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
The recent outbreak of coronavirus disease(COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has already affected a large population of the world. SARS-CoV-2 belongs to the same...The recent outbreak of coronavirus disease(COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has already affected a large population of the world. SARS-CoV-2 belongs to the same family of severe acute respiratory syndrome coronavirus(SARS-CoV) and Middle East respiratory syndrome coronavirus(MERSCoV). COVID-19 has a complex pathology involving severe acute respiratory infection, hyper-immune response, and coagulopathy. At present, there is no therapeutic drug or vaccine approved for the disease. There is an urgent need for an ideal animal model that can reflect clinical symptoms and underlying etiopathogenesis similar to COVID-19 patients which can be further used for evaluation of underlying mechanisms, potential vaccines, and therapeutic strategies. The current review provides a paramount insight into the available animal models of SARS-CoV-2, SARS-CoV, and MERS-CoV for the management of the diseases.展开更多
In humans, infection with the coronavirus, especially the severe acute respiratory syndrome coronavirus(SARS-CoV) and the emerging Middle East respiratory syndrome coronavirus(MERS-CoV), induces acute respiratory fail...In humans, infection with the coronavirus, especially the severe acute respiratory syndrome coronavirus(SARS-CoV) and the emerging Middle East respiratory syndrome coronavirus(MERS-CoV), induces acute respiratory failure, resulting in high mortality. Irregular coronavirus related epidemics indicate that the evolutionary origins of these two pathogens need to be identified urgently and there are still questions related to suitable laboratory animal models. Thus, in this review we aim to highlight key discoveries concerning the animal origin of the virus and summarize and compare current animal models.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
An acute respiratory illness caused by a novel coronavirus,namely,severe acute respiratory syndrome coronavirus 2,the virus that causes coro-navirus disease 2019(COVID-19),began spreading across China in late December...An acute respiratory illness caused by a novel coronavirus,namely,severe acute respiratory syndrome coronavirus 2,the virus that causes coro-navirus disease 2019(COVID-19),began spreading across China in late December 2019.The disease gained global attention as it spread worldwide.Since the COVID-19 pandemic began,many studies have focused on the impact of the disease on conditions such as diabetes,cardiovascular disease,pulmonary disorders,and renal malfunction.However,few studies have focused on musculoskeletal disorders related to COVID-19 infection.In this review,we update the current knowledge on the coronavirus with special reference to its effects during and after the pandemic on musculoskeletal aliments,which may inform clinical practice.展开更多
Like RNA viruses in general,coronaviruses(CoV)exhibit high mutation rates which,in combination with their strong tendency to recombine,enable them to overcome the host species barrier and adapt to new hosts.It is curr...Like RNA viruses in general,coronaviruses(CoV)exhibit high mutation rates which,in combination with their strong tendency to recombine,enable them to overcome the host species barrier and adapt to new hosts.It is currently known that six CoV are able to infect pigs.Four of them belong to the genus Alphacoronavirus[transmissible gastroenteritis coronavirus(TEGV),porcine respiratory coronavirus(PRCV),porcine epidemic diarrhea virus(PEDV),swine acute diarrhea syndrome coronavirus(SADS-CoV)],one of them to the genus Betacoronavirus[porcine hemagglutinating encephalomyelitis virus(PHEV)]and the last one to the genus Deltacoronavirus(PDCoV).PHEV was one of the first identified swine CoV and is still widespread,causing subclinical infections in pigs in several countries.PRCV,a spike deletion mutant of TGEV associated with respiratory tract infection,appeared in the 1980 s.PRCV is considered nonpathogenic since its infection course is mild or subclinical.Since its appearance,pig populations have become immune to both PRCV and TGEV,leading to a significant reduction in the clinical and economic importance of TGEV.TGEV,PEDV and PDCoV are enteropathogenic CoV and cause clinically indistinguishable acute gastroenteritis in all age groups of pigs.PDCoV and SADS-CoV have emerged in 2014(US)and in 2017(China),respectively.Rapid diagnosis is crucial for controlling CoV infections and preventing them from spreading.Since vaccines are available only for some porcine CoV,prevention should focus mainly on a high level of biosecurity.In view of the diversity of CoV and the potential risk factors associated with zoonotic emergence,updating the knowledge concerning this area is essential.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a highly contagious virus that can transmit through respiratory droplets,aerosols,or contacts.Frequent touching of contaminated surfaces in public areas is...Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a highly contagious virus that can transmit through respiratory droplets,aerosols,or contacts.Frequent touching of contaminated surfaces in public areas is therefore a potential route of SARS-CoV-2 transmission.The inanimate surfaces have often been described as a source of nosocomial infections.However,summaries on the transmissibility of coronaviruses from contaminated surfaces to induce the coronavirus disease 2019 are rare at present.This review aims to summarize data on the persistence of different coronaviruses on inanimate surfaces.The literature was systematically searched on Medline without language restrictions.All reports with experimental evidence on the duration persistence of coronaviruses on any type of surface were included.Most viruses from the respiratory tract,such as coronaviruses,influenza,SARS-CoV,or rhinovirus,can persist on surfaces for a few days.Persistence time on inanimate surfaces varied from minutes to up to one month,depending on the environmental conditions.SARSCoV-2 can be sustained in air in closed unventilated buses for at least 30 min without losing infectivity.The most common coronaviruses may well survive or persist on surfaces for up to one month.Viruses in respiratory or fecal specimens can maintain infectivity for quite a long time at room temperature.Absorbent materials like cotton are safer than unabsorbent materials for protection from virus infection.The risk of transmission via touching contaminated paper is low.Preventive strategies such as washing hands and wearing masks are critical to the control of coronavirus disease 2019.展开更多
Outbreaks of severe virus infections with the potential to cause global pandemics are increasingly concerning.One type of those commonly emerging and re-emerging pathogens are coronaviruses(SARS-Co V,MERS-Co V and SAR...Outbreaks of severe virus infections with the potential to cause global pandemics are increasingly concerning.One type of those commonly emerging and re-emerging pathogens are coronaviruses(SARS-Co V,MERS-Co V and SARS-Co V-2).Wild animals are hosts of different coronaviruses with the potential risk of cross-species transmission.However,little is known about the reservoir and host of coronaviruses in wild animals in Qinghai Province,where has the greatest biodiversity among the world's high-altitude regions.Here,from the next-generation sequencing data,we obtained a known beta-coronavirus(beta-Co V)genome and a novel delta-coronavirus(delta-Co V)genome from faecal samples of 29 marmots,50 rats and 25 birds in Yushu Tibetan Autonomous Prefecture,Qinghai Province,China in July 2019.According to the phylogenetic analysis,the beta-Co V shared high nucleotide identity with Coronavirus HKU24.Although the novel delta-Co V(Mt Co V)was closely related to Sparrow deltacoronavirus ISU42824,the protein spike of the novel delta-Co V showed highest amino acid identity to Sparrow coronavirus HKU17(73.1%).Interestingly,our results identified a novel host(Montifringilla taczanowskii)for the novel delta-Co V and the potential cross-species transmission.The most recent common ancestor(t MRCA)of Mt Co Vs along with other closest members of the species of Coronavirus HKU15 was estimated to be 289 years ago.Thus,this study increases our understanding of the genetic diversity of beta-Co Vs and deltaCo Vs,and also provides a new perspective of the coronavirus hosts.展开更多
Although coronavirus(CoV)infection is often characterized by respiratory symptoms,the virus can also result in extrapulmonary symptoms,especially the symptoms related to the digestive system.The outbreak of coronaviru...Although coronavirus(CoV)infection is often characterized by respiratory symptoms,the virus can also result in extrapulmonary symptoms,especially the symptoms related to the digestive system.The outbreak of coronavirus disease 2019(COVID-19)is currently the world’s most pressing public health threat and has a significant impact on civil societies and the global economy.The occurrence of digestive symptoms in patients with COVID-19 is closely related to the development and prognosis of the disease.Moreover,thus far,there are no specific antiviral drug or vaccine approved for the treatment or prevention of COVID-19.Therefore,we elaborate on the effects of CoVs on the digestive system and the potential underlying mechanisms.展开更多
Since the 2002–2003 severe acute respiratory syndrome(SARS) outbreak prompted a search for the natural reservoir of the SARS coronavirus, numerous alpha- and betacoronaviruses have been discovered in bats around the ...Since the 2002–2003 severe acute respiratory syndrome(SARS) outbreak prompted a search for the natural reservoir of the SARS coronavirus, numerous alpha- and betacoronaviruses have been discovered in bats around the world. Bats are likely the natural reservoir of alpha- and betacoronaviruses, and due to the rich diversity and global distribution of bats, the number of bat coronaviruses will likely increase. We conducted a surveillance of coronaviruses in bats in an abandoned mineshaft in Mojiang County, Yunnan Province, China, from 2012–2013. Six bat species were frequently detected in the cave: Rhinolophus sinicus, Rhinolophus affinis, Hipposideros pomona, Miniopterus schreibersii, Miniopterus fuliginosus, and Miniopterus fuscus. By sequencing PCR products of the coronavirus RNA-dependent RNA polymerase gene(Rd Rp), we found a high frequency of infection by a diverse group of coronaviruses in different bat species in the mineshaft. Sequenced partial Rd Rp fragments had 80%–99% nucleic acid sequence identity with well-characterized Alphacoronavirus species, including Bt CoV HKU2, Bt CoV HKU8, and Bt CoV1,and unassigned species Bt CoV HKU7 and Bt CoV HKU10. Additionally, the surveillance identified two unclassified betacoronaviruses, one new strain of SARS-like coronavirus, and one potentially new betacoronavirus species. Furthermore, coronavirus co-infection was detected in all six bat species, a phenomenon that fosters recombination and promotes the emergence of novel virus strains. Our findings highlight the importance of bats as natural reservoirs of coronaviruses and the potentially zoonotic source of viral pathogens.展开更多
