Coronaviruses are single-stranded,positive-sense RNA enveloped viruses that have posed a significant threat to human health over the past few decades,particularly severe acute respiratory syndrome coronavirus(SARS-CoV...Coronaviruses are single-stranded,positive-sense RNA enveloped viruses that have posed a significant threat to human health over the past few decades,particularly severe acute respiratory syndrome coronavirus(SARS-CoV),Middle East respiratory syndrome coronavirus(MERS-CoV),and SARS-CoV-2.These viruses have caused widespread infections and fatalities,with profound impacts on global economies,social life,and public health systems.Due to their broad host range in natural settings and the consequent high potential for zoonotic spillover events,a thorough investigation of the common viral mechanisms and the identification of druggable targets for pan-coronavirus antiviral development are of utmost importance.展开更多
Since the outbreak of novel coronavirus pneumonia(coronavirus disease 2019,COVID-19),it has rapidly spread to 187 countries,causing serious harm to the health of people and a huge social burden.However,currently,drugs...Since the outbreak of novel coronavirus pneumonia(coronavirus disease 2019,COVID-19),it has rapidly spread to 187 countries,causing serious harm to the health of people and a huge social burden.However,currently,drugs specifically approved for clinical use are not available,except for vaccines against COVID-19 that are being evaluated.Traditional Chinese medicine(TCM)is capable of performing syndrome differentiation and treatment according to the clinical manifestations of patients,and has a better ability of epidemic prevention and control.The authors comprehensively analyzed the etiology and pathogenesis of COVID-19 based on the theory of TCM,and discussed its syndrome differentiation,treatment and prevention measures so as to provide strategies and reference for the prevention and treatment with TCM.展开更多
Porcine deltacoronavirus(PDCoV)is a swine enteropathogenic CoV that causes severe vomiting,diarrhea and dehydration in suckling piglets,leading to economic losses in the swine industry.There is a great need for a conv...Porcine deltacoronavirus(PDCoV)is a swine enteropathogenic CoV that causes severe vomiting,diarrhea and dehydration in suckling piglets,leading to economic losses in the swine industry.There is a great need for a convenient method to detect circulating antibodies and help in accurate diagnosis and disease control.Previously,we demonstrated that a unique PDCoV accessory protein,NS6,is expressed during PDCoV infection in pigs and is incorporated into PDCoV virions;thus,we deduced that NS6 is likely an immunogenic target that can be used for the diagnosis of PDCoV infection.In this study,we first confirmed that NS6 is immunogenic in PDCoV-infected pigs by perform-ing a serum western blot.Furthermore,we developed a novel NS6-based indirect enzyme-linked immunosorbent assay(iELISA)method and compared it to an established S1-based iELISA for the survey of anti-PDCoV IgG or IgA in pigs of different ages in China.The NS6-iELISA has high specificity for the detection of IgG antibodies and no cross-reactivity with other porcine enteric CoVs(transmissible gastroenteritis coronavirus,porcine epidemic diarrhea virus,or swine acute diarrhea syndrome coronavirus).This NS6 serology-based method has great sensitivity and good repeatability,making it a new and cost-saving option for the rapid diagnosis and immunosurveillance of PDCoV,which may also be important for the prevention and control of deltacoronavirus-related infection in pigs and other animals.展开更多
Objective:This review aimed to identify the barriers and facilitators to equitable coronavirus disease 2019(COVID-19)vaccine distribution in Nigeria using the consolidated framework for implementation research(CFIR).M...Objective:This review aimed to identify the barriers and facilitators to equitable coronavirus disease 2019(COVID-19)vaccine distribution in Nigeria using the consolidated framework for implementation research(CFIR).Methods:A comprehensive search strategy was applied across five databases—Web of Science,MEDLINE,EMBASE,CAB Direct,and CINAHL.The search,conducted as part of a scoping review,yielded 2,751 citations.Seven studies met the inclusion criteria after screening.Data were extracted and analyzed using CFIR constructs to identify key barriers and facilitators to equitable vaccine distribution.Results:Six barriers were identified:limited physical and socioeconomic access,bribery,nepotism,and insufficient availability of translated information.Facilitators included community involvement as local monitoring agents,unannounced staff inspections,healthcare worker training tailored to community needs,and localized outreach strategies such as jingles and call-in programs.CFIR constructs,including Local Conditions,Tailoring Strategies,Available Resources,and Physical Infrastructure,provided a framework for analyzing the findings.Conclusion:This review highlights significant barriers and promising facilitators to equitable vaccine distribution in Nigeria.Targeted interventions,such as community engagement,anti-corruption measures,and culturally tailored strategies,are critical to addressing these challenges and improving access.These findings underscore the need for localized,equity-focused approaches to enhance vaccine distribution systems in Nigeria and other low-resource settings.展开更多
BACKGROUND The coronavirus disease 2019(COVID-19)pandemic had a profound societal impact in the United States which was associated with a decrease in overall life expectancy and an increase in substance abuse and fire...BACKGROUND The coronavirus disease 2019(COVID-19)pandemic had a profound societal impact in the United States which was associated with a decrease in overall life expectancy and an increase in substance abuse and firearm injury.Our under-standing of changes in mortality trends during the pandemic and its effect on organ availability for transplantation is limited.AIM To examine the trends of substance abuse and firearm injury fatalities during COVID-19 and a potential correlation with organ transplantation.METHODS Crude rates of population-based deaths among adults(18-75 years)from firearm injury and substance abuse from the period of 2014-2021 were obtained from centers of disease control wide-ranging online data for epidemiologic research database.Crude rates of causes of donor(18-75 years)deaths from 2014-2021 were obtained from the united network for organ sharing database.RESULTS Average annual percentage change(AAPC)deaths among the United States population were 16.4%from substance abuse and 3.4%from firearm injury.AAPC in cause of death among organ donors was 10.9%from drug intoxication and 2.1%from firearm injury.There was a significant(P<0.001)and progressive increase in mortality from both causes during the pandemic(2020-2021)and significant correlation(P<0.001)between population and donor causes of death.COVID-19 exacerbated trends in substance abuse and firearm mortality with a consequent increase in organ donation from donors who died from these two causes.CONCLUSION Identifying the socioeconomic and regional disparities associated with increase in deaths from substance abuse and firearms can help guide post-pandemic healthcare policies and mitigate their impact on organ transplantation.展开更多
