Human infections with influenza H7 subtypes, such as H7Ng, have raised concerns worldwide. Here, we report a human infection with a novel influenza A（HTN4） virus. A 68 years-old woman with cardiovascular and cholecy...Human infections with influenza H7 subtypes, such as H7Ng, have raised concerns worldwide. Here, we report a human infection with a novel influenza A（HTN4） virus. A 68 years-old woman with cardiovascular and cholecystic comorbidities developed rapidly progressed pneumonia with influenza-like-illness as initial symptom, recovered after 23 days-hospitalization including 8 days in ICLI. Laboratory indicators for liver and blood coagulation dysfunction were observed. Oseltamivir phosphate, glucocorticoids and antibiotics were jointly implemented, with nasal catheterization of oxygen inhalation for this patient. We obtained the medical records and collected serial respiratory and blood specimens from her. We col- lected throat, cloacal and/or feces samples of poultry and wild birds from the patient＇s backyard, neigh- borhood, local live poultry markets （LPMs） and the nearest lake. All close contacts of the patient were followed up and sampled with throat swabs and sera. Influenza viruses and other respiratory pathogens were tested by real-time RT-PCR, viral culturing and/or sequencing for human respiratory and bird sam- ples. Micro-neutralizing assay was performed for sera. A novel reassortant wild bird-origin H7N4 virus is identified from the patient and her backyard poultry （chickens and ducks） by sequencing, which is dis- tinct from previously-reported avian H7N4 and H7N9 viruses. At least four folds increase of neutralizing antibodies to H7N4 was detected in her convalescent sera. No samples from close contacts, wild birds or other poultry were tested positive for H7N4 by real-time RT-PCR.展开更多
The global spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)requires an urgent need to find effective therapeutics for the treatment of coronavirus disease 2019(COVID-19).In this study,we developed...The global spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)requires an urgent need to find effective therapeutics for the treatment of coronavirus disease 2019(COVID-19).In this study,we developed an integrative drug repositioning framework,which fully takes advantage of machine learning and statistical analysis approaches to systematically integrate and mine large-scale knowledge graph,literature and transcriptome data to discover the potential drug candidates against SARS-CoV-2.Our in silico screening followed by wet-lab validation indicated that a poly-ADP-ribose polymerase 1(PARP1)inhibitor,CVL218,currently in Phase I clinical trial,may be repurposed to treat COVID-19.Our in vitro assays revealed that CVL218 can exhibit effective inhibitory activity against SARS-CoV-2 replication without obvious cytopathic effect.In addition,we showed that CVL218 can interact with the nucleocapsid(N)protein of SARS-CoV-2 and is able to suppress the LPS-induced production of several inflammatory cytokines that are highly relevant to the prevention of immunopathology induced by SARS-CoV-2 infection.展开更多
基金supported by National Science and Technology Major Project of China (2015ZX09101044)Science & Technology Demonstration Project for Emerging Infectious Diseases Control and Prevention of Jiangsu Province, China (BE2015714 & BE2017749)Key Medical Discipline of Jiangsu Science & Technology Project of China (epidemiology,ZDXKA2016008)
文摘Human infections with influenza H7 subtypes, such as H7Ng, have raised concerns worldwide. Here, we report a human infection with a novel influenza A（HTN4） virus. A 68 years-old woman with cardiovascular and cholecystic comorbidities developed rapidly progressed pneumonia with influenza-like-illness as initial symptom, recovered after 23 days-hospitalization including 8 days in ICLI. Laboratory indicators for liver and blood coagulation dysfunction were observed. Oseltamivir phosphate, glucocorticoids and antibiotics were jointly implemented, with nasal catheterization of oxygen inhalation for this patient. We obtained the medical records and collected serial respiratory and blood specimens from her. We col- lected throat, cloacal and/or feces samples of poultry and wild birds from the patient＇s backyard, neigh- borhood, local live poultry markets （LPMs） and the nearest lake. All close contacts of the patient were followed up and sampled with throat swabs and sera. Influenza viruses and other respiratory pathogens were tested by real-time RT-PCR, viral culturing and/or sequencing for human respiratory and bird sam- ples. Micro-neutralizing assay was performed for sera. A novel reassortant wild bird-origin H7N4 virus is identified from the patient and her backyard poultry （chickens and ducks） by sequencing, which is dis- tinct from previously-reported avian H7N4 and H7N9 viruses. At least four folds increase of neutralizing antibodies to H7N4 was detected in her convalescent sera. No samples from close contacts, wild birds or other poultry were tested positive for H7N4 by real-time RT-PCR.
基金This work was supported in part by the National Natural Science Foundation of China(61872216,81630103,31900862,31725014)Jiangsu Provincial Emergency Project on Prevention and Control of COVID-19 Epidemic(BE2020601)+2 种基金the Nation Science and Technology Major Projects for Major New Drugs Innovation and Development(2018ZX09711003-004-002,2019ZX09301010)Pudong New Area Science and Technology Development Foundation(PKX2019-S08)the Turing Al Institute of Nanjing,and the Zhongguancun Haihua Institute for Frontier Information Technology.
文摘The global spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)requires an urgent need to find effective therapeutics for the treatment of coronavirus disease 2019(COVID-19).In this study,we developed an integrative drug repositioning framework,which fully takes advantage of machine learning and statistical analysis approaches to systematically integrate and mine large-scale knowledge graph,literature and transcriptome data to discover the potential drug candidates against SARS-CoV-2.Our in silico screening followed by wet-lab validation indicated that a poly-ADP-ribose polymerase 1(PARP1)inhibitor,CVL218,currently in Phase I clinical trial,may be repurposed to treat COVID-19.Our in vitro assays revealed that CVL218 can exhibit effective inhibitory activity against SARS-CoV-2 replication without obvious cytopathic effect.In addition,we showed that CVL218 can interact with the nucleocapsid(N)protein of SARS-CoV-2 and is able to suppress the LPS-induced production of several inflammatory cytokines that are highly relevant to the prevention of immunopathology induced by SARS-CoV-2 infection.