The outbreak of the COVID-19 epidemic in 2020 has caused unprecedented panic among all mankind,pointing the major importance of effective treatment.Since the emergence of the swine acute diarrhea syndrome coronavirus(...The outbreak of the COVID-19 epidemic in 2020 has caused unprecedented panic among all mankind,pointing the major importance of effective treatment.Since the emergence of the swine acute diarrhea syndrome coronavirus(SADS-CoV)at the end of 2017,multiple reports have indicated that the bat-related SADS-CoV possesses a potential threat for cross-species transmission.Vaccines and antiviral drugs development deserve more attention.In this study,we found that the HER2 phosphorylation inhibitor(CP-724714)inhibited SADS-CoV infection in a dose-dependent manner.Further validation demonstrated that CP-724714 affected at the post-entry stage of SADS-CoV infection cycle.Also,efficient SADS-CoV infection required the activation of HER2 and its cascade Ras-Raf-Mek-Erk signaling pathway.In addition,CP-724714 has a broad-spectrum anti-swine diarrhea coronaviruses activity,and can dose-dependently combat SADS-CoV,porcine epidemic diarrhea virus(PEDV),porcine deltacoronavirus(PDCoV)and transmissible gastroenteritis virus(TGEV)infection in vitro with a specificity index of greater than 21.98,9.38,95.23 and 31.62,respectively.These results highlight the potential utility of CP-724714 or antiviral drugs targeting with HER2 and its cascade Ras-Raf-Mek-Erk signaling pathway as host-targeted SADS-CoV and other related coronaviruses therapeutics.展开更多
New coronavirus referred to SARS-CoV-2 has caused a worldwide pandemic(COVID-19)declared by WHO.Coronavirus disease 2019(COVID-19)is an infectious disease with severe acute respiratory syndrome caused by coronavirus-2...New coronavirus referred to SARS-CoV-2 has caused a worldwide pandemic(COVID-19)declared by WHO.Coronavirus disease 2019(COVID-19)is an infectious disease with severe acute respiratory syndrome caused by coronavirus-2(SARS-CoV-2).SARS-CoV-2 is akin to SARS-CoV,which was the causative agent of severe acute respiratory syndrome(SARS)in 2002 as well as to that of Middle East respiratory syndrome(MERS)in 2012.SARS-CoV-2 has been revealed to belong to Coronaviridiae family as a member ofβ-coronaviruses.It has a positive-sense single-stranded RNA with the largest RNA genome.Since its genomic sequence has a notable similarity to that of SARS-CoV,antiviral drugs used to treat SARS and MERS are now being also applied for COVID-19 treatment.In order to combat SARS-CoV-2,many drug and vaccine development studies at experimental and clinical levels are currently conducted worldwide.In this sense,medicinal plants and the pure natural molecules isolated from plants have been reported to exhibit significant inhibitory antiviral activity against SARS-CoV and other types of coronaviruses.In the present review,plant extracts and natural molecules with the mentioned activity are discussed in order to give inspiration to researchers to take these molecules into consideration against SARS-CoV-2.展开更多
Dear Editor,The 2002–2003 severe acute respiratory syndrome coronavirus（SARS-CoV）（Drosten et al.,2003）caused human pandemics that began in China and spread globally.Subsequently,
In this paper, we report a multiple sequence alignment result on the basis of 10 amino acid sequences of the M protein, which come from different coronaviruses (4 SARS associated and 6 others known). The alignment mo...In this paper, we report a multiple sequence alignment result on the basis of 10 amino acid sequences of the M protein, which come from different coronaviruses (4 SARS associated and 6 others known). The alignment model was based on the profile HMM (Hidden Markov Model), and the model training was implemented through the SAHMM (Self Adapting Hidden Markov Model) software developed by the authors.展开更多
The surface glycoproteins of coronaviruses play an important role in receptor binding and cell entry. Different coronaviruses interact with their specific receptors to enter host cells. Lentiviruses pseudotyped with t...The surface glycoproteins of coronaviruses play an important role in receptor binding and cell entry. Different coronaviruses interact with their specific receptors to enter host cells. Lentiviruses pseudotyped with their spike proteins(S) were compared to analyze the entry efficiency of various coronaviruses. Our results indicated that S proteins from different coronaviruses displayed varied abilities to mediate pseudotyped virus infection. Furthermore, the cell tropisms of porcine epidemic diarrhea virus(PEDV) and transmissible gastroenteritis virus(TGEV) have been characterized by live and pseudotyped viruses. Both live and pseudoviruses could infected VeroCCL-81(monkey kidney), Huh-7(human liver), and PK-15(pig kidney) cells efficiently. CCL94(cat kidney) cells could be infected efficiently by TGEV but not PEDV. Overall, our study provides new insights into the mechanisms of viral entry and forms a basis for antiviral drug screening.展开更多
The frequent emergence of coronavirus(CoV)epidemics has seriously threatened public health and stock farming.The major hosts for CoVs are birds and mammals.Although most CoVs inhabit their specific natural hosts,some ...The frequent emergence of coronavirus(CoV)epidemics has seriously threatened public health and stock farming.The major hosts for CoVs are birds and mammals.Although most CoVs inhabit their specific natural hosts,some may occasionally cross the host barrier to infect livestock and even people,causing a variety of diseases.Since the beginning of the new century,increasing attention has been given to research on CoVs due to the emergence of highly pathogenic and genetically diverse CoVs that have caused several epidemics,including the recent COVID-19 pandemic.CoVs belong to the Coronaviridae family of the Nidovirales order.Recently,advanced techniques for viral detection and viral genome analyses have enabled characterization of many new nidoviruses than ever and have greatly expanded the Nidovirales order with new classification and nomenclature.Here,we first provide an overview of the latest research progress in the classification of the Nidovirales order and then introduce the host range,genetic variation,genomic pattern and pathogenic features of epidemic CoVs and other epidemic viruses.This information will promote understanding of the phylogenetic relationship and infectious transmission of various pathogenic nidoviruses,including epidemic CoVs,which will benefit virological research and viral disease control.展开更多