The 3CL protease, a highly conserved enzyme in the coronavirus, plays a crucial role in the viral life cycle by facilitating viral replication through precise cleavage of polyproteins. Beyond its proteolytic function,...The 3CL protease, a highly conserved enzyme in the coronavirus, plays a crucial role in the viral life cycle by facilitating viral replication through precise cleavage of polyproteins. Beyond its proteolytic function, the 3CL protease also engages in intricate interactions with host cell proteins involved in critical cellular processes such as transcription, translation, and nuclear-cytoplasmic transport, effectively hijacking cellular machinery to promote viral replication. Additionally, it disrupts innate immune signaling pathways, suppresses interferon activity and cleaves antiviral proteins. Furthermore, it modulates host cell death pathways including pyroptosis and apoptosis, interferes with autophagy and inhibits stress granule formation to maintain viral infection and exacerbate viral pathogenesis. This review highlights the molecular mechanisms by which the 3CL protease orchestrates virus-host interactions, emphasizing its central role in coronavirus pathogenesis and highlighting potential therapeutic targets for future interventions.展开更多
We report the development of a triplex nucleic acid lateral flow immunoassay(NALFIA)for the detection of the genomes of Nipah virus(NiV),Middle East respiratory syndrome coronavirus(MERS-CoV)and Reston ebolavirus(REBO...We report the development of a triplex nucleic acid lateral flow immunoassay(NALFIA)for the detection of the genomes of Nipah virus(NiV),Middle East respiratory syndrome coronavirus(MERS-CoV)and Reston ebolavirus(REBOV),which are intended for screening bats as well as other hosts and reservoirs of these three viruses.Our triplex NALFIA is a two-step assay format:the target nucleic acid in the sample is first amplified using tagged primers,and the tagged dsDNA amplicons are captured by antibodies immobilized on the NALFIA device,resulting in signal development from the binding of a streptavidin-colloidal gold conjugate to a biotin tag on the captured amplicons.Triplex amplification of the N gene of NiV,the UpE gene of MERS-CoV,and the Vp40 gene of REBOV was optimized,and three compatible combinations of hapten labels and antibodies were identified for end point detection.The lowest RNA copy numbers detected by the triplex NALFIA were 8.21e4 for the NiV N target,7.09e1 for the MERS-CoV UpE target,and 1.83e4 for the REBOV Vp40 target.Using simulated samples,the sensitivity and specificity for MERS-CoV and REBOV targets were estimated to be 100%,while the sensitivity and specificity for the NiV target were 91%and 93.3%,respectively.The compliance rate between triplex NALFIA and real-time RT‒PCR was 92%for the NiV N target and 100%for the MERS-CoV UpE and REBOV Vp40 targets.展开更多
The current corona virus disease 2019 outbreak caused by severe acute respiratory syndrome coronavirus 2 started in Wuhan,China in December 2019 and has put the world on alert.To safeguard Chinese citizens and to stre...The current corona virus disease 2019 outbreak caused by severe acute respiratory syndrome coronavirus 2 started in Wuhan,China in December 2019 and has put the world on alert.To safeguard Chinese citizens and to strengthen global health security,China has made great efforts to control the epidemic.Many in the global community have joined China to limit the epidemic.However,discrimination and prejudice driven by fear or misinformation have been flowing globally,superseding evidence and jeopardizing the anti-severe acute respiratory syndrome coronavirus 2 efforts.We analyze this phenomenon and its underlying causes and suggest practical solutions.展开更多
The effects of coronaviruses on the respiratory system are of great concern,but their effects on the digestive system receive much less attention.Coronaviruses that infect mammals have shown gastrointestinal pathogeni...The effects of coronaviruses on the respiratory system are of great concern,but their effects on the digestive system receive much less attention.Coronaviruses that infect mammals have shown gastrointestinal pathogenicity and caused symptoms such as diarrhea and vomiting.Available data have shown that human coronaviruses,including the newly emerged SARS-CoV-2,mainly infect the respiratory system and cause symptoms such as cough and fever,while they may generate gastrointestinal symptoms.However,there is little about the relation between coronavirus and digestive system.This review specifically addresses the effects of mammalian and human coronaviruses,including SARS-CoV-2,on the digestive tract,helping to cope with the new virus infection-induced disease,COVID-19.展开更多
Although the coronavirus disease 2019(COVID-19)epidemic is still ongoing,vaccination rates are rising slowly and related treatments and drugs are being developed.At the same time,there is increasing evidence of preexi...Although the coronavirus disease 2019(COVID-19)epidemic is still ongoing,vaccination rates are rising slowly and related treatments and drugs are being developed.At the same time,there is increasing evidence of preexisting immunity against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)in humans,mainly consisting of preexisting antibodies and immune cells(including T cells and B cells).The presence of these antibodies is mainly due to the seasonal prevalence of four common coronavirus types,especially OC43 and HKU1.The accumulated relevant evidence has suggested that the target of antibodies is mainly the S2 subunit of S protein,followed by evolutionary conservative regions such as the nucleocapsid(N)protein.Additionally,preexisting memory T and B cells are also present in the population.Preexisting antibodies can help the body protect against SARS-CoV-2 infection,reduce the severity of COVID-19,and rapidly increase the immune response post-infection.These multiple effects can directly affect disease progression and even the likelihood of death in certain individuals.Besides the positive effects,preexisting immunity may also have negative consequences,such as antibody-dependent enhancement(ADE)and original antigenic sin(OAS),the prevalence of which needs to be further established.In the future,more research should be focused on evaluating the role of preexisting immunity in COVID-19 outcomes,adopting appropriate policies and strategies for fighting the pandemic,and vaccine development that considers preexisting immunity.展开更多
