PMC:7600245 / 36050-37609 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7600245","sourcedb":"PMC","sourceid":"7600245","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7600245","text":"3.4. Danoprevir/Ritonavir\nDanoprevir (Ganovo) is an orally bioavailable 15-membered macrocyclic peptidomimetic antiviral drug (Figure S4). It is an inhibitor of NS3/4A HCV protease, an important processing enzyme complex. It inhibits the protease with an IC50 value of 0.29 nM [112]. It was approved in China in 2018 to treat chronic HCV patients. At higher concentrations, it also appears to inhibit the aspartate protease of HIV. The NS3/4A protease of HCV is claimed to share a certain level of structural and/or functional similarity to the protease(s) of SARS-CoV-2. Thus, HCV protease inhibitors, including danoprevir, have been proposed as potential therapeutics for COVID-19. This has also been supported by computational work which indicated that HCV protease inhibitors have high binding affinity to 3CLpro of SARS-CoV-2 [113] and by in vitro and clinical studies which showed that patients with SARS-CoV or MERS-CoV may benefit from HCV protease inhibitors [88,90,114]. Currently, danoprevir in combination with ritonavir, is being evaluated in two clinical trials (NCT04345276; n = 10) and (with nebulized INF; NCT04291729; n = 11) for the treatment of COVID-19 patients. As mentioned earlier, ritonavir is an antiviral and pharmacokinetic booster that extends the systemic exposure of patients to potential therapeutic concentration of danoprevir. In fact, a recent clinical study results under review has indicated that danoprevir/ritonavir combination alleviated the symptoms in COVID-patients and accelerated their recovery in 4–12 days 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