Some medically important viruses-including retroviruses, flaviviruses, coronaviruses, and herpesviruses-code for a protease, which is indispensable for viral maturation and pathogenesis. Viral protease inhibitors have become an important class of antiviral drugs. Development of the first-in-class viral protease inhibitor saquinavir, which targets HIV protease, started a new era in the treatment of chronic viral diseases. Combining several drugs that target different steps of the viral life cycle enables use of lower doses of individual drugs (and thereby reduction of potential side effects, which frequently occur during long term therapy) and reduces drug-resistance development. Currently, several HIV and HCV protease inhibitors are routinely used in clinical practice. In addition, a drug including an inhibitor of SARS-CoV-2 main protease, nirmatrelvir (co-administered with a pharmacokinetic booster ritonavir as Paxlovid®), was recently authorized for emergency use. This review summarizes the basic features of the proteases of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and SARS-CoV-2 and discusses the properties of their inhibitors in clinical use, as well as development of compounds in the pipeline.

• MeSH
• antivirové látky farmakologie   terapeutické užití   MeSH
• COVID-19 * MeSH
• HIV infekce * farmakoterapie   MeSH
• lidé MeSH
• SARS-CoV-2 MeSH
• virové proteasy MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antivirové látky MeSH
• nirmatrelvir and ritonavir drug combination MeSH Prohlížeč
• virové proteasy MeSH

INTRODUCTION: Some direct-acting antiviral regimens for hepatitis C virus (HCV) infection pose safety or efficacy concerns if coadministered with drugs containing ethinyl estradiol. The present analysis was conducted to examine the impact of concomitant oral contraceptive pills (OCP) or hormone replacement therapy (HRT) during treatment with elbasvir (EBR)/grazoprevir (GZR) in women with HCV genotype (GT)1 or GT4 infection. METHODS: This is a post hoc, integrated retrospective analysis of female participants with HCV GT1 or GT4 infection who received EBR 50 mg/GZR 100 mg once daily for 12 weeks in phase 2/3 clinical trials. The primary end point was sustained virologic response at 12 weeks after therapy completion (SVR12). For this analysis, participants were stratified according to whether they received OCP or HRT during the original treatment study. RESULTS: A total of 1,022 women with HCV GT1 or GT4 infection were included (receiving OCP/HRT, n=81; not receiving OCP/HRT, n=941). Most participants receiving OCP/HRT were treatment-naive (79%), noncirrhotic (91.4%), and aged >35 years (71.6%). SVR12 rates were similar in women receiving OCP/HRT and those not receiving OCP/HRT (95.1% vs 96.3%). SVR12 rates remained high across all subgroups within the population receiving OCP/HRT: SVR12 rates were 94.6%, 100%, and 100% in participants with GT1a, GT1b, and GT4 infection, and all women aged 18-35 years achieved SVR (21/21). Treatment-related adverse events occurred in 40.7% (33/81) and 30.1% (283/941) of women receiving and those not receiving OCP/HRT, respectively. CONCLUSION: The efficacy and safety of EBR/GZR administered for 12 weeks was similar in women receiving OCP/HRT and those not on OCP/HRT. These data indicate that EBR/GZR can be safely used for the treatment of HCV GT1 or GT4 infection in women receiving concomitant OCP/HRT.

• Klíčová slova
• NS3/4A protease inhibitor, NS5A inhibitor, clinical trial, ethinyl estradiol, levonorgestrel,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Genotype 1b (GT1b) is the most common subtype of the hepatitis C virus (HCV). We present an integrated analysis of 1070 participants with HCV GT1b infection from 30 countries who received elbasvir/grazoprevir for 12 weeks. METHODS: This is a retrospective analysis of data from participants with chronic HCV GT1b infection enrolled in 11 phase II/III clinical trials. All participants received elbasvir 50 mg plus grazoprevir 100 mg once daily for 12 weeks. The primary end point of all studies was sustained virologic response 12 weeks after completion of therapy (SVR12, HCV RNA < 15 IU/ml). RESULTS: SVR12 was 97.2% (1040/1070). Of the 30 participants who failed to attain SVR12, 15 relapsed and 15 had nonvirologic failure. Among participant subgroups, SVR12 was high in those with compensated cirrhosis (188/189, 99.5%), HIV co-infection (51/54, 94.4%), and baseline viral load > 800,000 IU/ml (705/728, 96.8%). Resistance-associated substitutions (RASs) at NS5A positions 28, 30, 31, or 93 were present in 21.6% of participants at baseline. SVR12 was 99.6% (820/823) in participants without baseline NS5A RASs and 94.7% (215/227) in those with baseline NS5A RASs. Serious adverse events occurred in 3.2% (34/1070) of participants, nine of which occurred after study medication was completed. CONCLUSIONS: Elbasvir/grazoprevir for 12 weeks represents an effective treatment option for participants with HCV GT1b infection. SVR12 was high in all participant subgroups, including those with compensated cirrhosis, HIV co-infection, and high baseline viral load. CLINICALTRIALS. GOV IDENTIFIERS: The trials discussed in this paper were registered with Clinicaltrial.gov as the following: NCT02092350 (C-SURFER), NCT02105662 (C-EDGE Co-Infection), NCT02105467 (C-EDGE treatment-naive), NCT02105701 (C-EDGE treatment-experienced), NCT01717326 (C-WORTHy), NCT02251990 (C-CORAL), NCT02105688 (C-EDGE COSTAR), NCT02252016 (C-EDGE IBLD), NCT02115321 (C-SALT), NCT02203149 (Japan phase 2/3 study), NCT02358044 (C-EDGE Head-2-Head).

• Klíčová slova
• Hepatitis, Retrospective, Therapy,
• MeSH
• amidy MeSH
• antivirové látky škodlivé účinky   terapeutické užití   MeSH
• benzofurany škodlivé účinky   terapeutické užití   MeSH
• chinoxaliny škodlivé účinky   terapeutické užití   MeSH
• chronická hepatitida C komplikace   farmakoterapie   virologie   MeSH
• cyklopropany MeSH
• dospělí MeSH
• genotyp MeSH
• Hepacivirus genetika   MeSH
• HIV infekce komplikace   MeSH
• imidazoly škodlivé účinky   terapeutické užití   MeSH
• jaterní cirhóza patofyziologie   virologie   MeSH
• karbamáty MeSH
• klinické zkoušky, fáze II jako téma MeSH
• klinické zkoušky, fáze III jako téma MeSH
• koinfekce komplikace   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• retrospektivní studie MeSH
• senioři MeSH
• setrvalá virologická odpověď MeSH
• sulfonamidy MeSH
• virová léková rezistence genetika   MeSH
• virová nálož MeSH
• virové nestrukturální proteiny genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• amidy MeSH
• antivirové látky MeSH
• benzofurany MeSH
• chinoxaliny MeSH
• cyklopropany MeSH
• elbasvir MeSH Prohlížeč
• grazoprevir MeSH Prohlížeč
• imidazoly MeSH
• karbamáty MeSH
• NS-5 protein, hepatitis C virus MeSH Prohlížeč
• sulfonamidy MeSH
• virové nestrukturální proteiny MeSH