Objective:To investigate the genetic diversity of coronaviruses in wild and domestic birds in the bird park and live poultry markets of Ca Mau province in Vietnam in 2020.Methods:A total of 228 samples(121 from wild b...Objective:To investigate the genetic diversity of coronaviruses in wild and domestic birds in the bird park and live poultry markets of Ca Mau province in Vietnam in 2020.Methods:A total of 228 samples(121 from wild birds and 107 from poultry)were collected in the territory of Ca Mau province of Vietnam in 2020.The avian samples were tested for the presence of the four genera of coronaviruses using reverse transcription and nested PCR.Molecular genetic analysis using targeted NGS sequencing of RdRp gene was performed for 29 representative samples(12 samples from wild birds and 17 from poultry).Phylogenetic analysis was performed using the neighbour joininig method with 1000 bootstrap replications using MEGA X software.Results:Among wild birds,21.5%samples were positive for the genetic material of coronaviruses and 38.3%samples were positive for coronaviruses among poultry.Genetic analysis of the partial sequence of RdRp gene from representative samples revealed that wild birds were carriers of gammacoronaviruses and deltacoronaviruses.Among poultry,three genotypes of infectious bronchitis virus(QX,Mass and Q1)were detected in chickens,with QX genotypes being predominant,and viruses of DCoV group were detected in domestic ducks.There was no detection of alphacoronaviruses or betacoronaviruses in the studied birds.Conclusions:Coronaviruses of genera Gammacoronavirus and Deltacoronavirus were detected in wild birds.A high percentage of infectious bronchitis virus was detected in poultry.Thus,there is a need for broader surveillance of coronaviruses in birds,which can be used for evaluation of diversity,evolution and distribution of coronaviruses in Vietnam.Continuous surveillance of coronaviruses circulation in wild and domestic animals is necessary for implementing strategic measures for poultry and domestic animal protection and for evaluation of possible risk of circulating coronaviruses to human health.展开更多
In order to survey the infectious situation of canine coronavirus (CCV) in giant panda population, a virus neutralization test detecting specific antibodies against CCV in giant panda抯 sera was established by using t...In order to survey the infectious situation of canine coronavirus (CCV) in giant panda population, a virus neutralization test detecting specific antibodies against CCV in giant panda抯 sera was established by using two-fold dilutions of serum and 100 TCID50 of the virus. The 62 sera samples of giant pandas, which were gathered from zoos and reserve region of Sichuan Province, China were detected. The neutralization antibody titer of 1:4 was recognized as the positive criterion, 8 sera samples were detected to be positive, and the positive rate was 12.9%. The titers of neutralizing antibody ranged from 1:8 to 1:32. It was the first comprehensive investigation on neutralization antibodies against CCV in giant panda population in China. The results of study showed that the infection of CCV in giant panda population was universal, which has posed a threat to the health of giant panda. Therefore, it is incumbent on us to study safe and effective vaccines to protect giant panda against CCV infection.展开更多
The novel coronavirus pneumonia broke out in 2019 and spread rapidly. In 30 different countries, there are over seventy thousand patients have been diagnosed in total. Therefore, it is urgent to develop the effective ...The novel coronavirus pneumonia broke out in 2019 and spread rapidly. In 30 different countries, there are over seventy thousand patients have been diagnosed in total. Therefore, it is urgent to develop the effective program to prevent and treat for the novel coronavirus pneumonia. In view of Traditional Chinese Medicine has accumulated a solid theoretical foundation of plague in ancient and recent decades. Meanwhile, Traditional Chinese Medicine can provide the more effective and personalized treatment via adjusting the specific medicine for each patient based on the different syndromes. In addition, TCM often has different effect on the distinct stages of diseases, contributing to the prevention, treatment and rehabilitation. Nowadays, TCM has exhibited decent effect in the in the fight against NCP. Therefore, it is convinced that Traditional Chinese Medicine is an effective treatment for 2019 novel coronavirus pneumonia.展开更多
prevalence.A number of clinical workers and researchers have made great efforts to understand the pathogenesis and clinical characteristics and develop effective drugs for treatment.However,no effective drugs with ant...prevalence.A number of clinical workers and researchers have made great efforts to understand the pathogenesis and clinical characteristics and develop effective drugs for treatment.However,no effective drugs with antiviral effects on severe acute respiratory syndrome coronavirus 2 have been discovered currently.Traditional Chinese medicine(TCM)has gained abundant experience in the treatment of infectious diseases for thousands of years.In this review,the authors summarized the clinical outcome,pathogensis and current application of TCM on coronavirus disease 2019.Further,we discussed the potential mechanisms and the future research directions of TCM against severe acute respiratory syndrome coronavirus 2.展开更多
The current pandemic of COVID-19 caused by a novel coronavirus,severe acute respiratory syndrome coronavirus-2(SARS-CoV-2),threatens human health around the world.Of particular concern is that bats are recognized as o...The current pandemic of COVID-19 caused by a novel coronavirus,severe acute respiratory syndrome coronavirus-2(SARS-CoV-2),threatens human health around the world.Of particular concern is that bats are recognized as one of the most potential natural hosts of SARS-CoV-2;however,coronavirus ecology in bats is still nascent.Here,we performed a degenerate primer screening and next-generation sequencing analysis of 112 bats,collected from Hainan Province,China.Three coronaviruses,namely bat betacoronavirus(Bat CoV)CD35,Bat CoV CD36 and bat alpha-coronavirus CD30 were identified.Bat CoV CD35 genome had 99.5%identity with Bat CoV CD36,both sharing the highest nucleotide identity with Bat Hp-betacoronavirus Zhejiang2013(71.4%),followed by SARS-CoV-2(54.0%).Phylogenetic analysis indicated that Bat CoV CD35 formed a distinct clade,and together with Bat Hp-betacoronavirus Zhejiang2013,was basal to the lineage of SARS-CoV-1 and SARS-CoV-2.Notably,Bat CoV CD35 harbored a canonical furin-like S1/S2 cleavage site that resembles the corresponding sites of SARS-CoV-2.The furin cleavage sites between CD35 and CD36 are identical.In addition,the receptor-binding domain of Bat CoV CD35 showed a highly similar structure to that of SARS-CoV-1 and SARS-CoV-2,especially in one binding loop.In conclusion,this study deepens our understanding of the diversity of coronaviruses and provides clues about the natural origin of the furin cleavage site of SARS-CoV-2.展开更多
