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简介：摘要我国武汉出现的新型冠状病毒肺炎疫情经过迅速发展已对全国造成严重影响，但到目前为止对新型冠状病毒肺炎病理变化和发病机制却知之甚少。该文总结重症流感病毒H1N1、高致病性禽流感病毒H5N1、SARS-CoV、MERS-CoV及2019-nCoV几种引起重大疫情病毒感染性疾病的病理改变，尸检肺组织均表现为弥漫性肺泡损伤（diffuse alveolar damage，DAD），但不同病毒引起的病理表现存在差异，重症流感病毒2009 H1N1病毒与受体α-2，6-SA及α-2，3-SA结合，除DAD病变外，常伴有上呼吸道、气管、支气管和细支气管的炎性病变，且较易合并细菌感染。高致病性禽流感病毒H5N1主要结合α-2，3-SA受体，主要累及肺泡上皮及细支气管，少见上呼吸道及气管、支气管病变，常伴局灶肺出血及肺组织坏死，机化及纤维化较少见。SARS-CoV通过结合血管紧张素转换酶2（ACE2）进入细胞，病变与病程相关，DAD渗出期一般见于病程10~14 d死亡患者。病程大于10 d患者表现为DAD机化期，并常伴有闭塞性细支气管炎伴机化性肺炎样改变及肺泡腔内显著多核巨细胞。SARS-CoV及H5N1感染患者肺外器官均可见脾和淋巴结内淋巴细胞耗竭、急性肾小管坏死、骨髓内噬血细胞现象。

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简介：AnnotationofthegenomesequenceoftheSARS-CoV(severeacuterespiratorysyndrome-associatedcoronavirus)isindispensabletounderstanditsevolutionandpathogenesis.WehaveperformedafullannotationoftheSARS-CoVgenomesequencesbyusingannotationprogramspubliclyavailableordevelopedbyourselves.Totally,21openreadingframes(ORFs)ofgenesorputativeuncharacterizedproteins(PUPs)werepredicted.SevenPUPshadnotbeenreportedpreviously,andtwoofthemwerepredictedtocontaintransmembraneregions.EightORFspartiallyoverlappedwithorembeddedintothoseofknowngenes,revealingthattheSARS-CoVgenomeisasmallandcompactonewithoverlappedcodingregions.ThemoststrikingdiscoveryisthatanORFlocatesontheminusstrand.Wehavealsoannotatednon-codingregionsandidentifiedthetranscriptionregulatingsequences(TRS)intheintergenicregions.TheanalysisofTRSsupportstheminusstrandextendingtranscriptionmechanismofcoronavirus.TheSNPanalysisofdifferentisolatesrevealsthatmutationsofthesequencesdonotaffectthepredictionresultsofORFs.

简介：Knowledgeoftheevolutionofpathogensisofgreatmedicalandbiologicalsignificancetotheprevention,diagnosis,andtherapyofinfectiousdiseases.InordertounderstandtheoriginandevolutionoftheSARS-CoV(severeacuterespiratorysyndrome-associatedcoronavirus),wecollectedcompletegenomesequencesofallvirusesavailableinGenBank,andmadecomparativeanalyseswiththeSARSCoV.GenomicsignatureanalysisdemonstratesthatthecoronavirusesalltaketheTGTTastheirrichesttetranucleotideexcepttheSARS-CoV.Adetailedanalysisoftheforty-twocompleteSARS-CoVgenomesequencesrevealedtheexistenceoftwodistinctgenotypes,andshowedthattheseisolatescouldbeclassifiedintofourgroups.OurmanualanalysisoftheBLASTNresultsdemonstratesthattheHE(hemagglutinin-esterase)geneexistsintheSARS-CoV,andmanymutationsmadeitunfamiliartous.

简介：Adatasetof103SARS-CoVisolates(101humanpatientsand2palmcivets)wasinvestigatedondifferentaspectsofgenomepolymorphismandisolateclassification.Thenumberandthedistributionofsinglenucleotidevariations(SNVs)andinsertionsanddeletions,withrespecttoa"profile",weredeterminedanddiscussed("profile"beingasequencecontainingthemostrepresentedletterperposition).Distributionofsubstitutioncategoriespercodonpositions,aswellassynonymousandnon-synonymoussubstitutionsincodingregionsofannotatedisolates,wasdetermined,alongwithaminoacid(a.a.)propertychanges.Similaranalysiswasperformedforthespike(S)proteininalltheisolates(55ofthembeingpredictedforthefirsttime).TheratioKa/KsconfirmedthattheSgenewassubjectedtotheDarwinianselectionduringvirustransmissionfromanimalstohumans.Isolatesfromthedatasetwereclassifiedaccordingtogenomepolymorphismandgenotypes.Genomepolymorphismyieldstotwogroups,onewithasmallnumberofSNVsandanotherwithalargenumberofSNVs,withuptofoursubgroupswithrespecttoinsertionsanddeletions.Weidentifiedthreebasicnine-locusgenotypes:TTTT/TTCGG,CGCC/TTCAT,andTGCC/TTCGT,withfoursubgenotypes.Bothclassificationsproposedareinaccordancewiththenewinsightsintopossibleepidemiologicalspread,bothinspaceandtime.