Bats are the natural reservoir hosts for SARS-related coronavirus(SARSr-CoV)and other highly pathogenic microorganisms.Therefore,it is conceivable that an individual bat may harbor multiple microbes.However,there is l...Bats are the natural reservoir hosts for SARS-related coronavirus(SARSr-CoV)and other highly pathogenic microorganisms.Therefore,it is conceivable that an individual bat may harbor multiple microbes.However,there is limited knowledge on the overall co-circulation of microorganisms in bats.Here,we conducted a 16-year monitoring of bat viruses in south and central China and identified 238 SARSr-CoV positive samples across nine bat species from ten provinces or administrative districts.Among these,76 individual samples were selected for further metagenomics analysis.We found a complex microenvironment characterized by the general cocirculation of microbes from two different sources:mammal-associated viruses or environment-associated microbes.The later includes commensal bacteria,enterobacteria-related phages,and insect or fungal viruses of food origin.Results showed that 25%(19/76)of the samples contained at least one another mammal-associated virus,notably alphacoronaviruses(13/76)such as AlphaCoV/YN2012,HKU2-related CoV and AlphaCoV/Rf-HuB2013,along with viruses from other families.Notably,we observed three viruses co-circulating within a single bat,comprising two coronavirus species and one picornavirus.Our analysis also revealed the potential presence of pathogenic bacteria or fungi in bats.Furthermore,we obtained 25 viral genomes from the 76 bat SARSr-CoV positive samples,some of which formed new evolutionary lineages.Collectively,our study reveals the complex microenvironment of bat microbiome,facilitating deeper investigations into their pathogenic potential and the likelihood of cross-species transmission.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
Zoonotic transmissions of emerging pathogens from wildlife to human have shaped the history of mankind. These events have also highlighted our poor understanding of microorganisms circulated in wild animals. Coronavir...Zoonotic transmissions of emerging pathogens from wildlife to human have shaped the history of mankind. These events have also highlighted our poor understanding of microorganisms circulated in wild animals. Coronaviruses and astroviruses,which can be found from a wide range of mammals,were recently detected in bats. Strikingly,these bat viruses are genetically highly diverse and these interesting findings might help to better understand the evolution and ecology of these viruses. The discoveries of these novel bats viruses not only suggested that bats are important hosts for these virus families,but also reiterated the role of bats as a reservoir of viruses that might pose a zoonotic threat to human health.展开更多
BACKGROUND Ribavirin is a broad-spectrum nucleoside antiviral drug with multimodal mechanisms of action,which supports its longevity and quality as a clinical resource.It has been widely administered for measles and c...BACKGROUND Ribavirin is a broad-spectrum nucleoside antiviral drug with multimodal mechanisms of action,which supports its longevity and quality as a clinical resource.It has been widely administered for measles and coronavirus infections.Despite the large amount of data concerning the use of ribavirin alone or in combination for measles,severe acute respiratory syndrome,Middle East respiratory syndrome,and coronavirus disease 2019(COVID-19)outbreaks,the conclusions of these studies have been contradictory.Underlying reasons for these discrepancies include possible study design inaccuracies and failures and misinterpretations of data,and these potential confounds should be addressed.AIM To determine the confounding factors of ribavirin treatment studies and propose a therapeutic scheme for COVID-19.METHODS PubMed database was searched over a period of five decades utilizing the terms“ribavirin”alone or combined with other compounds in measles,severe acute respiratory syndrome,Middle East respiratory syndrome,and COVID-19 infections.The literature search was performed and described according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Articles were considered eligible when they reported on ribavirin dose regimens and/or specified outcomes concerning its efficacy and/or possible adverseeffects.In vitro and animal studies were also retrieved.A chapter on ribavirin’s pharmacology was included as well.RESULTS In addition to the difficulties and pressures of an emerging pandemic,there is the burden of designing and conducting well-organized,double-blind,randomized controlled trials.Many studies have succumbed to specific pitfalls,one of which was identified in naturally ribavirin-resistant Vero cell lines in in vitro studies.Other pitfalls include study design inconsistent with the well-established clinical course of disease;inappropriate pharmacology of applied treatments;and the misinterpretation of study results with misconceived generalizations.A comprehensive treatment for COVID-19 is proposed,documented by thorough,longterm investigation of ribavirin regimens in coronavirus infections.CONCLUSION A comprehensive treatment strictly tailored to distinct disease stages was proposed based upon studies on ribavirin and coronavirus infections.展开更多
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.
