An acute respiratory disease,caused by a novel coronavirus(SARS-CoV-2,previously known as 2019-nCoV),the coronavirus disease 2019(COVID-19)has spread throughout China and received worldwide attention.On 30 January 202...An acute respiratory disease,caused by a novel coronavirus(SARS-CoV-2,previously known as 2019-nCoV),the coronavirus disease 2019(COVID-19)has spread throughout China and received worldwide attention.On 30 January 2020,World Health Organization(WHO)officially declared the COVID-19 epidemic as a public health emergency of international concern.The emergence of SARS-CoV-2,since the severe acute respiratory syndrome coronavirus(SARSCoV)in 2002 and Middle East respiratory syndrome coronavirus(MERS-CoV)in 2012,marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the twenty-first century.As of 1 March 2020,a total of 87,137 confirmed cases globally,79,968 confirmed in China and 7169 outside of China,with 2977 deaths(3.4%)had been reported by WHO.Meanwhile,several independent research groups have identified that SARS-CoV-2 belongs toβ-coronavirus,with highly identical genome to bat coronavirus,pointing to bat as the natural host.The novel coronavirus uses the same receptor,angiotensin-converting enzyme 2(ACE2)as that for SARS-CoV,and mainly spreads through the respiratory tract.Importantly,increasingly evidence showed sustained human-tohuman transmission,along with many exported cases across the globe.The clinical symptoms of COVID-19 patients include fever,cough,fatigue and a small population of patients appeared gastrointestinal infection symptoms.The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes,which may be associated with acute respiratory distress syndrome(ARDS)and cytokine storm.Currently,there are few specific antiviral strategies,but several potent candidates of antivirals and repurposed drugs are under urgent investigation.In this review,we summarized the latest research progress of the epidemiology,pathogenesis,and clinical characteristics of COVID-19,and discussed the current treatment and scientific advancements to combat the epidemic novel coronavirus.展开更多
SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths.There are currently no registered therapies for treating coronavirus infections.Because of time consuming process of new drug dev...SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths.There are currently no registered therapies for treating coronavirus infections.Because of time consuming process of new drug development,drug repositioning may be the only solution to the epidemic of sudden infectious diseases.We systematically analyzed all the proteins encoded by SARS-CoV-2 genes,compared them with proteins from other coronavirnses,predicted their structures,and built 19 structures that could be done by homology modeling.By performing target-based virtual ligand screening,a total of21 targets(including two human targets)were screened against compound libraries including ZINC drug database and our own database of natural products.Structure and screening results of important targets such as 3-chymotrypsin-like protease(3 CLpro),Spike,RNA-dependent RNA polymerase(RdRp),and papain like protease(PLpro)were discussed in detail.In addition,a database of 78 commonly used antiviral drugs including those currently on the market and undergoing clinical trials for SARS-CoV-2 was constructed.Possible targets of these compounds and potential drugs acting on a certain target were predicted.This study will provide new lead compounds and targets for further in vitro and in vivo studies of SARS-CoV-2,new insights for those drugs currently ongoing clinical studies,and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections.展开更多
基金by the National Natural Science Foundation of China(81870019)Guangdong Provincial Natural Science Foundation(2018A030313554)+2 种基金National Key R&D Program of China(2018YFC0910601)the National Medical Research Council,Singapore(NMRC/CIRG/1458/2016)a recipient of fellowship support from European Allergy and Clinical Immunology(EAACI)Research Fellowship 2019。
文摘An acute respiratory disease,caused by a novel coronavirus(SARS-CoV-2,previously known as 2019-nCoV),the coronavirus disease 2019(COVID-19)has spread throughout China and received worldwide attention.On 30 January 2020,World Health Organization(WHO)officially declared the COVID-19 epidemic as a public health emergency of international concern.The emergence of SARS-CoV-2,since the severe acute respiratory syndrome coronavirus(SARSCoV)in 2002 and Middle East respiratory syndrome coronavirus(MERS-CoV)in 2012,marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the twenty-first century.As of 1 March 2020,a total of 87,137 confirmed cases globally,79,968 confirmed in China and 7169 outside of China,with 2977 deaths(3.4%)had been reported by WHO.Meanwhile,several independent research groups have identified that SARS-CoV-2 belongs toβ-coronavirus,with highly identical genome to bat coronavirus,pointing to bat as the natural host.The novel coronavirus uses the same receptor,angiotensin-converting enzyme 2(ACE2)as that for SARS-CoV,and mainly spreads through the respiratory tract.Importantly,increasingly evidence showed sustained human-tohuman transmission,along with many exported cases across the globe.The clinical symptoms of COVID-19 patients include fever,cough,fatigue and a small population of patients appeared gastrointestinal infection symptoms.The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes,which may be associated with acute respiratory distress syndrome(ARDS)and cytokine storm.Currently,there are few specific antiviral strategies,but several potent candidates of antivirals and repurposed drugs are under urgent investigation.In this review,we summarized the latest research progress of the epidemiology,pathogenesis,and clinical characteristics of COVID-19,and discussed the current treatment and scientific advancements to combat the epidemic novel coronavirus.
基金support from National Mega-project for Innovative Drugs(grant number 2019ZX09721001-004-007,China)National Natural Science Foundation of China(NSFC,grant numbers U1803122,81773637,81773594,and U1703111)the Fundamental Research Fund for the Central Universities(HUST COVID-19 Rapid Response Call,No.2020kfyXGYJ037,China)
文摘SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths.There are currently no registered therapies for treating coronavirus infections.Because of time consuming process of new drug development,drug repositioning may be the only solution to the epidemic of sudden infectious diseases.We systematically analyzed all the proteins encoded by SARS-CoV-2 genes,compared them with proteins from other coronavirnses,predicted their structures,and built 19 structures that could be done by homology modeling.By performing target-based virtual ligand screening,a total of21 targets(including two human targets)were screened against compound libraries including ZINC drug database and our own database of natural products.Structure and screening results of important targets such as 3-chymotrypsin-like protease(3 CLpro),Spike,RNA-dependent RNA polymerase(RdRp),and papain like protease(PLpro)were discussed in detail.In addition,a database of 78 commonly used antiviral drugs including those currently on the market and undergoing clinical trials for SARS-CoV-2 was constructed.Possible targets of these compounds and potential drugs acting on a certain target were predicted.This study will provide new lead compounds and targets for further in vitro and in vivo studies of SARS-CoV-2,new insights for those drugs currently ongoing clinical studies,and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections.