简介：Thenucleocapsidprotein(Nprotein)hasbeenfoundtobeanantigenicproteininanumberofcoronaviruses.WhethertheNproteininsevereacuterespiratorysyndrome-associatedcoronavirus(SARS-CoV)isantigenicremainstobeelucidated.UsingWesternblotandEnzyme-linkedImmunosorbentAssay(ELISA),therecombinantNproteinsandthesynthesizedpeptidesderivedfromtheNproteinwerescreenedinserafromSARSpatients.AllpatientserainthisstudydisplayedstrongpositiveimmunoreactivitiesagainsttherecombinantNproteins,whereasnormalseragavenegativeimmunoresponsestotheseproteins,indicatingthattheNproteinofSARS-CoVisanantigenicprotein.Furthermore,theepitopesitesintheNproteinweredeterminedbycompetitionexperiments,inwhichtherecombinantproteinsorthesynthesizedpeptidescompetedagainsttheSARS-CoVproteinstobindtotheantibodiesraisedinSARSsera.OneepitopesitelocatedattheC-terminuswasconfirmedasthemostantigenicregioninthisprotein.AdetailedscreeningofpeptidewithELISAdemonstratedthattheaminosequencefromCodons371to407wastheepitopesiteattheC-terminusoftheNprotein.UnderstandingoftheepitopesitescouldbeverysignificantfordevelopinganeffectivediagnosticapproachtoSARS.

简介：摘要近年来，国际上出现了一种新型的无功补偿装置MERS。该装置结构简单，运用一些基本的控制方法即可实现连续可调的无功功率补偿，已在串联补偿应用中得到证明。MERS串联在电源和负载之间，通过控制其等效电容和负载感抗在基波频率上的串联谐振，来提高电源的功率因数。本文提出一种新型的静止无功补偿器。首先提出了HALF-MERS并联补偿时的控制方法，建立了并联补偿时HALF-MERS的数学模型，进一步基于该数学模型对并联型HALF-MERS进行了性能分析，并进行了实验验证。

简介：AbstractIn December of 2019, several cases of atypical pneumonia caused by an unknown agent were reported in Wuhan, the capital city of Hubei Province in China. In early January 2020, it was announced that these cases were caused by a novel coronavirus. The virus was later named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which causes a disease associated with atypical pneumonia termed Corona virus disease 2019 (COVID-19). Several respiratory viruses, including coronaviruses and influenza viruses tend to have prominent peaks of infection during colder seasons, especially in temperate regions. The cold temperatures, along with accompanying dry conditions can drive respiratory tract infections by assisting with viral transmission, weakening the human immune system, and increasing viral molecular stability. Though the topic of SARS-CoV-2 transmission and warm weather has been associated with misinformation campaigns, it is worth investigating since an informative answer may give an indication of the future behavior of SARS-CoV-2.

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简介：TotesttheantigenicactivityofMprotein(Mcprotein)intheinnermembraneofSARS-CoV,SARS-CoVMcprotein'sbaseslocatinginsidethemembranewerecloned,theHis-fusionproteinwasexpressedinE.coliandanalyzedforitsantigenicactivity.Amongthose7clinicallydiagnosedpatients'sera,therewere5positiveand2negativeinreactionwithHis-fusionprotein.Allofthe20healthypersons'seraandrabbitanti-OC43and229EwereofnegativereactionwithHis-fusionprotein.TheanimalsimmunizedwithHis-fusionproteinhaveproducedmulti-clonalantibody.TheHis-fusionproteincouldspeciallyreactwithclinicallydiagnosedSARSpatients'seraandtheanimalsimmunizedwithHis-fusionproteincouldproducespecificallymulti-clonalantibody,butitcouldnotreactwiththeseraofhealthypersonsandtherabbitanti-OC43and229E.

简介：TheE(envelope)proteinisthesmalleststructuralproteininallcoronavirusesandistheonlyviralstructuralproteininwhichnovariationhasbeendetected.WeconductedgenomesequencingandphylogeneticanalysesofSARS-CoV.Basedongenomesequencing,wepredictedtheEproteinisatransmembrane(TM)pro-teincharacterizedbyaTMregionwithstronghydrophobicityandα-helixcon-formation.Weidentifiedasegment(NH2-_L-Cys-A-Y-Cys-Cys-N_-COOH)inthecarboxyl-terminalregionoftheEproteinthatappearstoformthreedisulfidebondswithanothersegmentofcorrespondingcysteinesinthecarboxyl-terminusoftheS(spike)protein.ThesebondspointtoapossiblestructuralassociationbetweentheEandSproteins.OurphylogeneticanalysesoftheEproteinsequencesinallpub-lishedcoronavirusesplaceSARS-CoVinanindependentgroupinCoronaviridaeandsuggestanon-humananimalorigin.