文摘The recent outbreak of coronavirus disease(COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has already affected a large population of the world. SARS-CoV-2 belongs to the same family of severe acute respiratory syndrome coronavirus(SARS-CoV) and Middle East respiratory syndrome coronavirus(MERSCoV). COVID-19 has a complex pathology involving severe acute respiratory infection, hyper-immune response, and coagulopathy. At present, there is no therapeutic drug or vaccine approved for the disease. There is an urgent need for an ideal animal model that can reflect clinical symptoms and underlying etiopathogenesis similar to COVID-19 patients which can be further used for evaluation of underlying mechanisms, potential vaccines, and therapeutic strategies. The current review provides a paramount insight into the available animal models of SARS-CoV-2, SARS-CoV, and MERS-CoV for the management of the diseases.
基金National Key Research and Development Project of China,Grant/Award Number:2016YFD0500304CAMS Innovation Fund for Medical Sciences,Grant/Award Number:NO.2016-I2M-1-014\2016-12M-006the Chinese National Major S&T Project,Grant/Award Number:NO.2017ZX10304402-001-003
文摘In humans, infection with the coronavirus, especially the severe acute respiratory syndrome coronavirus(SARS-CoV) and the emerging Middle East respiratory syndrome coronavirus(MERS-CoV), induces acute respiratory failure, resulting in high mortality. Irregular coronavirus related epidemics indicate that the evolutionary origins of these two pathogens need to be identified urgently and there are still questions related to suitable laboratory animal models. Thus, in this review we aim to highlight key discoveries concerning the animal origin of the virus and summarize and compare current animal models.
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.
文摘An acute respiratory illness caused by a novel coronavirus,namely,severe acute respiratory syndrome coronavirus 2,the virus that causes coro-navirus disease 2019(COVID-19),began spreading across China in late December 2019.The disease gained global attention as it spread worldwide.Since the COVID-19 pandemic began,many studies have focused on the impact of the disease on conditions such as diabetes,cardiovascular disease,pulmonary disorders,and renal malfunction.However,few studies have focused on musculoskeletal disorders related to COVID-19 infection.In this review,we update the current knowledge on the coronavirus with special reference to its effects during and after the pandemic on musculoskeletal aliments,which may inform clinical practice.
基金supported by the National Science Centre,Poland,under research project(DEC-2014/13/B/NZ6/02566)statutory funding 506.514.05.00 of the Department of Preclinical Sciences and Infectious Diseases,Faculty of Veterinary Medicine and Animal Science,Poznan University of Life Sciences,Poznan,Poland。
文摘Like RNA viruses in general,coronaviruses(CoV)exhibit high mutation rates which,in combination with their strong tendency to recombine,enable them to overcome the host species barrier and adapt to new hosts.It is currently known that six CoV are able to infect pigs.Four of them belong to the genus Alphacoronavirus[transmissible gastroenteritis coronavirus(TEGV),porcine respiratory coronavirus(PRCV),porcine epidemic diarrhea virus(PEDV),swine acute diarrhea syndrome coronavirus(SADS-CoV)],one of them to the genus Betacoronavirus[porcine hemagglutinating encephalomyelitis virus(PHEV)]and the last one to the genus Deltacoronavirus(PDCoV).PHEV was one of the first identified swine CoV and is still widespread,causing subclinical infections in pigs in several countries.PRCV,a spike deletion mutant of TGEV associated with respiratory tract infection,appeared in the 1980 s.PRCV is considered nonpathogenic since its infection course is mild or subclinical.Since its appearance,pig populations have become immune to both PRCV and TGEV,leading to a significant reduction in the clinical and economic importance of TGEV.TGEV,PEDV and PDCoV are enteropathogenic CoV and cause clinically indistinguishable acute gastroenteritis in all age groups of pigs.PDCoV and SADS-CoV have emerged in 2014(US)and in 2017(China),respectively.Rapid diagnosis is crucial for controlling CoV infections and preventing them from spreading.Since vaccines are available only for some porcine CoV,prevention should focus mainly on a high level of biosecurity.In view of the diversity of CoV and the potential risk factors associated with zoonotic emergence,updating the knowledge concerning this area is essential.
文摘Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a highly contagious virus that can transmit through respiratory droplets,aerosols,or contacts.Frequent touching of contaminated surfaces in public areas is therefore a potential route of SARS-CoV-2 transmission.The inanimate surfaces have often been described as a source of nosocomial infections.However,summaries on the transmissibility of coronaviruses from contaminated surfaces to induce the coronavirus disease 2019 are rare at present.This review aims to summarize data on the persistence of different coronaviruses on inanimate surfaces.The literature was systematically searched on Medline without language restrictions.All reports with experimental evidence on the duration persistence of coronaviruses on any type of surface were included.Most viruses from the respiratory tract,such as coronaviruses,influenza,SARS-CoV,or rhinovirus,can persist on surfaces for a few days.Persistence time on inanimate surfaces varied from minutes to up to one month,depending on the environmental conditions.SARSCoV-2 can be sustained in air in closed unventilated buses for at least 30 min without losing infectivity.The most common coronaviruses may well survive or persist on surfaces for up to one month.Viruses in respiratory or fecal specimens can maintain infectivity for quite a long time at room temperature.Absorbent materials like cotton are safer than unabsorbent materials for protection from virus infection.The risk of transmission via touching contaminated paper is low.Preventive strategies such as washing hands and wearing masks are critical to the control of coronavirus disease 2019.
