While severe acute respiratory syndrome coronavirus （SARS-CoV）~as initially thought to enter cells through direct fusion with the plasma membrane, more recent evidence suggests that yirus entry may also involve endo...While severe acute respiratory syndrome coronavirus （SARS-CoV）~as initially thought to enter cells through direct fusion with the plasma membrane, more recent evidence suggests that yirus entry may also involve endocytosis. We have found that SARS-CoV enters cells viapH- and receptor-dependent endocytosis. Treatment of cells with either SARS-COV spike protein or spike-bearing pseudoviruses resulted in the translocation of angiotensin-converting enzyme 2 （ACE2）, the functional receptor of SARS-CoV, from the cell surface to endosomes. In addition, the spike-bearing pseudoviruses and early endosome antigen 1 were found to colocalize in endosomes. Further analyses using specific endocytic path- way inhibitors and dominant-negative Epsl5 as well as caveolin-1 colocalization study suggested that virus entry was mediated by a clathrin- and caveolae-independent mechanism. Moreover, cholesterol- and sphingolipid-rich lipid raft microdomains in the plasma membrane, which have been shown to act as platforms for many physiological signaling pathways, were shown to be involved in virus entry. Endocytic entry of SARS-CoV may expand the cellular range of SARS-CoV infection, and our findings here contribute to the understanding of SARS-CoV pathogenesis, providing new information for anti-viral drug research.展开更多
In 2003,severe acute respiratory syndrome coronavirus（SARS-CoV）emerged in Guangdong Province,China,infected more than 8000 individuals,and resulted in a 10%mortality rate（Rota et al.2003）.Later,in 2012,a novel CoV...In 2003,severe acute respiratory syndrome coronavirus（SARS-CoV）emerged in Guangdong Province,China,infected more than 8000 individuals,and resulted in a 10%mortality rate（Rota et al.2003）.Later,in 2012,a novel CoV,Middle East respiratory syndrome coronavirus（MERS-CoV）,was isolated from the sputum of a man in Saudi Arabia（Perl et al.2014）.Notably,MERS-CoV recently reemerged in the Republic of Korea, and killed 36 out of 186 confirmed cases （Korea Centers for Disease Control and Prevention 2015）. Therefore, SARS-CoV still carries the potential for resurgence; efforts are being made to prevent the recurrence of an epidemic.展开更多
Coronaviruses(CoVs),a family of enveloped positive-sense RNA viruses,are characterized by club-like spikes that project from their surface,unusually large RNA genome,and unique replication capability.Co Vs are known t...Coronaviruses(CoVs),a family of enveloped positive-sense RNA viruses,are characterized by club-like spikes that project from their surface,unusually large RNA genome,and unique replication capability.Co Vs are known to cause various potentially lethal human respiratory infectious diseases,such as severe acute respiratory syndrome(SARS),Middle East respiratory syndrome(MERS),and the very recent coronavirus disease 2019(COVID-19)outbreak.Unfortunately,neither drug nor vaccine has yet been approved to date to prevent and treat these diseases caused by CoVs.Therefore,effective prevention and treatment medications against human coronavirus are in urgent need.In the past decades,many natural compounds have been reported to possess multiple biological activities,including antiviral properties.In this article,we provided a comprehensive review on the natural compounds that interfere with the life cycles of SARS and MERS,and discussed their potential use for the treatment of COVID-19.展开更多
Based on the announcement of the World Health Organization(WHO) in 2018, the Wuhan pneumonia caused by an unknown etiology should be recognized as the first Disease X. Later, the pathogen was identified to be a novel ...Based on the announcement of the World Health Organization(WHO) in 2018, the Wuhan pneumonia caused by an unknown etiology should be recognized as the first Disease X. Later, the pathogen was identified to be a novel coronavirus denoted 2019-nCoV, which has 79.5% and 96% whole genome sequence identify to SARS-CoV and bat SARS-related coronavirus(SARSr-CoV-RaTG13), respectively, suggesting its potential bat origin. With high human-to-human transmission rate(R0), 2019-nCoV has quickly spread in China and other countries, resulting in 34,953 confirmed cases and 725 deaths as of 8 February 2020, thus calling for urgent development of therapeutics and prophylactics. Here we suggest renaming 2019-nCoV as "transmissible acute respiratory syndrome coronavirus(TARS-CoV)" and briefly review the advancement of research and development of neutralizing antibodies and vaccines targeting the receptor-binding domain(RBD) and viral fusion inhibitors targeting the heptad repeat 1(HR1) domain in spike protein of 2019-nCoV.展开更多