BACKGROUND: The study aims to illustrate the clinical characteristics and development of septic shock in intensive care unit(ICU) patients confirmed with severe acute respiratory syndrome coronavirus 2(SARS-Co V-2) in...BACKGROUND: The study aims to illustrate the clinical characteristics and development of septic shock in intensive care unit(ICU) patients confirmed with severe acute respiratory syndrome coronavirus 2(SARS-Co V-2) infection, and to perform a comprehensive analysis of the association between septic shock and clinical outcomes in critically ill patients with coronavirus disease(COVID-19).METHODS: Patients confirmed with SARS-Co V-2 infection, who were admitted to the ICU of the Third People's Hospital of Shenzhen from January 1 to February 7, 2020, were enrolled. Clinical characteristics and outcomes were compared between patients with and without septic shock.RESULTS: In this study, 35 critically ill patients with COVID-19 were included. Among them, the median age was 64 years(interquartile range [IQR] 59-67 years), and 10(28.4%) patients were female. The median ICU length of stay was 16 days(IQR 8-23 days). Three(8.6%) patients died during hospitalization. Nine(25.7%) patients developed septic shock in the ICU, and these patients had a significantly higher incidence of organ dysfunction and a worse prognosis than patients without septic shock.CONCLUSIONS: Septic shock is associated with a poor outcome in critically ill COVID-19 patients and is one of the hallmarks of the severity of patients receiving ICU care. A dysregulated immune response, uncontrolled infl ammation, and coagulation disorders are strongly associated with the development and progression of COVID-19-related septic shock.展开更多
Objective Here we aimed to investigate the difference in clinical characteristics and outcomes between pediatric and adult patients with COVID-19.Methods A total of 333 consecutive patients with laboratory-confirmed S...Objective Here we aimed to investigate the difference in clinical characteristics and outcomes between pediatric and adult patients with COVID-19.Methods A total of 333 consecutive patients with laboratory-confirmed SARS-CoV-2 infection treated in the departments of Internal medicine of Shenzhen Third People’s Hospital from January 11 th to February 10 th,2020 were included.The data were obtained from electronic medical records.The epidemiological data,clinical characteristics,length of hospital stays,and outcomes of pediatric and adult patients were compared.Results Compared with adult patients,pediatric patients had a shorter time of symptom onset to hospitalization than adults[median time,1(IQR,1.0-1.0)d vs.3(IQR,2.0-6.0)d,P<0.001],milder or fewer symptoms,less severe chest CT findings.The clinical severity classification of children was less severe than adults.Up to 15 th March,the end of the follow-up,33(100%)children and 292(97.3%)adult patients had been discharged from hospital.Only 2(0.7%)adult patients died,with an overall case mortality of 0.6%.The median length of hospital stay of pediatric patients was shorter than that of adult patients[19(95%CI:16.6-21.4)d vs.21(95%CI:19.9-22.1)d,P=0.024].Conclusion Pediatric patients with COVID-19 had milder or less clinical symptoms,less evident pulmonary imaging changes,better prognosis,and shorter length of hospital stay.展开更多
BACKGROUND Since December 2019,there have been many new cases of coronavirus pneumonia in Wuhan,Hubei Province,which has gradually spread throughout the country.AIM To explore our hospital’s innovative management sys...BACKGROUND Since December 2019,there have been many new cases of coronavirus pneumonia in Wuhan,Hubei Province,which has gradually spread throughout the country.AIM To explore our hospital’s innovative management system to ensure the efficient operation of fever clinics during the epidemic,since controlling the spread of disease is an important way to prevent and control the epidemic.METHODS In total,200 outpatients with fever at our hospital between November 2019 and July 2020 were selected and allocated into two groups.RESULTS The fever clinic in our hospital operated smoothly,and infection with the novel coronavirus disease(COVID-19)has not been reported in our hospital.Additionally,we did not have any cases of missed diagnosis.The awareness regarding COVID-19 infection sources,transmission routes,early symptoms,and preventive measures was significantly higher in our fever clinic than in those of the pre-management group.CONCLUSION"An integrated system,three separate responsibilities"ensured the efficient functioning of our fever outpatient clinic and early screening of COVID-19 cases,which effectively curbed the transmission of COVID-19 and hence prevented COVID-19 pneumonia epidemic in our hospital,ultimately achieving the maximum effect of epidemic prevention and control.展开更多
The synonymous codon usage in the translational initiation and termination regions of genes of severe acute respiratory syndrome (SARS) coronavirus and five other viruses in Coronaviridae was systematically analyzed.T...The synonymous codon usage in the translational initiation and termination regions of genes of severe acute respiratory syndrome (SARS) coronavirus and five other viruses in Coronaviridae was systematically analyzed.The results indicate that most minor codons for these coronaviruses are preferentially used in the initial and terminal region.The minor codons preferentially used in the initial region are thought to have a negative effect on gene expression,which can be explained by the minor codon modulator hypothesis.It also indicates that the minor codons preferentially used in the terminal region may regulate the level of gene expression.The proposed results strongly imply that the minor codon modulator hypothesis can be applied to both some bacteria and some viruses.展开更多
A group of SARS-like coronaviruses(SL-CoV)have been identified in horseshoe bats.Despite SL-CoVs and SARS-CoV share identical genome structure and high-level sequence similarity,SL-CoV does not bind to the same cellul...A group of SARS-like coronaviruses(SL-CoV)have been identified in horseshoe bats.Despite SL-CoVs and SARS-CoV share identical genome structure and high-level sequence similarity,SL-CoV does not bind to the same cellular receptor as for SARS-CoV and the N-terminus of the S proteins only share 64%amino acid identity,suggesting there are fundamental differences between these two groups of coronaviruses.To gain insight into the basis of this difference,we established a recombinant adenovirus system expressing the S protein from SL-CoV(rAd-Rp3-S)to investigate its immune characterization.Our results showed that immunized mice generated strong humoral immune responses against the SL-CoV S protein.Moreover,a strong cellular immune response demonstrated by elevated IFN-γand IL-6 levels was also observed in these mice.However,the induced antibody from these mice had weaker cross-reaction with the SARS-CoV S protein,and did not neutralize HIV pseudotyped with SARS-CoV S protein.These results demonstrated that the immunogenicity of the SL-CoV S protein is distinct from that of SARS-CoV,which may cause the immunological differences between human SARS-CoV and bat SL-CoV.Furthermore,the recombinant virus could serve as a potential vaccine candidate against bat SL-CoV infection.展开更多
基金supported by the Key Research and Development Program,Ministry of Science and Technology of the People’s Republic of China(Nos.2023YFC2606500,2023YFE0206500).
