The sudden outbreak of severe acute respiratory syndrome (SARS) in 2002 prompted the establishment of a global scientific network subsuming most of the traditional rivalries in the competitive field of virology. Withi...The sudden outbreak of severe acute respiratory syndrome (SARS) in 2002 prompted the establishment of a global scientific network subsuming most of the traditional rivalries in the competitive field of virology. Within months of the SARS outbreak, collaborative work revealed the identity of the disastrous pathogen as SARS-associated coronavirus (SARS-CoV). However, although the rapid identifi-展开更多
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
Coronaviruses are among the largest group of known positive-sense RNA viruses with a wide range of animal hosts as reservoir. In the last two decades,newly evolved coronaviruses such as the severe acute respiratory sy...Coronaviruses are among the largest group of known positive-sense RNA viruses with a wide range of animal hosts as reservoir. In the last two decades,newly evolved coronaviruses such as the severe acute respiratory syndrome coronavirus(SARS-CoV) which caused the infamous 2002 outbreak, the Middle East respiratory syndrome coronavirus(MERS-CoV) which caused an outbreak in 2012, and now the SARS-CoV-2 [responsible for the current coronavirus disease 2019(COVID-19)] have all posed notable threats to global public health.But, how does the current COVID-19 outbreak compare with previous coronaviruses diseases? In this review, we look at the key differences between SARS-CoV, MERS-CoV, and SARS-CoV-2, and examine challenges in determining accurate estimates of the severity of COVID-19. We discuss coronavirus outbreaks in light of key outbreak severity indicators including,disease fatality, pathogen novelty, ease of transmission, geographical range, and outbreak preparedness. Finally, we review clinical trials of emerging treatment modalities and provide recommendations on the control of COVID-19 based on the mode of transmission of the coronaviruses. We also recommend the development and use of a standardized predictive epidemic severity models to inform future epidemic response.展开更多
Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)has affected millions of people across the world engendering an unprecedented pandemic.Coronavirus disease(COVID)-19 can present asymptomatic or in the form o...Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)has affected millions of people across the world engendering an unprecedented pandemic.Coronavirus disease(COVID)-19 can present asymptomatic or in the form of the acute respiratory syndrome,viral pneumonia,or sepsis.Due to the novelty of the disease,the endocrine manifestations are not fully understood.It becomes indispensable to address the underlying endocrine disruptions contributing to the severe form of illness and thereby increasing the mortality.We discuss here the SARS-CoV-2 virus and endocrine reverberations based on the research with structurally similar SARS-COV-1.SARS-CoV-2 enters the body via its attachment to the angiotensin-converting enzyme 2(ACE2)receptors.Apart from lungs,ACE2 expression on various organs can lead to endocrine perturbations.In COVID-19 infection,pre-existing endocrine disorders warrant cautious management and may require replacement therapy.COVID-19 and its repercussions on hormones are discussed extensively in this review.展开更多
COVID-19 disease is a global pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) that mainly presents with pneumonia, but has variable multi-systemic manifestations. Concomitant bacterial in...COVID-19 disease is a global pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) that mainly presents with pneumonia, but has variable multi-systemic manifestations. Concomitant bacterial infections associated with the acute stage of COVID-19 disease have been rarely reported in the literature. However, to our knowledge, post viral organizing pneumonia (OP) secondary to bacterial infection after recovery from SARS-CoV2 infection has not been noted before. We report a 27-year-old male patient with Type 1 Diabetes Mellitus who presented with fever post recovery from COVID-19 disease for seven weeks and was found to have OP secondary to<em> Klebsiella pneumoniae</em>. Furthermore, the bronchoalveolar lavage was positive for SARS-CoV2 by RT-PCR despite multiple negative nasopharyngeal RT-PCR. The patient was successfully treated with antibiotics only. Therefore, we conclude that early recognition of OP secondary to bacterial infection in patients with COVID-19 disease and prompt antibiotic treatment could avoid the use of a prolonged course of steroids.展开更多