基金supported by grants from National Science and Technology Major Project of China(2018ZX10712001-018,2017ZX10303405-002,2017ZX10303405005-002)National Science and Technology of China(2017FY101202)+2 种基金National Key R&D Program of China(2019YFC1200500 and 2019YFC1200505)Sanming Project of Medicine in Shenzhen(SZSM201811071)Research Units of Discovery of Unknown Bacteria and Function(2018RU010)。
文摘Outbreaks of severe virus infections with the potential to cause global pandemics are increasingly concerning.One type of those commonly emerging and re-emerging pathogens are coronaviruses(SARS-Co V,MERS-Co V and SARS-Co V-2).Wild animals are hosts of different coronaviruses with the potential risk of cross-species transmission.However,little is known about the reservoir and host of coronaviruses in wild animals in Qinghai Province,where has the greatest biodiversity among the world's high-altitude regions.Here,from the next-generation sequencing data,we obtained a known beta-coronavirus(beta-Co V)genome and a novel delta-coronavirus(delta-Co V)genome from faecal samples of 29 marmots,50 rats and 25 birds in Yushu Tibetan Autonomous Prefecture,Qinghai Province,China in July 2019.According to the phylogenetic analysis,the beta-Co V shared high nucleotide identity with Coronavirus HKU24.Although the novel delta-Co V(Mt Co V)was closely related to Sparrow deltacoronavirus ISU42824,the protein spike of the novel delta-Co V showed highest amino acid identity to Sparrow coronavirus HKU17(73.1%).Interestingly,our results identified a novel host(Montifringilla taczanowskii)for the novel delta-Co V and the potential cross-species transmission.The most recent common ancestor(t MRCA)of Mt Co Vs along with other closest members of the species of Coronavirus HKU15 was estimated to be 289 years ago.Thus,this study increases our understanding of the genetic diversity of beta-Co Vs and deltaCo Vs,and also provides a new perspective of the coronavirus hosts.
文摘Although coronavirus(CoV)infection is often characterized by respiratory symptoms,the virus can also result in extrapulmonary symptoms,especially the symptoms related to the digestive system.The outbreak of coronavirus disease 2019(COVID-19)is currently the world’s most pressing public health threat and has a significant impact on civil societies and the global economy.The occurrence of digestive symptoms in patients with COVID-19 is closely related to the development and prognosis of the disease.Moreover,thus far,there are no specific antiviral drug or vaccine approved for the treatment or prevention of COVID-19.Therefore,we elaborate on the effects of CoVs on the digestive system and the potential underlying mechanisms.
基金funded by the National Natural Science Foundation of China(81290341)Scientific and Technological Basis Special Project(2013FY113500)+1 种基金China Mega-Project for Infectious Disease(2014ZX 10004001-003)from the Minister of Science and Technology of the People’s Republic of ChinaUSNIAID(R01AI110964)
文摘Since the 2002–2003 severe acute respiratory syndrome(SARS) outbreak prompted a search for the natural reservoir of the SARS coronavirus, numerous alpha- and betacoronaviruses have been discovered in bats around the world. Bats are likely the natural reservoir of alpha- and betacoronaviruses, and due to the rich diversity and global distribution of bats, the number of bat coronaviruses will likely increase. We conducted a surveillance of coronaviruses in bats in an abandoned mineshaft in Mojiang County, Yunnan Province, China, from 2012–2013. Six bat species were frequently detected in the cave: Rhinolophus sinicus, Rhinolophus affinis, Hipposideros pomona, Miniopterus schreibersii, Miniopterus fuliginosus, and Miniopterus fuscus. By sequencing PCR products of the coronavirus RNA-dependent RNA polymerase gene(Rd Rp), we found a high frequency of infection by a diverse group of coronaviruses in different bat species in the mineshaft. Sequenced partial Rd Rp fragments had 80%–99% nucleic acid sequence identity with well-characterized Alphacoronavirus species, including Bt CoV HKU2, Bt CoV HKU8, and Bt CoV1,and unassigned species Bt CoV HKU7 and Bt CoV HKU10. Additionally, the surveillance identified two unclassified betacoronaviruses, one new strain of SARS-like coronavirus, and one potentially new betacoronavirus species. Furthermore, coronavirus co-infection was detected in all six bat species, a phenomenon that fosters recombination and promotes the emergence of novel virus strains. Our findings highlight the importance of bats as natural reservoirs of coronaviruses and the potentially zoonotic source of viral pathogens.
