 pM) has an extended plasma half-life of 37-45 h in healthy volunteers and produces a rapid >3 log viral load reduction in monotherapy at oral doses of 3 mg or greater with once-daily dosing in genotype 1a HCV-infected patients. 39 has been shown to be safe and efficacious, with SVR12 rates up to 100% when used in combination with direct-acting antivirals having complementary mechanisms.
|
Antiviral activity against HCV genotype 1b Con1 infected in human HuH7 cells assessed as inhibition of viral RNA replication after 3 days by renilla luciferase reporter gene assay
|
Hepatitis C virus (isolate Con1)
|
0.004
nM
|
|
Journal : J. Med. Chem.
Title : Discovery of ledipasvir (GS-5885): a potent, once-daily oral NS5A inhibitor for the treatment of hepatitis C virus infection.
Year : 2014
Volume : 57
Issue : 5
First Page : 2033
Last Page : 2046
Authors : Link JO, Taylor JG, Xu L, Mitchell M, Guo H, Liu H, Kato D, Kirschberg T, Sun J, Squires N, Parrish J, Keller T, Yang ZY, Yang C, Matles M, Wang Y, Wang K, Cheng G, Tian Y, Mogalian E, Mondou E, Cornpropst M, Perry J, Desai MC.
Abstract : A new class of highly potent NS5A inhibitors with an unsymmetric benzimidazole-difluorofluorene-imidazole core and distal [2.2.1]azabicyclic ring system was discovered. Optimization of antiviral potency and pharmacokinetics led to the identification of 39 (ledipasvir, GS-5885). Compound 39 (GT1a replicon EC50 = 31 pM) has an extended plasma half-life of 37-45 h in healthy volunteers and produces a rapid >3 log viral load reduction in monotherapy at oral doses of 3 mg or greater with once-daily dosing in genotype 1a HCV-infected patients. 39 has been shown to be safe and efficacious, with SVR12 rates up to 100% when used in combination with direct-acting antivirals having complementary mechanisms.
|
Antiviral activity against HCV genotype 1a H77 infected in human HuH7 cells assessed as inhibition of viral RNA replication after 3 days by renilla luciferase reporter gene assay
|
Hepatitis C virus (isolate H77)
|
0.031
nM
|
|
Journal : J. Med. Chem.
Title : Discovery of ledipasvir (GS-5885): a potent, once-daily oral NS5A inhibitor for the treatment of hepatitis C virus infection.
Year : 2014
Volume : 57
Issue : 5
First Page : 2033
Last Page : 2046
Authors : Link JO, Taylor JG, Xu L, Mitchell M, Guo H, Liu H, Kato D, Kirschberg T, Sun J, Squires N, Parrish J, Keller T, Yang ZY, Yang C, Matles M, Wang Y, Wang K, Cheng G, Tian Y, Mogalian E, Mondou E, Cornpropst M, Perry J, Desai MC.
Abstract : A new class of highly potent NS5A inhibitors with an unsymmetric benzimidazole-difluorofluorene-imidazole core and distal [2.2.1]azabicyclic ring system was discovered. Optimization of antiviral potency and pharmacokinetics led to the identification of 39 (ledipasvir, GS-5885). Compound 39 (GT1a replicon EC50 = 31 pM) has an extended plasma half-life of 37-45 h in healthy volunteers and produces a rapid >3 log viral load reduction in monotherapy at oral doses of 3 mg or greater with once-daily dosing in genotype 1a HCV-infected patients. 39 has been shown to be safe and efficacious, with SVR12 rates up to 100% when used in combination with direct-acting antivirals having complementary mechanisms.
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging
|
Homo sapiens
|
21.65
%
|
|
Title : Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection
Year : 2020
Authors : Bernhard Ellinger, Denisa Bojkova, Andrea Zaliani, Jindrich Cinatl, Carsten Claussen, Sandra Westhaus, Jeanette Reinshagen, Maria Kuzikov, Markus Wolf, Gerd Geisslinger, Philip Gribbon, Sandra Ciesek
Abstract : To identify possible candidates for progression towards clinical studies against SARS-CoV-2, we screened a well-defined collection of 5632 compounds including 3488 compounds which have undergone clinical investigations (marketed drugs, phases 1 -3, and withdrawn) across 600 indications. Compounds were screened for their inhibition of viral induced cytotoxicity using the human epithelial colorectal adenocarcinoma cell line Caco-2 and a SARS-CoV-2 isolate. The primary screen of 5632 compounds gave 271 hits. A total of 64 compounds with IC50 <20 µM were identified, including 19 compounds with IC50 < 1 µM. Of this confirmed hit population, 90% have not yet been previously reported as active against SARS-CoV-2 in-vitro cell assays. Some 37 of the actives are launched drugs, 19 are in phases 1-3 and 10 pre-clinical. Several inhibitors were associated with modulation of host pathways including kinase signaling P53 activation, ubiquitin pathways and PDE activity modulation, with long chain acyl transferases were effective viral inhibitors.
|
Inhibition of NS5A in HCV genotype 2a JFH-1 by cell based luciferase reporter gene assay
|
Hepatitis C virus subtype 2a
|
21.0
nM
|
|
Journal : J Med Chem
Title : Discovery and Characterization of Potent Pan-Genotypic HCV NS5A Inhibitors Containing Novel Tricyclic Central Core Leading to Clinical Candidate.
