First clinical study using HCV protease inhibitor danoprevir to treat COVID-19 patients

Medicine (Baltimore). 2020 Nov 25;99(48):e23357. doi: 10.1097/MD.0000000000023357.

Abstract

Introduction: As coronavirus disease 2019 (COVID-19) outbreak globally, repurposing approved drugs is emerging as important therapeutic options. Danoprevir boosted by ritonavir (Ganovo) is a potent hepatitis C virus (HCV) protease (NS3/4A) inhibitor, which was approved and marketed in China since 2018 to treat chronic hepatitis C patients.

Methods: This is an open-label, single arm study evaluating the effects of danoprevir boosted by ritonavir on treatment naïve and experienced COVID-19 patients for the first time. Patients received danoprevir boosted by ritonavir (100 mg/100 mg, twice per day). The primary endpoint was the rate of composite adverse outcomes and efficacy was also evaluated.

Results: The data showed that danoprevir boosted by ritonavir is safe and well tolerated in all patients. No patient had composite adverse outcomes during this study. After initiation of danoprevir/ritonavir treatment, the first negative reverse real-time PCR (RT-PCR) test occurred at a median of 2 days, ranging from 1 to 8 days, and the obvious absorption in CT scans occurred at a median 3 days, ranging from 2 to 4 days. After 4 to 12-day treatment of danoprevir boosted by ritonavir, all enrolled 11 patients were discharged from the hospital.

Conclusion: Our findings suggest that repurposing danoprevir for COVID-19 is a promising therapeutic option.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • COVID-19 / diagnostic imaging
  • COVID-19 Drug Treatment*
  • Cyclopropanes / administration & dosage
  • Cyclopropanes / adverse effects
  • Cyclopropanes / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Isoindoles / administration & dosage
  • Isoindoles / adverse effects
  • Isoindoles / therapeutic use*
  • Lactams, Macrocyclic / administration & dosage
  • Lactams, Macrocyclic / adverse effects
  • Lactams, Macrocyclic / therapeutic use*
  • Male
  • Middle Aged
  • Pandemics
  • Proline / administration & dosage
  • Proline / adverse effects
  • Proline / analogs & derivatives*
  • Proline / therapeutic use
  • Real-Time Polymerase Chain Reaction
  • Ritonavir / administration & dosage
  • Ritonavir / adverse effects
  • Ritonavir / therapeutic use*
  • SARS-CoV-2
  • Sulfonamides / administration & dosage
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use*
  • Tomography, X-Ray Computed
  • Young Adult

Substances

  • Antiviral Agents
  • Cyclopropanes
  • Isoindoles
  • Lactams, Macrocyclic
  • Sulfonamides
  • danoprevir
  • Proline
  • Ritonavir