Severe acute respiratory syndrome(SARS)is a highly contagious zoonotic disease caused by SARS coronavirus(SARS-Co V).Since its outbreak in Guangdong Province of China in 2002,SARS has caused 8096 infections and774 dea...Severe acute respiratory syndrome(SARS)is a highly contagious zoonotic disease caused by SARS coronavirus(SARS-Co V).Since its outbreak in Guangdong Province of China in 2002,SARS has caused 8096 infections and774 deaths by December 31st,2003.Although there have been no more SARS cases reported in human populations since 2004,the recent emergence of a novel coronavirus disease(COVID-19)indicates the potential of the recurrence of SARS and other coronavirus disease among humans.Thus,developing a rapid response SARS vaccine to provide protection for human populations is still needed.Spike(S)protein of SARS-Co V can induce neutralizing antibodies,which is a pivotal immunogenic antigen for vaccine development.Here we constructed a recombinant chimeric vesicular stomatitis virus(VSV)VSVΔG-SARS,in which the glycoprotein(G)gene is replaced with the SARS-Co V S gene.VSVΔG-SARS maintains the bullet-like shape of the native VSV,with the heterogeneous S protein incorporated into its surface instead of G protein.The results of safety trials revealed that VSVΔG-SARS is safe and effective in mice at a dose of 1×10^(6)TCID_(50).More importantly,only a single-dose immunization of 2×10^(7)TCID_(50)can provide high-level neutralizing antibodies and robust T cell responses to non-human primate animal models.Thus,our data indicate that VSVΔG-SARS can be used as a rapid response vaccine candidate.Our study on the recombinant VSV-vectored SARS-Co V vaccines can accumulate experience and provide a foundation for the new coronavirus disease in the future.展开更多
The sudden emergence of severe acute respiratory syndrome coronavirus(SARS-CoV) has caused global panic in 2003,and the risk of SARS-CoV outbreak still exists. However, no specific antiviral drug or vaccine is availab...The sudden emergence of severe acute respiratory syndrome coronavirus(SARS-CoV) has caused global panic in 2003,and the risk of SARS-CoV outbreak still exists. However, no specific antiviral drug or vaccine is available;thus, the development of therapeutic antibodies against SARS-CoV is needed. In this study, a nanobody phage-displayed library was constructed from peripheral blood mononuclear cells of alpacas immunized with the recombinant receptor-binding domain(RBD) of SARS-CoV. Four positive clones were selected after four rounds of bio-panning and subjected to recombinant expression in E. coli. Further biological identification demonstrated that one of the nanobodies, S14, showed high affinity to SARS-CoV RBD and potent neutralization activity at the picomole level against SARS-CoV pseudovirus. A competitive inhibition assay showed that S14 blocked the binding of SARS-CoV RBD to either soluble or cell-expressed angiotensinconverting enzyme 2(ACE2). In summary, we developed a novel nanobody targeting SARS-CoV RBD, which might be useful for the development of therapeutics against SARS.展开更多
The spike protein of the severe acute respiratory syndrome coronavirus （SARS-CoV） mediates cell fusion by binding to target cell surface receptors. This paper reports a simple method for dissecting the viral protein...The spike protein of the severe acute respiratory syndrome coronavirus （SARS-CoV） mediates cell fusion by binding to target cell surface receptors. This paper reports a simple method for dissecting the viral protein and for searching for foldable fragments in a random but systematic manner. The method involves digestion by DNase I to generate a pool of short DNA segments, followed by an additional step of reassembly of these segments to produce a library of DNA fragments with random ends but controllable lengths. To rapidly screen for discrete folded polypeptide fragments, the reassembled gene fragments were further cloned into a vector as N-terminal fusions to a folding reporter gene which was a variant of green fluorescent protein. Two foldable fragments were identified for the SARS-CoV spike protein, which coincide with various anti-SARS peptides derived from the hepated repeat （HR） region 2 of the spike protein. The method should be applicable to other viral proteins to isolate antigen or vaccine candidates, thus providing an alternative to the full-length proteins （subunits） or linear short peptides.展开更多
基金This work was supported by Research Grant Council Grant HKU 7553/03M and The University of Hong Kong.
