<p>Danoprevir for the Treatment of Hepatitis C Virus Infection: Design, Development, and Place in Therapy</p>

Abstract

On June 8, 2018, an NS3/4A protease inhibitor called danoprevir was approved in China to treat the infections of HCV genotype (GT) 1b – the most common HCV genotype worldwide. Based on phase 2 and 3 clinical trials, the 12-week regimen of ritonavir-boosted danoprevir (danoprevir/r) plus peginterferon alpha-2a and ribavirin offered 97.1% (200/206) of sustained virologic response at post-treatment week 12 (SVR12) in treatment-naïve non-cirrhotic patients infected with HCV genotype 1b. Adverse events such as anemia, fatigue, fever, and headache were associated with the inclusion of peginterferon alpha-2a and ribavirin in the danoprevir-based regimen. Moreover, drug resistance to danoprevir could be traced to amino acid substitutions (Q80K/R, R155K, D168A/E/H/N/T/V) near the drug-binding pocket of HCV NS3 protease. Despite its approval, the clinical use of danoprevir is currently limited to its combination with peginterferon alpha-2a and ribavirin, thereby driving its development towards interferon-free, ribavirin-free regimens with improved tolerability and adherence. In the foreseeable future, pan-genotypic direct-acting antivirals with better clinical efficacy and less adverse events will be available to treat HCV infections worldwide.

Genetic Diversity of SARS-CoV-2 over a One-Year Period of the COVID-19 Pandemic: A Global Perspective

“…Genetic variants that promote viral fitness and escape may exert a potential impact on current diagnostic tests, vaccines, antiviral strategies, and immune responses [23,40,50]. Close monitoring of key viral variants is critical for the development and optimization of vaccines and antiviral therapies, according to previous experience from the management of viral infections such as influenza virus, respiratory syncytial virus, and human immunodeficiency virus [51][52][53][54][55][56][57].…”

Drug Discovery of Nucleos(t)ide Antiviral Agents: Dedicated to Prof. Dr. Erik De Clercq on Occasion of His 80th Birthday

“…As of February 2021, at least six adenosine nucleos(t)ide analogues have been officially approved for clinical use, including (i) tenofovir disoproxil fumarate (Viread ® ) for HIV and HBV treatment, (ii) tenofovir alafenamide (Vemlidy ® ) for HIV and HBV treatment, (iii) adefovir dipivoxil (Hepsera ® ) for HBV treatment, (vi) abacavir (Ziagen ® ) for HIV treatment, (v) vidarabine (Vira-A ® , which is now discontinued) for HSV and VZV treatment, and (vi) remdesivir (Veklury ® ) for COVID-19 treatment ( Figure 1 ). This section focuses on the former three adenosine analogues contributed by Prof. Erik De Clercq, while the other drugs have been reviewed in previous studies [ 3 , 22 , 23 , 24 , 25 ].…”

Life-long passion for antiviral research and drug development: 80th birthday of Prof. Dr. Erik De Clercq

“…As the students of Prof. Erik De Clercq, we, fortunately, undertook his COVID-19 courses and followed his generous instructions on many studies [1] , [2] , [36] , [104] , [105] , [106] , [107] , [108] , [109] , [110] , [111] . During the COVID-19 pandemic, our professor and our team quickly responded to the emerging infectious disease.…”