scholarly journals First Clinical Study Using HCV Protease Inhibitor Danoprevir to Treat Naïve and Experienced COVID-19 Patients

2020 ◽  
Author(s):  
Hongyi Chen ◽  
Zhicheng Zhang ◽  
Li Wang ◽  
Zhihua Huang ◽  
Fanghua Gong ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Clinical Study ◽  
Protease Inhibitor ◽  
Day Treatment ◽  
Therapeutic Option ◽  
Small Sample ◽  
Hiv Protease ◽  
Therapeutic Effects ◽  
Treatment Naïve ◽  
Hcv Protease

AbstractAs coronavirus disease 2019 (COVID-19) outbreak, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), started in China in January, 2020, repurposing approved drugs is emerging as important therapeutic options. We reported here the first clinical study using hepatitis C virus (HCV) protease inhibitor, danoprevir, to treat COVID-19 patients. Danoprevir (Ganovo®) is a potent HCV protease (NS3/4A) inhibitor (IC50 = 0.29 nM), which was approved and marketed in China since 2018 to treat chronic hepatitis C patients. Ritonavir is a CYP3A4 inhibitor to enhance plasma concentration of danoprevir while it also acts as a human immunodeficiency virus (HIV) protease inhibitor at high doses. The chymotrypsin-like protease of SARS-CoV-2 shares structure similarity with HCV and HIV proteases. In the current clinical study (NCT04291729) conducted at the Nineth Hospital of Nanchang, we evaluated therapeutic effects of danoprevir, boosted by ritonavir, on treatment naïve and experienced COVID-19 patients. The data from this small-sample clinical study showed that danoprevir boosted by ritonavir is safe and well tolerated in all patients. After 4 to 12-day treatment of danoprevir boosted by ritonavir, all eleven patients enrolled, two naïve and nine experienced, were discharged from the hospital as they met all four conditions as follows: (1) normal body temperature for at least 3 days; (2) significantly improved respiratory symptoms; (3) lung imaging shows obvious absorption and recovery of acute exudative lesion; and (4) two consecutive RT-PCR negative tests of SARS-CoV-2 nucleotide acid (respiratory track sampling with interval at least one day). Our findings suggest that repurposing danoprevir for COVID-19 is a promising therapeutic option.

scholarly journals Baseline Hepatitis C Virus (HCV) NS3 Polymorphisms and Their Impact on Treatment Response in Clinical Studies of the HCV NS3 Protease Inhibitor Faldaprevir

2013 ◽  
Vol 58 (2) ◽  
pp. 698-705 ◽  
Author(s):  
Kristi L. Berger ◽  
Ibtissem Triki ◽  
Mireille Cartier ◽  
Martin Marquis ◽  
Marie-Josée Massariol ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Amino Acid ◽  
Protease Inhibitor ◽  
Clinical Studies ◽  
Phase 2 ◽  
Genotype 1A ◽  
Treatment Naïve ◽  
Hcv Protease

ABSTRACTA challenge to the treatment of chronic hepatitis C with direct-acting antivirals is the emergence of drug-resistant hepatitis C virus (HCV) variants. HCV with preexisting polymorphisms that are associated with resistance to NS3/4A protease inhibitors have been detected in patients with chronic hepatitis C. We performed a comprehensive pooled analysis from phase 1b and phase 2 clinical studies of the HCV protease inhibitor faldaprevir to assess the population frequency of baseline protease inhibitor resistance-associated NS3 polymorphisms and their impact on response to faldaprevir treatment. A total of 980 baseline NS3 sequences were obtained (543 genotype 1b and 437 genotype 1a sequences). Substitutions associated with faldaprevir resistance (at amino acid positions 155 and 168) were rare (<1% of sequences) and did not compromise treatment response: in a phase 2 study in treatment-naive patients, six patients had faldaprevir resistance-associated polymorphisms at baseline, of whom five completed faldaprevir-based treatment and all five achieved a sustained virologic response 24 weeks after the end of treatment (SVR24). Among 13 clinically relevant amino acid positions associated with HCV protease resistance, the greatest heterogeneity was seen at NS3 codons 132 and 170 in genotype 1b, and the most common baseline substitution in genotype 1a was Q80K (99/437 [23%]). The presence of the Q80K variant did not reduce response rates to faldaprevir-based treatment. Across the three phase 2 studies, there was no significant difference in SVR24 rates between patients with genotype 1a Q80K HCV and those without Q80K HCV, whether treatment experienced (17% compared to 26%;P= 0.47) or treatment naive (62% compared to 66%;P= 0.72).

scholarly journals Ribavirin Antagonizes the In Vitro Anti-Hepatitis C Virus Activity of 2′-C-Methylcytidine, the Active Component of Valopicitabine

2006 ◽  
Vol 50 (10) ◽  
pp. 3444-3446 ◽  
Author(s):  
Lotte Coelmont ◽  
Jan Paeshuyse ◽  
Marc P. Windisch ◽  
Erik De Clercq ◽  
Ralf Bartenschlager ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity ◽  
Protease Inhibitor ◽  
Nucleoside Analogue ◽  
Active Component ◽  
Pyrimidine Nucleoside ◽  
Virus Activity ◽  
Hcv Protease

ABSTRACT Ribavirin antagonizes the in vitro anti-hepatitis C virus (HCV) activity of the pyrimidine nucleoside analogue 2′-C-methylcytidine, the active component of the experimental anti-HCV drug valopicitabine. In contrast, the combination of ribavirin with either the purine nucleoside analogue 2′-C-methyladenosine or the HCV protease inhibitor VX-950 resulted in an additive antiviral activity. These findings may have implications when planning clinical studies with valopicitabine.

Resistance mutations are rare among protease inhibitor treatment-naive hepatitis C genotype 1 patients with or without HIV coinfection

2014 ◽  
Vol 20 (3) ◽  
pp. 281-287 ◽  
Author(s):  
Gaspar Lisboa-Neto ◽  
Caroline F Noble ◽  
João Renato R Pinho ◽  
Fernanda M Malta ◽  
Michele S Gomes-Gouvêa ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Protease Inhibitor ◽  
Genotype 1 ◽  
Resistance Mutations ◽  
Hiv Coinfection ◽  
Treatment Naïve ◽  
Inhibitor Treatment
Sign in / Sign up

Export Citation Format

Share Document