Catatonia is a psychomotor syndrome that can occur in a broad spectrum of brain disorders,including schizophrenia.Current findings suggest that the neurobiological process underlying catatonia symptoms in schizophreni...Catatonia is a psychomotor syndrome that can occur in a broad spectrum of brain disorders,including schizophrenia.Current findings suggest that the neurobiological process underlying catatonia symptoms in schizophrenia is poorly understood.However,emerging neuroimaging studies in catatonia patients have indicated that a disruption in anatomical connectivity of the cortico-striatal-cerebellar system is part of the neurobiology of catatonia,which could serve as a target of neurostimulation such as electroconvulsive therapy and repetitive transcranial magnetic stimulation.展开更多
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supported by the grant support of Fourth Military Medical University and National Natural Science Foundation of China (82271949)supported by Shanghai Sailing Pr ogr am (21YF1402400).
文摘Catatonia is a psychomotor syndrome that can occur in a broad spectrum of brain disorders,including schizophrenia.Current findings suggest that the neurobiological process underlying catatonia symptoms in schizophrenia is poorly understood.However,emerging neuroimaging studies in catatonia patients have indicated that a disruption in anatomical connectivity of the cortico-striatal-cerebellar system is part of the neurobiology of catatonia,which could serve as a target of neurostimulation such as electroconvulsive therapy and repetitive transcranial magnetic stimulation.
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.