Year : 2019
Volume : 62
Issue : 23
First Page : 10563
Last Page : 10582
Authors : Ramdas V, Talwar R, Banerjee M, Joshi AA, Das AK, Walke DS, Borhade P, Dhayagude U, Loriya R, Gote G, Bommakanti A, Sivaram A, Agarwal G, Goswami A, Nigade P, Mehta M, Patil V, Modi D, Kumar H, Mallurwar S, Dash A, Modi F, Kuldharan S, Srivastava P, Singh M, Narasimham L, Gundu J, Sharma S, Kamboj RK, Palle VP.
Abstract : The identification of a novel class of potent pan-genotypic NS5A inhibitors with good pharmacokinetic profile suitable for potential use in treating HCV infections is disclosed here. The present series of compounds are with less complex tricyclic central core, identified through a systematic SAR study carried out on biphenyl moiety. The SAR outcome has confirmed the requirement of near planar and linear conformation of the molecule to achieve the best pan-genotypic activity. In addition, SAR with substituted imidazoles on improvement of antiviral activity is disclosed. The newly identified compounds 12, 16, 19-21 have shown desirable pharmacokinetic profiles with a favorable uptake of compounds in liver and maintained a significant concentration for up to 8 h in the liver. In addition, compounds 20 and 21 have shown superior pan-genotypic anti-HCV activity compared to ledipasvir and daclatasvir. Additional characterization and preliminary safety assessment resulted in the identification of compound 20 as a potential clinical candidate.
|
Inhibition of NS5A in HCV genotype 3a by cell based luciferase reporter gene assay
|
Hepatitis C virus subtype 3a
|
41.0
nM
|
|
Journal : J Med Chem
Title : Discovery and Characterization of Potent Pan-Genotypic HCV NS5A Inhibitors Containing Novel Tricyclic Central Core Leading to Clinical Candidate.
Year : 2019
Volume : 62
Issue : 23
First Page : 10563
Last Page : 10582
Authors : Ramdas V, Talwar R, Banerjee M, Joshi AA, Das AK, Walke DS, Borhade P, Dhayagude U, Loriya R, Gote G, Bommakanti A, Sivaram A, Agarwal G, Goswami A, Nigade P, Mehta M, Patil V, Modi D, Kumar H, Mallurwar S, Dash A, Modi F, Kuldharan S, Srivastava P, Singh M, Narasimham L, Gundu J, Sharma S, Kamboj RK, Palle VP.
Abstract : The identification of a novel class of potent pan-genotypic NS5A inhibitors with good pharmacokinetic profile suitable for potential use in treating HCV infections is disclosed here. The present series of compounds are with less complex tricyclic central core, identified through a systematic SAR study carried out on biphenyl moiety. The SAR outcome has confirmed the requirement of near planar and linear conformation of the molecule to achieve the best pan-genotypic activity. In addition, SAR with substituted imidazoles on improvement of antiviral activity is disclosed. The newly identified compounds 12, 16, 19-21 have shown desirable pharmacokinetic profiles with a favorable uptake of compounds in liver and maintained a significant concentration for up to 8 h in the liver. In addition, compounds 20 and 21 have shown superior pan-genotypic anti-HCV activity compared to ledipasvir and daclatasvir. Additional characterization and preliminary safety assessment resulted in the identification of compound 20 as a potential clinical candidate.
|
Inhibition of NS5A in wild type HCV genotype 1a infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 1a
|
0.031
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A in HCV genotype 6a HK6 infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 6a
|
1.1
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A in HCV genotype 1a H77 infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 1a
|
0.031
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A in HCV genotype 1b Con1 infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 1b
|
0.004
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A in HCV genotype 2a JFH1 infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 2a
|
21.0
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A in HCV genotype 2a J6 infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 2a
|
249.0
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A in HCV genotype 2b MD2b-1 infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 2b
|
530.0
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A in HCV genotype 3a S52 infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 3a
|
168.0
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A in HCV genotype 4a ED43 infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 4a
|
0.39
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A in HCV genotype 5a SA13 infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 5a
|
0.15
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A in HCV genotype 6e D88 infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 6e
|
264.0
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A M28T mutant in HCV genotype 1a infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 1a
|
1.9
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A Q30H mutant in HCV genotype 1a infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 1a
|
5.7
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A Q30R mutant in HCV genotype 1a infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 1a
|
19.6
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A L31M mutant in HCV genotype 1a infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 1a
|
17.0
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A Y93C mutant in HCV genotype 1a infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 1a
|
49.6
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A Q30E mutant in HCV genotype 1a infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 1a
|
169.0
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A Y93H mutant in HCV genotype 1a infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 1a
|
52.0
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A in wild type HCV genotype 1b infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 1b
|
0.004
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A Y93H mutant in HCV genotype 1b infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 1b
|
7.2
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A in HCV wild type genotype 2a infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 2a
|
209.0
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A K44R mutant in HCV genotype 2a infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 2a
|
164.0
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A N62V mutant in HCV genotype 2a infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 2a
|
222.0
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A N62S mutant in HCV genotype 2a infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 2a
|
123.0
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A in wild type HCV genotype 2b MD2b-1 infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 2b
|
865.0
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A in wild type HCV genotype 2b AY232738 infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 2b
|
211.0
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A A30K mutant in HCV genotype 3a infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 3a
|
88.8
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A Y93H mutant in HCV genotype 3a infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 3a
|
88.8
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A R44K mutant in HCV genotype 2b infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 2b
|
943.0
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A P58S mutant in HCV genotype 2b infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 2b
|
292.0
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
Inhibition of NS5A in wild type HCV genotype 3a infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
|
Hepatitis C virus subtype 3a
|
44.8
nM
|
|
Journal : Bioorg Med Chem Lett
Title : Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi<sup>®</sup> and Epclusa<sup>®</sup>.