基金This work was funded by the Guangdong Major Project of Basic and Applied Basic Research(No.2020B0301030007)the Natural Science Foundation of Guangdong Province(2022A1515012473,2020A1515010220)the Science and Technology Program of Guangzhou City of China(2023B03J1310.)。
文摘The outbreak of the COVID-19 epidemic in 2020 has caused unprecedented panic among all mankind,pointing the major importance of effective treatment.Since the emergence of the swine acute diarrhea syndrome coronavirus(SADS-CoV)at the end of 2017,multiple reports have indicated that the bat-related SADS-CoV possesses a potential threat for cross-species transmission.Vaccines and antiviral drugs development deserve more attention.In this study,we found that the HER2 phosphorylation inhibitor(CP-724714)inhibited SADS-CoV infection in a dose-dependent manner.Further validation demonstrated that CP-724714 affected at the post-entry stage of SADS-CoV infection cycle.Also,efficient SADS-CoV infection required the activation of HER2 and its cascade Ras-Raf-Mek-Erk signaling pathway.In addition,CP-724714 has a broad-spectrum anti-swine diarrhea coronaviruses activity,and can dose-dependently combat SADS-CoV,porcine epidemic diarrhea virus(PEDV),porcine deltacoronavirus(PDCoV)and transmissible gastroenteritis virus(TGEV)infection in vitro with a specificity index of greater than 21.98,9.38,95.23 and 31.62,respectively.These results highlight the potential utility of CP-724714 or antiviral drugs targeting with HER2 and its cascade Ras-Raf-Mek-Erk signaling pathway as host-targeted SADS-CoV and other related coronaviruses therapeutics.
文摘New coronavirus referred to SARS-CoV-2 has caused a worldwide pandemic(COVID-19)declared by WHO.Coronavirus disease 2019(COVID-19)is an infectious disease with severe acute respiratory syndrome caused by coronavirus-2(SARS-CoV-2).SARS-CoV-2 is akin to SARS-CoV,which was the causative agent of severe acute respiratory syndrome(SARS)in 2002 as well as to that of Middle East respiratory syndrome(MERS)in 2012.SARS-CoV-2 has been revealed to belong to Coronaviridiae family as a member ofβ-coronaviruses.It has a positive-sense single-stranded RNA with the largest RNA genome.Since its genomic sequence has a notable similarity to that of SARS-CoV,antiviral drugs used to treat SARS and MERS are now being also applied for COVID-19 treatment.In order to combat SARS-CoV-2,many drug and vaccine development studies at experimental and clinical levels are currently conducted worldwide.In this sense,medicinal plants and the pure natural molecules isolated from plants have been reported to exhibit significant inhibitory antiviral activity against SARS-CoV and other types of coronaviruses.In the present review,plant extracts and natural molecules with the mentioned activity are discussed in order to give inspiration to researchers to take these molecules into consideration against SARS-CoV-2.
基金funded by the National Natural Science Foundation of China (81290341)China Mega-Project for Infectious Disease (2014ZX10004001-003) from the Minister of Science and Technology of the People’s Republic of ChinaUSNIAID (R01AI110964)
文摘Dear Editor,The 2002–2003 severe acute respiratory syndrome coronavirus（SARS-CoV）（Drosten et al.,2003）caused human pandemics that began in China and spread globally.Subsequently,
文摘In this paper, we report a multiple sequence alignment result on the basis of 10 amino acid sequences of the M protein, which come from different coronaviruses (4 SARS associated and 6 others known). The alignment model was based on the profile HMM (Hidden Markov Model), and the model training was implemented through the SAHMM (Self Adapting Hidden Markov Model) software developed by the authors.
基金supported by the National Natural Science Foundation of China (Grant No.31372440)
文摘The surface glycoproteins of coronaviruses play an important role in receptor binding and cell entry. Different coronaviruses interact with their specific receptors to enter host cells. Lentiviruses pseudotyped with their spike proteins(S) were compared to analyze the entry efficiency of various coronaviruses. Our results indicated that S proteins from different coronaviruses displayed varied abilities to mediate pseudotyped virus infection. Furthermore, the cell tropisms of porcine epidemic diarrhea virus(PEDV) and transmissible gastroenteritis virus(TGEV) have been characterized by live and pseudotyped viruses. Both live and pseudoviruses could infected VeroCCL-81(monkey kidney), Huh-7(human liver), and PK-15(pig kidney) cells efficiently. CCL94(cat kidney) cells could be infected efficiently by TGEV but not PEDV. Overall, our study provides new insights into the mechanisms of viral entry and forms a basis for antiviral drug screening.
基金funded by the National Natural Science Foundation of China(No.32041001,81902070,U2002218)the Provincial Natural Science Foundation of Hunan Province(No.2019JJ20004 and 2019JJ50035).
