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MeSH Disease

Human Phenotype

Transmission

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Seroprevalence
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    First Clinical Study Using HCV Protease Inhibitor Danoprevir to Treat Naive and Experienced COVID-19 Patients

    Authors: Hongyi Chen; Zhicheng Zhang; Li Wang; Zhihua Huang; Fanghua Gong; Xiaodong Li; Yahong Chen; Jinzi J. WU

    doi:10.1101/2020.03.22.20034041 Date: 2020-03-24 Source: medRxiv

    As coronavirus disease MESHD 2019 (COVID-19) outbreak, caused by the severe acute respiratory syndrome MESHD 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 MESHD hepatitis HP 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 MESHD chronic hepatitis HP patients. Ritonavir is a CYP3A4 inhibitor to enhance plasma SERO concentration of danoprevir while it also acts as a human immunodeficiency HP 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 naive 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 naive 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.

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MeSH Disease
Human Phenotype
Transmission
Seroprevalence


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