文摘Coronaviruses are single-stranded,positive-sense RNA enveloped viruses that have posed a significant threat to human health over the past few decades,particularly severe acute respiratory syndrome coronavirus(SARS-CoV),Middle East respiratory syndrome coronavirus(MERS-CoV),and SARS-CoV-2.These viruses have caused widespread infections and fatalities,with profound impacts on global economies,social life,and public health systems.Due to their broad host range in natural settings and the consequent high potential for zoonotic spillover events,a thorough investigation of the common viral mechanisms and the identification of druggable targets for pan-coronavirus antiviral development are of utmost importance.
文摘Since the outbreak of novel coronavirus pneumonia(coronavirus disease 2019,COVID-19),it has rapidly spread to 187 countries,causing serious harm to the health of people and a huge social burden.However,currently,drugs specifically approved for clinical use are not available,except for vaccines against COVID-19 that are being evaluated.Traditional Chinese medicine(TCM)is capable of performing syndrome differentiation and treatment according to the clinical manifestations of patients,and has a better ability of epidemic prevention and control.The authors comprehensively analyzed the etiology and pathogenesis of COVID-19 based on the theory of TCM,and discussed its syndrome differentiation,treatment and prevention measures so as to provide strategies and reference for the prevention and treatment with TCM.
基金supported by the Zhejiang Provincial Natural Science Foundation(LZ22C180002)the Laboratory of Lingnan Modern Agriculture Project(NG2022001)the Zhejiang Provincial Key R&D Program of China(2021C02049)。
文摘Porcine deltacoronavirus(PDCoV)is a swine enteropathogenic CoV that causes severe vomiting,diarrhea and dehydration in suckling piglets,leading to economic losses in the swine industry.There is a great need for a convenient method to detect circulating antibodies and help in accurate diagnosis and disease control.Previously,we demonstrated that a unique PDCoV accessory protein,NS6,is expressed during PDCoV infection in pigs and is incorporated into PDCoV virions;thus,we deduced that NS6 is likely an immunogenic target that can be used for the diagnosis of PDCoV infection.In this study,we first confirmed that NS6 is immunogenic in PDCoV-infected pigs by perform-ing a serum western blot.Furthermore,we developed a novel NS6-based indirect enzyme-linked immunosorbent assay(iELISA)method and compared it to an established S1-based iELISA for the survey of anti-PDCoV IgG or IgA in pigs of different ages in China.The NS6-iELISA has high specificity for the detection of IgG antibodies and no cross-reactivity with other porcine enteric CoVs(transmissible gastroenteritis coronavirus,porcine epidemic diarrhea virus,or swine acute diarrhea syndrome coronavirus).This NS6 serology-based method has great sensitivity and good repeatability,making it a new and cost-saving option for the rapid diagnosis and immunosurveillance of PDCoV,which may also be important for the prevention and control of deltacoronavirus-related infection in pigs and other animals.
文摘Objective:This review aimed to identify the barriers and facilitators to equitable coronavirus disease 2019(COVID-19)vaccine distribution in Nigeria using the consolidated framework for implementation research(CFIR).Methods:A comprehensive search strategy was applied across five databases—Web of Science,MEDLINE,EMBASE,CAB Direct,and CINAHL.The search,conducted as part of a scoping review,yielded 2,751 citations.Seven studies met the inclusion criteria after screening.Data were extracted and analyzed using CFIR constructs to identify key barriers and facilitators to equitable vaccine distribution.Results:Six barriers were identified:limited physical and socioeconomic access,bribery,nepotism,and insufficient availability of translated information.Facilitators included community involvement as local monitoring agents,unannounced staff inspections,healthcare worker training tailored to community needs,and localized outreach strategies such as jingles and call-in programs.CFIR constructs,including Local Conditions,Tailoring Strategies,Available Resources,and Physical Infrastructure,provided a framework for analyzing the findings.Conclusion:This review highlights significant barriers and promising facilitators to equitable vaccine distribution in Nigeria.Targeted interventions,such as community engagement,anti-corruption measures,and culturally tailored strategies,are critical to addressing these challenges and improving access.These findings underscore the need for localized,equity-focused approaches to enhance vaccine distribution systems in Nigeria and other low-resource settings.