文摘The frequent emergence of coronavirus(CoV)epidemics has seriously threatened public health and stock farming.The major hosts for CoVs are birds and mammals.Although most CoVs inhabit their specific natural hosts,some may occasionally cross the host barrier to infect livestock and even people,causing a variety of diseases.Since the beginning of the new century,increasing attention has been given to research on CoVs due to the emergence of highly pathogenic and genetically diverse CoVs that have caused several epidemics,including the recent COVID-19 pandemic.CoVs belong to the Coronaviridae family of the Nidovirales order.Recently,advanced techniques for viral detection and viral genome analyses have enabled characterization of many new nidoviruses than ever and have greatly expanded the Nidovirales order with new classification and nomenclature.Here,we first provide an overview of the latest research progress in the classification of the Nidovirales order and then introduce the host range,genetic variation,genomic pattern and pathogenic features of epidemic CoVs and other epidemic viruses.This information will promote understanding of the phylogenetic relationship and infectious transmission of various pathogenic nidoviruses,including epidemic CoVs,which will benefit virological research and viral disease control.
基金supported by the National Key R&D Program of China(2021YFC2300901 to P.Z.)China Natural Science Foundation for outstanding scholars(82325032 to P.Z.)+1 种基金the Self-Supporting Program of Guangzhou Laboratory(SRPG22-001 to P.Z.GZNL2023A01001 to ZLS).
文摘Bats are the natural reservoir hosts for SARS-related coronavirus(SARSr-CoV)and other highly pathogenic microorganisms.Therefore,it is conceivable that an individual bat may harbor multiple microbes.However,there is limited knowledge on the overall co-circulation of microorganisms in bats.Here,we conducted a 16-year monitoring of bat viruses in south and central China and identified 238 SARSr-CoV positive samples across nine bat species from ten provinces or administrative districts.Among these,76 individual samples were selected for further metagenomics analysis.We found a complex microenvironment characterized by the general cocirculation of microbes from two different sources:mammal-associated viruses or environment-associated microbes.The later includes commensal bacteria,enterobacteria-related phages,and insect or fungal viruses of food origin.Results showed that 25%(19/76)of the samples contained at least one another mammal-associated virus,notably alphacoronaviruses(13/76)such as AlphaCoV/YN2012,HKU2-related CoV and AlphaCoV/Rf-HuB2013,along with viruses from other families.Notably,we observed three viruses co-circulating within a single bat,comprising two coronavirus species and one picornavirus.Our analysis also revealed the potential presence of pathogenic bacteria or fungi in bats.Furthermore,we obtained 25 viral genomes from the 76 bat SARSr-CoV positive samples,some of which formed new evolutionary lineages.Collectively,our study reveals the complex microenvironment of bat microbiome,facilitating deeper investigations into their pathogenic potential and the likelihood of cross-species transmission.
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supported by the National Institute of Allergy and Infectious Diseases (NIAID contract HHSN266200700005C)European Research Project SARS-DTV (contract no: SP22-CT-2004)
文摘Zoonotic transmissions of emerging pathogens from wildlife to human have shaped the history of mankind. These events have also highlighted our poor understanding of microorganisms circulated in wild animals. Coronaviruses and astroviruses,which can be found from a wide range of mammals,were recently detected in bats. Strikingly,these bat viruses are genetically highly diverse and these interesting findings might help to better understand the evolution and ecology of these viruses. The discoveries of these novel bats viruses not only suggested that bats are important hosts for these virus families,but also reiterated the role of bats as a reservoir of viruses that might pose a zoonotic threat to human health.
文摘BACKGROUND Ribavirin is a broad-spectrum nucleoside antiviral drug with multimodal mechanisms of action,which supports its longevity and quality as a clinical resource.It has been widely administered for measles and coronavirus infections.Despite the large amount of data concerning the use of ribavirin alone or in combination for measles,severe acute respiratory syndrome,Middle East respiratory syndrome,and coronavirus disease 2019(COVID-19)outbreaks,the conclusions of these studies have been contradictory.Underlying reasons for these discrepancies include possible study design inaccuracies and failures and misinterpretations of data,and these potential confounds should be addressed.AIM To determine the confounding factors of ribavirin treatment studies and propose a therapeutic scheme for COVID-19.METHODS PubMed database was searched over a period of five decades utilizing the terms“ribavirin”alone or combined with other compounds in measles,severe acute respiratory syndrome,Middle East respiratory syndrome,and COVID-19 infections.The literature search was performed and described according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Articles were considered eligible when they reported on ribavirin dose regimens and/or specified outcomes concerning its efficacy and/or possible adverseeffects.In vitro and animal studies were also retrieved.A chapter on ribavirin’s pharmacology was included as well.RESULTS In addition to the difficulties and pressures of an emerging pandemic,there is the burden of designing and conducting well-organized,double-blind,randomized controlled trials.Many studies have succumbed to specific pitfalls,one of which was identified in naturally ribavirin-resistant Vero cell lines in in vitro studies.Other pitfalls include study design inconsistent with the well-established clinical course of disease;inappropriate pharmacology of applied treatments;and the misinterpretation of study results with misconceived generalizations.A comprehensive treatment for COVID-19 is proposed,documented by thorough,longterm investigation of ribavirin regimens in coronavirus infections.CONCLUSION A comprehensive treatment strictly tailored to distinct disease stages was proposed based upon studies on ribavirin and coronavirus infections.