简介：Thecorona-likespikesorpeplomersonthesurfaceofthevirionunderelectronicmicroscopearethemoststrikingfeaturesofcoronaviruses.TheS(spike)proteinisthelargeststructuralprotein,with1,255aminoacids,intheviralgenome.Itsstructurecanbedividedintothreeregions:alongN-terminalregionintheexte-rior,acharacteristictransmembrane(TM)region,andashortC-terminusintheinteriorofavirion.WedetectedfifteensubstitutionsofnucleotidesbycomparisonswiththeseventeenpublishedSARS-CoVgenomesequences,eight(53.3%)ofwhicharenon-synonymousmutationsleadingtoaminoacidalternationswithpredictedphysiochemicalchanges.ThepossibleantigenicdeterminantsoftheSproteinarepredicted,andtheresultisconfirmedbyELISA(enzyme-linkedimmunosorbentassay)withsynthesizedpeptides.AnotherprofoundfindingisthatthreedisulfidebondsaredefinedattheC-terminuswiththeN-terminusoftheE(envelope)pro-tein,basedonthetypicalsequenceandpositions,thusestablishingthestructuralconnectionwiththesetwoimportantstructuralproteins,ifconfirmed.Phyloge-neticanalysisrevealsseveralconservedregionsthatmightbepotentdrugtargets.

简介：AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses spread unscrupulously virtually every corner on the planet in a very quick speed leading to an unprecedented world pandemic of COVID-19 claiming a great many of people’s life. Paramount importance has been given to the studies on the virus itself including genomic variation and viron structure, as well as cell entry pathway and tissue residence. Other than that, to learn the main characteristic of host immunity responding to SARS-CoV-2 infection is an eminent task for restraining virus and controlling disease progress. Beside antibody production in response to SARS-CoV-2 infection, host cellular immunity plays an indispensable role in impeding virus replication and expansion at various stages of COVID-19 disease. In this review, we summarized the recent knowledge regarding the aberrant regulation and dysfunction of multiple immune cells during SARS-CoV-2 infection. This includes the dysregulation of immune cell number, Th polarity, cytokine storm they implicated with, as well as cell function exhaustion after chronic virus stimulation. Notwithstanding that many obstacles remain to be overcome, studies on immunotherapy for COVID-19 treatment based on the known features of host immunity in response to SARS-CoV-2 infection offer us tangible benefits and hope for making this SARS-CoV-2 pandemic under control.

简介：AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, generating new variants that pose a threat to global health; therefore, it is imperative to obtain safe and broad-spectrum antivirals against SARS-CoV-2 and its variants. To this end, we screened compounds for their ability to inhibit viral entry, which is a critical step in virus infection. Twenty compounds that have been previously reported to inhibit SARS-CoV-2 replication were tested by using pseudoviruses containing the spike protein from the original strain (SARS-CoV-2-WH01). The cytotoxicity of these compounds was determined. Furthermore, we identified six compounds with strong antagonistic activity against the WH01 pseudovirus, and low cytotoxicity was identified. These compounds were then evaluated for their efficacy against pseudoviruses expressing the spike protein from B.1.617.2 (Delta) and B.1.1.529 (Omicron), the two most prevalent circulating strains. These assays demonstrated that two phenothiazine compounds, trifluoperazine 2HCl and thioridazine HCl, inhibit the infection of Delta and Omicron pseudoviruses. Finally, we discovered that these two compounds were highly effective against authentic SARS-CoV-2 viruses, including the WH01, Delta, and Omicron strains. Our study identified potential broad-spectrum SARS-CoV-2 inhibitors and provided insights into the development of novel therapeutics.

简介：AbstractOmicron (B.1.1.529), the fifth variant of concern (VOC) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was firstly identified in November 2021 in South Africa. Omicron contains far more genome mutations than any other VOCs ever found, raising significant concerns about its increased transmissibility and immune evasion. Here, we report the importation of the Omicron variant into Beijing, China, in December 2021. Full-length genome sequences of five imported strains were obtained, with their genetic features characterized. Each strain contained 57 to 61 nucleotide substitutions, 39 deletions, and 9 insertions in the genome. Thirty to thirty-two amino acid changes were found in the spike proteins of the five strains. The phylogenetic tree constructed by the maximum likelihood method showed that all five imported genomes belonged to Omicron (BA.1) (alias of B.1.1.529.1), which is leading to the current surge of coronavirus disease 2019 (COVID-19) cases worldwide. The globally increased COVID-19 cases driven by the Omicron variant pose a significant challenge to disease prevention and control in China. Continuous viral genetic surveillance and increased testing among international travellers are required to contain this highly contagious variant.