文摘BACKGROUND The coronavirus disease 2019(COVID-19)pandemic had a profound societal impact in the United States which was associated with a decrease in overall life expectancy and an increase in substance abuse and firearm injury.Our under-standing of changes in mortality trends during the pandemic and its effect on organ availability for transplantation is limited.AIM To examine the trends of substance abuse and firearm injury fatalities during COVID-19 and a potential correlation with organ transplantation.METHODS Crude rates of population-based deaths among adults(18-75 years)from firearm injury and substance abuse from the period of 2014-2021 were obtained from centers of disease control wide-ranging online data for epidemiologic research database.Crude rates of causes of donor(18-75 years)deaths from 2014-2021 were obtained from the united network for organ sharing database.RESULTS Average annual percentage change(AAPC)deaths among the United States population were 16.4%from substance abuse and 3.4%from firearm injury.AAPC in cause of death among organ donors was 10.9%from drug intoxication and 2.1%from firearm injury.There was a significant(P<0.001)and progressive increase in mortality from both causes during the pandemic(2020-2021)and significant correlation(P<0.001)between population and donor causes of death.COVID-19 exacerbated trends in substance abuse and firearm mortality with a consequent increase in organ donation from donors who died from these two causes.CONCLUSION Identifying the socioeconomic and regional disparities associated with increase in deaths from substance abuse and firearms can help guide post-pandemic healthcare policies and mitigate their impact on organ transplantation.
基金supported by the National Natural Science Foundation of China(grant no.82370015).
文摘The 3CL protease, a highly conserved enzyme in the coronavirus, plays a crucial role in the viral life cycle by facilitating viral replication through precise cleavage of polyproteins. Beyond its proteolytic function, the 3CL protease also engages in intricate interactions with host cell proteins involved in critical cellular processes such as transcription, translation, and nuclear-cytoplasmic transport, effectively hijacking cellular machinery to promote viral replication. Additionally, it disrupts innate immune signaling pathways, suppresses interferon activity and cleaves antiviral proteins. Furthermore, it modulates host cell death pathways including pyroptosis and apoptosis, interferes with autophagy and inhibits stress granule formation to maintain viral infection and exacerbate viral pathogenesis. This review highlights the molecular mechanisms by which the 3CL protease orchestrates virus-host interactions, emphasizing its central role in coronavirus pathogenesis and highlighting potential therapeutic targets for future interventions.
基金funded by the Department of Biotechnology,Ministry of Science and Technology,Government of India(DBT)under grant number ADMaC DBT-NER/LIVS/11/2012.
文摘We report the development of a triplex nucleic acid lateral flow immunoassay(NALFIA)for the detection of the genomes of Nipah virus(NiV),Middle East respiratory syndrome coronavirus(MERS-CoV)and Reston ebolavirus(REBOV),which are intended for screening bats as well as other hosts and reservoirs of these three viruses.Our triplex NALFIA is a two-step assay format:the target nucleic acid in the sample is first amplified using tagged primers,and the tagged dsDNA amplicons are captured by antibodies immobilized on the NALFIA device,resulting in signal development from the binding of a streptavidin-colloidal gold conjugate to a biotin tag on the captured amplicons.Triplex amplification of the N gene of NiV,the UpE gene of MERS-CoV,and the Vp40 gene of REBOV was optimized,and three compatible combinations of hapten labels and antibodies were identified for end point detection.The lowest RNA copy numbers detected by the triplex NALFIA were 8.21e4 for the NiV N target,7.09e1 for the MERS-CoV UpE target,and 1.83e4 for the REBOV Vp40 target.Using simulated samples,the sensitivity and specificity for MERS-CoV and REBOV targets were estimated to be 100%,while the sensitivity and specificity for the NiV target were 91%and 93.3%,respectively.The compliance rate between triplex NALFIA and real-time RT‒PCR was 92%for the NiV N target and 100%for the MERS-CoV UpE and REBOV Vp40 targets.
文摘The current corona virus disease 2019 outbreak caused by severe acute respiratory syndrome coronavirus 2 started in Wuhan,China in December 2019 and has put the world on alert.To safeguard Chinese citizens and to strengthen global health security,China has made great efforts to control the epidemic.Many in the global community have joined China to limit the epidemic.However,discrimination and prejudice driven by fear or misinformation have been flowing globally,superseding evidence and jeopardizing the anti-severe acute respiratory syndrome coronavirus 2 efforts.We analyze this phenomenon and its underlying causes and suggest practical solutions.
文摘The effects of coronaviruses on the respiratory system are of great concern,but their effects on the digestive system receive much less attention.Coronaviruses that infect mammals have shown gastrointestinal pathogenicity and caused symptoms such as diarrhea and vomiting.Available data have shown that human coronaviruses,including the newly emerged SARS-CoV-2,mainly infect the respiratory system and cause symptoms such as cough and fever,while they may generate gastrointestinal symptoms.However,there is little about the relation between coronavirus and digestive system.This review specifically addresses the effects of mammalian and human coronaviruses,including SARS-CoV-2,on the digestive tract,helping to cope with the new virus infection-induced disease,COVID-19.
基金the National Science and Technology Major Project of China(No.2018ZX10302206-003)the Zhejiang Provincial Natural Science Foundation of China(No.LY16H160057)+1 种基金the Health Commission of Zhejiang Province(No.2016KYA162)the Zhejiang Provincial Science and Technology Project of Traditional Chinese Medicine of China(No.2015ZA026)。
文摘Although the coronavirus disease 2019(COVID-19)epidemic is still ongoing,vaccination rates are rising slowly and related treatments and drugs are being developed.At the same time,there is increasing evidence of preexisting immunity against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)in humans,mainly consisting of preexisting antibodies and immune cells(including T cells and B cells).The presence of these antibodies is mainly due to the seasonal prevalence of four common coronavirus types,especially OC43 and HKU1.The accumulated relevant evidence has suggested that the target of antibodies is mainly the S2 subunit of S protein,followed by evolutionary conservative regions such as the nucleocapsid(N)protein.Additionally,preexisting memory T and B cells are also present in the population.Preexisting antibodies can help the body protect against SARS-CoV-2 infection,reduce the severity of COVID-19,and rapidly increase the immune response post-infection.These multiple effects can directly affect disease progression and even the likelihood of death in certain individuals.Besides the positive effects,preexisting immunity may also have negative consequences,such as antibody-dependent enhancement(ADE)and original antigenic sin(OAS),the prevalence of which needs to be further established.In the future,more research should be focused on evaluating the role of preexisting immunity in COVID-19 outcomes,adopting appropriate policies and strategies for fighting the pandemic,and vaccine development that considers preexisting immunity.
基金The reported study was funded by RFBR,project number 20-04-60051.
