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:SincetheoutbreakofaSARSepidemiclastyear,significantadvanceshavebeenmadeonourunderstandingofthemechanismsofinteractionbetweentheSARScoronavirus(CoV)andtheimmunesystem.StronghumoralresponseshavebeenfoundinmostpatientsfollowingSARS-CoVinfection,withhightitersofneutralizingAbspresentintheirconvalescentsera.Thenucleocapsid(N)andspike(S)proteinsofSARS-CoVappeartobethedominantantigensrecognizedbyserumAbs.CD4+TcellresponsesagainsttheNproteinhavebeenobservedinSARSpatientsandanHLA-A2-restrictedcytotoxicTlymphocyteepitopeintheSproteinhasbeenidentified.ItislikelythattheimmuneresponsesinducedbySARS-CoVinfectioncouldalsocausepathologicaldamagetothehost,especiallyinthecaseofproinflammatorycytokines.ThereisalsoevidencesuggestingthatSARS-CoVmightbeabletodirectlyinvadecellsoftheimmunesystem.OurunderstandingontheinteractionbetweenSARS-CoV,theimmunesystemandlocaltissuesisessentialtofuturediagnosis,controlandtreatmentofthisverycontagiousdisease.
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.
简介:AbstractAt present, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread worldwide, which has emerged multiple variants and brought a threat to global public health. To analyze the genomic characteristics and variations of SARS-CoV-2 imported into Beijing, we collected the respiratory tract specimens of 112 cases of coronavirus disease 2019 (COVID-19) from January to September 2021 in Beijing, China, including 40 local cases and 72 imported cases. The whole-genome sequences of the viruses were sequenced by the next-generation sequencing method. Variant markers and phylogenic features of SARS-CoV-2 were analyzed. Our results showed that in all 112 sequences, the mutations were concentrated in spike protein. D614G was found in all sequences, and mutations including L452R, T478K, P681R/H, and D950N in some cases. Furthermore, 112 sequences belonged to 23 lineages by phylogenetic analysis. B.1.1.7 (Alpha) and B.1.617.2 (Delta) lineages were dominant. Our study drew a variation image of SARS-CoV-2 and could help evaluate the potential risk of COVID-19 for pandemic preparedness and response.