文摘The sudden outbreak of severe acute respiratory syndrome (SARS) in 2002 prompted the establishment of a global scientific network subsuming most of the traditional rivalries in the competitive field of virology. Within months of the SARS outbreak, collaborative work revealed the identity of the disastrous pathogen as SARS-associated coronavirus (SARS-CoV). However, although the rapid identifi-
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.
文摘Coronaviruses are among the largest group of known positive-sense RNA viruses with a wide range of animal hosts as reservoir. In the last two decades,newly evolved coronaviruses such as the severe acute respiratory syndrome coronavirus(SARS-CoV) which caused the infamous 2002 outbreak, the Middle East respiratory syndrome coronavirus(MERS-CoV) which caused an outbreak in 2012, and now the SARS-CoV-2 [responsible for the current coronavirus disease 2019(COVID-19)] have all posed notable threats to global public health.But, how does the current COVID-19 outbreak compare with previous coronaviruses diseases? In this review, we look at the key differences between SARS-CoV, MERS-CoV, and SARS-CoV-2, and examine challenges in determining accurate estimates of the severity of COVID-19. We discuss coronavirus outbreaks in light of key outbreak severity indicators including,disease fatality, pathogen novelty, ease of transmission, geographical range, and outbreak preparedness. Finally, we review clinical trials of emerging treatment modalities and provide recommendations on the control of COVID-19 based on the mode of transmission of the coronaviruses. We also recommend the development and use of a standardized predictive epidemic severity models to inform future epidemic response.
文摘Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)has affected millions of people across the world engendering an unprecedented pandemic.Coronavirus disease(COVID)-19 can present asymptomatic or in the form of the acute respiratory syndrome,viral pneumonia,or sepsis.Due to the novelty of the disease,the endocrine manifestations are not fully understood.It becomes indispensable to address the underlying endocrine disruptions contributing to the severe form of illness and thereby increasing the mortality.We discuss here the SARS-CoV-2 virus and endocrine reverberations based on the research with structurally similar SARS-COV-1.SARS-CoV-2 enters the body via its attachment to the angiotensin-converting enzyme 2(ACE2)receptors.Apart from lungs,ACE2 expression on various organs can lead to endocrine perturbations.In COVID-19 infection,pre-existing endocrine disorders warrant cautious management and may require replacement therapy.COVID-19 and its repercussions on hormones are discussed extensively in this review.
文摘COVID-19 disease is a global pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) that mainly presents with pneumonia, but has variable multi-systemic manifestations. Concomitant bacterial infections associated with the acute stage of COVID-19 disease have been rarely reported in the literature. However, to our knowledge, post viral organizing pneumonia (OP) secondary to bacterial infection after recovery from SARS-CoV2 infection has not been noted before. We report a 27-year-old male patient with Type 1 Diabetes Mellitus who presented with fever post recovery from COVID-19 disease for seven weeks and was found to have OP secondary to<em> Klebsiella pneumoniae</em>. Furthermore, the bronchoalveolar lavage was positive for SARS-CoV2 by RT-PCR despite multiple negative nasopharyngeal RT-PCR. The patient was successfully treated with antibiotics only. Therefore, we conclude that early recognition of OP secondary to bacterial infection in patients with COVID-19 disease and prompt antibiotic treatment could avoid the use of a prolonged course of steroids.