文摘Objective:To investigate the genetic diversity of coronaviruses in wild and domestic birds in the bird park and live poultry markets of Ca Mau province in Vietnam in 2020.Methods:A total of 228 samples(121 from wild birds and 107 from poultry)were collected in the territory of Ca Mau province of Vietnam in 2020.The avian samples were tested for the presence of the four genera of coronaviruses using reverse transcription and nested PCR.Molecular genetic analysis using targeted NGS sequencing of RdRp gene was performed for 29 representative samples(12 samples from wild birds and 17 from poultry).Phylogenetic analysis was performed using the neighbour joininig method with 1000 bootstrap replications using MEGA X software.Results:Among wild birds,21.5%samples were positive for the genetic material of coronaviruses and 38.3%samples were positive for coronaviruses among poultry.Genetic analysis of the partial sequence of RdRp gene from representative samples revealed that wild birds were carriers of gammacoronaviruses and deltacoronaviruses.Among poultry,three genotypes of infectious bronchitis virus(QX,Mass and Q1)were detected in chickens,with QX genotypes being predominant,and viruses of DCoV group were detected in domestic ducks.There was no detection of alphacoronaviruses or betacoronaviruses in the studied birds.Conclusions:Coronaviruses of genera Gammacoronavirus and Deltacoronavirus were detected in wild birds.A high percentage of infectious bronchitis virus was detected in poultry.Thus,there is a need for broader surveillance of coronaviruses in birds,which can be used for evaluation of diversity,evolution and distribution of coronaviruses in Vietnam.Continuous surveillance of coronaviruses circulation in wild and domestic animals is necessary for implementing strategic measures for poultry and domestic animal protection and for evaluation of possible risk of circulating coronaviruses to human health.
基金This research was supported by National Science Founda-tion of China (No. 30000123) and Conversation Department of Wildlife Ani-mal & Plants of State Forestry Bureau.
文摘In order to survey the infectious situation of canine coronavirus (CCV) in giant panda population, a virus neutralization test detecting specific antibodies against CCV in giant panda抯 sera was established by using two-fold dilutions of serum and 100 TCID50 of the virus. The 62 sera samples of giant pandas, which were gathered from zoos and reserve region of Sichuan Province, China were detected. The neutralization antibody titer of 1:4 was recognized as the positive criterion, 8 sera samples were detected to be positive, and the positive rate was 12.9%. The titers of neutralizing antibody ranged from 1:8 to 1:32. It was the first comprehensive investigation on neutralization antibodies against CCV in giant panda population in China. The results of study showed that the infection of CCV in giant panda population was universal, which has posed a threat to the health of giant panda. Therefore, it is incumbent on us to study safe and effective vaccines to protect giant panda against CCV infection.
基金the TCM research project of Health Commission of Hubei Province(No.ZY2019Q005)。
文摘The novel coronavirus pneumonia broke out in 2019 and spread rapidly. In 30 different countries, there are over seventy thousand patients have been diagnosed in total. Therefore, it is urgent to develop the effective program to prevent and treat for the novel coronavirus pneumonia. In view of Traditional Chinese Medicine has accumulated a solid theoretical foundation of plague in ancient and recent decades. Meanwhile, Traditional Chinese Medicine can provide the more effective and personalized treatment via adjusting the specific medicine for each patient based on the different syndromes. In addition, TCM often has different effect on the distinct stages of diseases, contributing to the prevention, treatment and rehabilitation. Nowadays, TCM has exhibited decent effect in the in the fight against NCP. Therefore, it is convinced that Traditional Chinese Medicine is an effective treatment for 2019 novel coronavirus pneumonia.
文摘prevalence.A number of clinical workers and researchers have made great efforts to understand the pathogenesis and clinical characteristics and develop effective drugs for treatment.However,no effective drugs with antiviral effects on severe acute respiratory syndrome coronavirus 2 have been discovered currently.Traditional Chinese medicine(TCM)has gained abundant experience in the treatment of infectious diseases for thousands of years.In this review,the authors summarized the clinical outcome,pathogensis and current application of TCM on coronavirus disease 2019.Further,we discussed the potential mechanisms and the future research directions of TCM against severe acute respiratory syndrome coronavirus 2.
基金the National Key R&D Pro-gram of China(2019YFC1200501)Research Units of Discovery of Un-known Bacteria and Function(2018RU010)the Golden Seed Program of Beijing Chaoyang Hospital(CYJZ202220).
文摘The current pandemic of COVID-19 caused by a novel coronavirus,severe acute respiratory syndrome coronavirus-2(SARS-CoV-2),threatens human health around the world.Of particular concern is that bats are recognized as one of the most potential natural hosts of SARS-CoV-2;however,coronavirus ecology in bats is still nascent.Here,we performed a degenerate primer screening and next-generation sequencing analysis of 112 bats,collected from Hainan Province,China.Three coronaviruses,namely bat betacoronavirus(Bat CoV)CD35,Bat CoV CD36 and bat alpha-coronavirus CD30 were identified.Bat CoV CD35 genome had 99.5%identity with Bat CoV CD36,both sharing the highest nucleotide identity with Bat Hp-betacoronavirus Zhejiang2013(71.4%),followed by SARS-CoV-2(54.0%).Phylogenetic analysis indicated that Bat CoV CD35 formed a distinct clade,and together with Bat Hp-betacoronavirus Zhejiang2013,was basal to the lineage of SARS-CoV-1 and SARS-CoV-2.Notably,Bat CoV CD35 harbored a canonical furin-like S1/S2 cleavage site that resembles the corresponding sites of SARS-CoV-2.The furin cleavage sites between CD35 and CD36 are identical.In addition,the receptor-binding domain of Bat CoV CD35 showed a highly similar structure to that of SARS-CoV-1 and SARS-CoV-2,especially in one binding loop.In conclusion,this study deepens our understanding of the diversity of coronaviruses and provides clues about the natural origin of the furin cleavage site of SARS-CoV-2.
