Azvudine(FNC)is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase(RdRp).Recently,we discovered FNC an agent against SARS-CoV-2,and have taken it into Phase III trial for COVID-19 patients.FNC monoph...Azvudine(FNC)is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase(RdRp).Recently,we discovered FNC an agent against SARS-CoV-2,and have taken it into Phase III trial for COVID-19 patients.FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC_(50) between 1.2 and 4.3 μM,depending on viruses or cells,and selective index(SI)in 15-83 range.Oral administration of FNC in rats revealed a substantial thymus-homing feature,with FNC triphosphate(the active form)concentrated in the thymus and peripheral blood mononuclear cells(PBMC).Treating SARS-CoV-2 infected rhesus macaques with FNC(0.07 mg/kg, qd,orally)reduced viral load,recuperated the thymus,improved lymphocyte profiles,alleviated in flammation and orga n damage,and lessened grou nd・glass opacities in chest X-ray.Sin gle-cell seque ncing suggested the promotion of thymus function by FNC.A randomized,single-arm clinical trial of FNC on compassionate use(n=31)showed that oral FNC(5 mg,qd)cured all COVID-19 patients,with 100%viral ribonucleic acid negative conversion in 3.29±2.22 days(range:1-9 days)and 100%hospital discharge rate in 9.00±4.93 days(range:2-25 days).The side-effect of FNC is minor and transient dizziness and nausea in 16.12%(5/31)patients.Thus,FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus,followed by promoted immunity.展开更多
基金This work was supported by the CAMS Innovation Fund for Medical Sciences(No.2020-I2M-1-003,2020-I2M-2-010,2020HY320001,China)The Drug Innovation Major Project(No.2018ZX09711001-003-002,China)+2 种基金National Natural Science Foundation(No.81621064,China)National key R&D project(No.2019YFC170890,China)CAMS Innovation Fund for Medical Sciences(No.2021-1-I2M-009,2021-1-I2M-030).
文摘Azvudine(FNC)is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase(RdRp).Recently,we discovered FNC an agent against SARS-CoV-2,and have taken it into Phase III trial for COVID-19 patients.FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC_(50) between 1.2 and 4.3 μM,depending on viruses or cells,and selective index(SI)in 15-83 range.Oral administration of FNC in rats revealed a substantial thymus-homing feature,with FNC triphosphate(the active form)concentrated in the thymus and peripheral blood mononuclear cells(PBMC).Treating SARS-CoV-2 infected rhesus macaques with FNC(0.07 mg/kg, qd,orally)reduced viral load,recuperated the thymus,improved lymphocyte profiles,alleviated in flammation and orga n damage,and lessened grou nd・glass opacities in chest X-ray.Sin gle-cell seque ncing suggested the promotion of thymus function by FNC.A randomized,single-arm clinical trial of FNC on compassionate use(n=31)showed that oral FNC(5 mg,qd)cured all COVID-19 patients,with 100%viral ribonucleic acid negative conversion in 3.29±2.22 days(range:1-9 days)and 100%hospital discharge rate in 9.00±4.93 days(range:2-25 days).The side-effect of FNC is minor and transient dizziness and nausea in 16.12%(5/31)patients.Thus,FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus,followed by promoted immunity.