Year : 2019
Volume : 29
Issue : 16
First Page : 2415
Last Page : 2427
Authors : Link JO, Taylor JG, Trejo-Martin A, Kato D, Katana AA, Krygowski ES, Yang ZY, Zipfel S, Cottell JJ, Bacon EM, Tran CV, Yang CY, Wang Y, Wang KW, Zhao G, Cheng G, Tian Y, Gong R, Lee YJ, Yu M, Gorman E, Mogalian E, Perry JK.
Abstract : Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa<sup>®</sup>, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi<sup>®</sup>, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
-42.05
%
|
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
-32.04
%
|
|
Title : Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen
Year : 2020
Authors : Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani
Abstract : Compound repurposing is an important strategy being pursued in the identification of effective treatment against the SARS-CoV-2 infection and COVID-19 disease. In this regard, SARS-CoV-2 main protease (M-Pro), also termed 3CL-Pro, is an attractive drug target as it plays a central role in viral replication by processing the viral polyprotein into 11 non-structural proteins. We report the results of a screening campaign involving ca 8.7 K compounds containing marketed drugs, clinical and preclinical candidates, and chemicals regarded as safe in humans. We confirmed previously reported inhibitors of 3CL-Pro, but we have also identified 68 compounds with IC50 lower than 1 uM and 127 compounds with IC50 lower than 5 uM. Profiling showed 67% of confirmed hits were selective (> 5 fold) against other Cys- and Ser- proteases (Chymotrypsin and Cathepsin-L) and MERS 3CL-Pro. Selected compounds were also analysed in their binding characteristics.
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
0.27
%
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
0.15
%
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
0.27
%
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
0.15
%
|
|
Title : Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort
Year : 2020
Authors : Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen
Abstract : Worldwide, there are intensive efforts to identify repurposed drugs as potential therapies against SARS-CoV-2 infection and the associated COVID-19 disease. To date, the anti-inflammatory drug dexamethasone and (to a lesser extent) the RNA-polymerase inhibitor remdesivir have been shown to be effective in reducing mortality and patient time to recovery, respectively, in patients. Here, we report the results of a phenotypic screening campaign within an EU-funded project (H2020-EXSCALATE4COV) aimed at extending the repertoire of anti-COVID therapeutics through repurposing of available compounds and highlighting compounds with new mechanisms of action against viral infection. We screened 8702 molecules from different repurposing libraries, to reveal 110 compounds with an anti-cytopathic IC50 < 20 µM. From this group, 18 with a safety index greater than 2 are also marketed drugs, making them suitable for further study as potential therapies against COVID-19. Our result supports the idea that a systematic approach to repurposing is a valid strategy to accelerate the necessary drug discovery process.
|
Inhibition of HCV NS3/4a protease
|
Hepatitis C virus
|
99.0
%
|
|
Journal : Eur J Med Chem
Title : Hepatitis C - New drugs and treatment prospects.
Year : 2019
Volume : 165
First Page : 225
Last Page : 249
Authors : Zając M, Muszalska I, Sobczak A, Dadej A, Tomczak S, Jelińska A.
Abstract : Hepatitis C virus (HCV) affects approx. 3% of the world's population and accounts for ca 300 000 deaths per year. 80% of individuals with HCV develop chronic symptoms which, when untreated, may cause cirrhosis (27%) or hepatocellular carcinoma (25%). The hepatitis C virus is a (+)ssRNA enveloped virus of the family Flaviviridae. Seven major HCV genotypes and their subtypes (a, b) have been identified. In the 1990s, interferons alpha-2 were used in the treatment of HCV and in the next decade HCV therapy was based on pegylated interferon alpha-2 in combination with ribavirin. Since 2011, interferons alpha, DNA and RNA polymerase inhibitors, NS3/4A RNA protease inhibitors, NS5 RNA serine protease inhibitors, NS5B RNA polymerase inhibitors have been approved for clinical use. Monotherapy is avoided in medication due to rapidly developing viral resistance. A total of 113 papers were included comprising original publications and reviews. The paper reviews the molecular targets and chemical structures of drugs used in HCV treatment. Indications and contraindications for anti-HCV drugs are also discussed together with application regimens.