文摘BACKGROUND: The study aims to illustrate the clinical characteristics and development of septic shock in intensive care unit(ICU) patients confirmed with severe acute respiratory syndrome coronavirus 2(SARS-Co V-2) infection, and to perform a comprehensive analysis of the association between septic shock and clinical outcomes in critically ill patients with coronavirus disease(COVID-19).METHODS: Patients confirmed with SARS-Co V-2 infection, who were admitted to the ICU of the Third People's Hospital of Shenzhen from January 1 to February 7, 2020, were enrolled. Clinical characteristics and outcomes were compared between patients with and without septic shock.RESULTS: In this study, 35 critically ill patients with COVID-19 were included. Among them, the median age was 64 years(interquartile range [IQR] 59-67 years), and 10(28.4%) patients were female. The median ICU length of stay was 16 days(IQR 8-23 days). Three(8.6%) patients died during hospitalization. Nine(25.7%) patients developed septic shock in the ICU, and these patients had a significantly higher incidence of organ dysfunction and a worse prognosis than patients without septic shock.CONCLUSIONS: Septic shock is associated with a poor outcome in critically ill COVID-19 patients and is one of the hallmarks of the severity of patients receiving ICU care. A dysregulated immune response, uncontrolled infl ammation, and coagulation disorders are strongly associated with the development and progression of COVID-19-related septic shock.
基金supported by the National Clinical Research Center for Infectious DiseasesFunds for the Construction of Key Medical Disciplines in Shenzhen and the Sanming Project of Medicine in Shenzhen[SZSM201612014]。
文摘Objective Here we aimed to investigate the difference in clinical characteristics and outcomes between pediatric and adult patients with COVID-19.Methods A total of 333 consecutive patients with laboratory-confirmed SARS-CoV-2 infection treated in the departments of Internal medicine of Shenzhen Third People’s Hospital from January 11 th to February 10 th,2020 were included.The data were obtained from electronic medical records.The epidemiological data,clinical characteristics,length of hospital stays,and outcomes of pediatric and adult patients were compared.Results Compared with adult patients,pediatric patients had a shorter time of symptom onset to hospitalization than adults[median time,1(IQR,1.0-1.0)d vs.3(IQR,2.0-6.0)d,P<0.001],milder or fewer symptoms,less severe chest CT findings.The clinical severity classification of children was less severe than adults.Up to 15 th March,the end of the follow-up,33(100%)children and 292(97.3%)adult patients had been discharged from hospital.Only 2(0.7%)adult patients died,with an overall case mortality of 0.6%.The median length of hospital stay of pediatric patients was shorter than that of adult patients[19(95%CI:16.6-21.4)d vs.21(95%CI:19.9-22.1)d,P=0.024].Conclusion Pediatric patients with COVID-19 had milder or less clinical symptoms,less evident pulmonary imaging changes,better prognosis,and shorter length of hospital stay.
基金Supported by the Zhejiang Natural Science Foundation of China,No.LGF18H030009.
文摘BACKGROUND Since December 2019,there have been many new cases of coronavirus pneumonia in Wuhan,Hubei Province,which has gradually spread throughout the country.AIM To explore our hospital’s innovative management system to ensure the efficient operation of fever clinics during the epidemic,since controlling the spread of disease is an important way to prevent and control the epidemic.METHODS In total,200 outpatients with fever at our hospital between November 2019 and July 2020 were selected and allocated into two groups.RESULTS The fever clinic in our hospital operated smoothly,and infection with the novel coronavirus disease(COVID-19)has not been reported in our hospital.Additionally,we did not have any cases of missed diagnosis.The awareness regarding COVID-19 infection sources,transmission routes,early symptoms,and preventive measures was significantly higher in our fever clinic than in those of the pre-management group.CONCLUSION"An integrated system,three separate responsibilities"ensured the efficient functioning of our fever outpatient clinic and early screening of COVID-19 cases,which effectively curbed the transmission of COVID-19 and hence prevented COVID-19 pneumonia epidemic in our hospital,ultimately achieving the maximum effect of epidemic prevention and control.
文摘The synonymous codon usage in the translational initiation and termination regions of genes of severe acute respiratory syndrome (SARS) coronavirus and five other viruses in Coronaviridae was systematically analyzed.The results indicate that most minor codons for these coronaviruses are preferentially used in the initial and terminal region.The minor codons preferentially used in the initial region are thought to have a negative effect on gene expression,which can be explained by the minor codon modulator hypothesis.It also indicates that the minor codons preferentially used in the terminal region may regulate the level of gene expression.The proposed results strongly imply that the minor codon modulator hypothesis can be applied to both some bacteria and some viruses.
基金supported by the State Key Program for Basic Research Grant(2005CB523004)from the Chinese Ministry of Science and Technologythe Knowledge Innovation Program Key Project administered by the Chinese Academy of Sciences(KSCX1-YW-R-07)
文摘A group of SARS-like coronaviruses(SL-CoV)have been identified in horseshoe bats.Despite SL-CoVs and SARS-CoV share identical genome structure and high-level sequence similarity,SL-CoV does not bind to the same cellular receptor as for SARS-CoV and the N-terminus of the S proteins only share 64%amino acid identity,suggesting there are fundamental differences between these two groups of coronaviruses.To gain insight into the basis of this difference,we established a recombinant adenovirus system expressing the S protein from SL-CoV(rAd-Rp3-S)to investigate its immune characterization.Our results showed that immunized mice generated strong humoral immune responses against the SL-CoV S protein.Moreover,a strong cellular immune response demonstrated by elevated IFN-γand IL-6 levels was also observed in these mice.However,the induced antibody from these mice had weaker cross-reaction with the SARS-CoV S protein,and did not neutralize HIV pseudotyped with SARS-CoV S protein.These results demonstrated that the immunogenicity of the SL-CoV S protein is distinct from that of SARS-CoV,which may cause the immunological differences between human SARS-CoV and bat SL-CoV.Furthermore,the recombinant virus could serve as a potential vaccine candidate against bat SL-CoV infection.
