Dear Editor To date,tens of millions of people have been infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),causing the outbreak of the respiratory disease named the coronavirus disease 2019(COV...Dear Editor To date,tens of millions of people have been infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),causing the outbreak of the respiratory disease named the coronavirus disease 2019(COVID-19).As a newly emerged member of the coronavirus family,SARS-CoV-2 is an enveloped positive-strand RNA virus,which has probably the largest genome(approximately 30 kb)among all RNA viruses.The nucleocapsid(N)protein of SARS-CoV-2 is mainly responsible for recognizing and wrapping viral RNA into helically symmetric structures(Malik,2020).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This work was supported in part by the National Natural Science Foundation of China(61872216 and 81630103 to JZ,31900862 to DZ,31871443 to PL)the National Key R&D Program(2019YFA0508403 to PL,2020YFA0803300 to HL)the Turing Al Institute of Nanjing and the Zhongguancun Haihua Institute for Frontier Information Technology.
文摘Dear Editor To date,tens of millions of people have been infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),causing the outbreak of the respiratory disease named the coronavirus disease 2019(COVID-19).As a newly emerged member of the coronavirus family,SARS-CoV-2 is an enveloped positive-strand RNA virus,which has probably the largest genome(approximately 30 kb)among all RNA viruses.The nucleocapsid(N)protein of SARS-CoV-2 is mainly responsible for recognizing and wrapping viral RNA into helically symmetric structures(Malik,2020).
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.