基金supported by grants from the National Key Research and Development Program of China(2017YFD0501804)。
文摘Severe acute respiratory syndrome(SARS)is a highly contagious zoonotic disease caused by SARS coronavirus(SARS-Co V).Since its outbreak in Guangdong Province of China in 2002,SARS has caused 8096 infections and774 deaths by December 31st,2003.Although there have been no more SARS cases reported in human populations since 2004,the recent emergence of a novel coronavirus disease(COVID-19)indicates the potential of the recurrence of SARS and other coronavirus disease among humans.Thus,developing a rapid response SARS vaccine to provide protection for human populations is still needed.Spike(S)protein of SARS-Co V can induce neutralizing antibodies,which is a pivotal immunogenic antigen for vaccine development.Here we constructed a recombinant chimeric vesicular stomatitis virus(VSV)VSVΔG-SARS,in which the glycoprotein(G)gene is replaced with the SARS-Co V S gene.VSVΔG-SARS maintains the bullet-like shape of the native VSV,with the heterogeneous S protein incorporated into its surface instead of G protein.The results of safety trials revealed that VSVΔG-SARS is safe and effective in mice at a dose of 1×10^(6)TCID_(50).More importantly,only a single-dose immunization of 2×10^(7)TCID_(50)can provide high-level neutralizing antibodies and robust T cell responses to non-human primate animal models.Thus,our data indicate that VSVΔG-SARS can be used as a rapid response vaccine candidate.Our study on the recombinant VSV-vectored SARS-Co V vaccines can accumulate experience and provide a foundation for the new coronavirus disease in the future.
基金This study was supported by SKLPBS1805 and 2019-JCJQ-JJ-167(to G.Z.)supported by the National Science Fund for Distinguished Young Scholar(No.81925025)+1 种基金the Innovative Research Group(No.81621005)from the NSFCthe Innovation Fund for Medical Sciences(No.2019-I2M-5-049)from the Chinese Academy of Medical Sciences。
文摘The sudden emergence of severe acute respiratory syndrome coronavirus(SARS-CoV) has caused global panic in 2003,and the risk of SARS-CoV outbreak still exists. However, no specific antiviral drug or vaccine is available;thus, the development of therapeutic antibodies against SARS-CoV is needed. In this study, a nanobody phage-displayed library was constructed from peripheral blood mononuclear cells of alpacas immunized with the recombinant receptor-binding domain(RBD) of SARS-CoV. Four positive clones were selected after four rounds of bio-panning and subjected to recombinant expression in E. coli. Further biological identification demonstrated that one of the nanobodies, S14, showed high affinity to SARS-CoV RBD and potent neutralization activity at the picomole level against SARS-CoV pseudovirus. A competitive inhibition assay showed that S14 blocked the binding of SARS-CoV RBD to either soluble or cell-expressed angiotensinconverting enzyme 2(ACE2). In summary, we developed a novel nanobody targeting SARS-CoV RBD, which might be useful for the development of therapeutics against SARS.
基金Supported by the Tsinghua University SARS Special Fund and theNational Key Basic Research and Development (973) Program of China (No. 2003CB716002)
文摘The spike protein of the severe acute respiratory syndrome coronavirus （SARS-CoV） mediates cell fusion by binding to target cell surface receptors. This paper reports a simple method for dissecting the viral protein and for searching for foldable fragments in a random but systematic manner. The method involves digestion by DNase I to generate a pool of short DNA segments, followed by an additional step of reassembly of these segments to produce a library of DNA fragments with random ends but controllable lengths. To rapidly screen for discrete folded polypeptide fragments, the reassembled gene fragments were further cloned into a vector as N-terminal fusions to a folding reporter gene which was a variant of green fluorescent protein. Two foldable fragments were identified for the SARS-CoV spike protein, which coincide with various anti-SARS peptides derived from the hepated repeat （HR） region 2 of the spike protein. The method should be applicable to other viral proteins to isolate antigen or vaccine candidates, thus providing an alternative to the full-length proteins （subunits） or linear short peptides.