文摘While severe acute respiratory syndrome coronavirus （SARS-CoV）~as initially thought to enter cells through direct fusion with the plasma membrane, more recent evidence suggests that yirus entry may also involve endocytosis. We have found that SARS-CoV enters cells viapH- and receptor-dependent endocytosis. Treatment of cells with either SARS-COV spike protein or spike-bearing pseudoviruses resulted in the translocation of angiotensin-converting enzyme 2 （ACE2）, the functional receptor of SARS-CoV, from the cell surface to endosomes. In addition, the spike-bearing pseudoviruses and early endosome antigen 1 were found to colocalize in endosomes. Further analyses using specific endocytic path- way inhibitors and dominant-negative Epsl5 as well as caveolin-1 colocalization study suggested that virus entry was mediated by a clathrin- and caveolae-independent mechanism. Moreover, cholesterol- and sphingolipid-rich lipid raft microdomains in the plasma membrane, which have been shown to act as platforms for many physiological signaling pathways, were shown to be involved in virus entry. Endocytic entry of SARS-CoV may expand the cellular range of SARS-CoV infection, and our findings here contribute to the understanding of SARS-CoV pathogenesis, providing new information for anti-viral drug research.
基金supported by the Chinese Medicine Foundation and Opening Foundation of State Key Laboratory of Virology,Wuhan University (No.2016KF010)
文摘In 2003,severe acute respiratory syndrome coronavirus（SARS-CoV）emerged in Guangdong Province,China,infected more than 8000 individuals,and resulted in a 10%mortality rate（Rota et al.2003）.Later,in 2012,a novel CoV,Middle East respiratory syndrome coronavirus（MERS-CoV）,was isolated from the sputum of a man in Saudi Arabia（Perl et al.2014）.Notably,MERS-CoV recently reemerged in the Republic of Korea, and killed 36 out of 186 confirmed cases （Korea Centers for Disease Control and Prevention 2015）. Therefore, SARS-CoV still carries the potential for resurgence; efforts are being made to prevent the recurrence of an epidemic.
文摘Coronaviruses(CoVs),a family of enveloped positive-sense RNA viruses,are characterized by club-like spikes that project from their surface,unusually large RNA genome,and unique replication capability.Co Vs are known to cause various potentially lethal human respiratory infectious diseases,such as severe acute respiratory syndrome(SARS),Middle East respiratory syndrome(MERS),and the very recent coronavirus disease 2019(COVID-19)outbreak.Unfortunately,neither drug nor vaccine has yet been approved to date to prevent and treat these diseases caused by CoVs.Therefore,effective prevention and treatment medications against human coronavirus are in urgent need.In the past decades,many natural compounds have been reported to possess multiple biological activities,including antiviral properties.In this article,we provided a comprehensive review on the natural compounds that interfere with the life cycles of SARS and MERS,and discussed their potential use for the treatment of COVID-19.
文摘Based on the announcement of the World Health Organization(WHO) in 2018, the Wuhan pneumonia caused by an unknown etiology should be recognized as the first Disease X. Later, the pathogen was identified to be a novel coronavirus denoted 2019-nCoV, which has 79.5% and 96% whole genome sequence identify to SARS-CoV and bat SARS-related coronavirus(SARSr-CoV-RaTG13), respectively, suggesting its potential bat origin. With high human-to-human transmission rate(R0), 2019-nCoV has quickly spread in China and other countries, resulting in 34,953 confirmed cases and 725 deaths as of 8 February 2020, thus calling for urgent development of therapeutics and prophylactics. Here we suggest renaming 2019-nCoV as "transmissible acute respiratory syndrome coronavirus(TARS-CoV)" and briefly review the advancement of research and development of neutralizing antibodies and vaccines targeting the receptor-binding domain(RBD) and viral fusion inhibitors targeting the heptad repeat 1(HR1) domain in spike protein of 2019-nCoV.
基金supported as the Key Medical Research Project for SARS Prevention sponsored by the Ministry of Science and Technology of China and by Guangdong Province
