COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses Muhammad Adnan Shereen
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JournalofAdvancedResearch24(2020)91–98
Contentslistsavailableat ScienceDirect
journalhomepag e:www.elsevier.c om/locate/jare
COVID-19infection:Origin,transmission,andcharacteristicsofhuman coronaviruses
MuhammadAdnanShereen a,b,1,SulimanKhan a,1,⇑,AbeerKazmi c,NadiaBashir a,RabeeaSiddique a
a TheDepartmentofCerebrovascularDiseases,TheSecondAffiliatedHospitalofZhengzhouUniversity,Zhengzhou,PRChina
b StateKeyLaboratoryofVirology,CollegeofLifeSciences,WuhanUniversity,Wuhan,PRChina
c CollegeofLifeSciences,WuhanUniversity,Wuhan,PRChina
graphicalabstract
articleinfo
Articlehistory:
Received15March2020
Accepted15March2020
Availableonline16March2020
Keywords: Coronaviruses
COVID-19
Origin Outbreak Spread
PeerreviewunderresponsibilityofCairoUniversity.
⇑ Correspondingauthor.
abstract
Thecoronavirusdisease19(COVID-19)isahighlytransmittableandpathogenicviralinfectioncausedby severeacuterespiratorysyndromecoronavirus2(SARS-CoV-2),whichemergedinWuhan,Chinaand spreadaroundtheworld.GenomicanalysisrevealedthatSARS-CoV-2isphylogeneticallyrelatedtosevereacuterespiratorysyndrome-like(SARS-like)batviruses,thereforebatscouldbethepossibleprimary reservoir.Theintermediatesourceoforiginandtransfertohumansisnotknown,however,therapid humantohumantransferhasbeenconfirmedwidely.Thereisnoclinicallyapprovedantiviraldrugor vaccineavailabletobeusedagainstCOVID-19.However,fewbroad-spectrumantiviraldrugshavebeen evaluatedagainstCOVID-19inclinicaltrials,resultedinclinicalrecovery.Inthecurrentreview,wesummarizeandcomparativelyanalyzetheemergenceandpathogenicityofCOVID-19infectionandprevious humancoronavirusessevereacuterespiratorysyndromecoronavirus(SARS-CoV)andmiddleeastrespiratorysyndromecoronavirus(MERS-CoV).Wealsodiscusstheapproachesfordevelopingeffectivevaccinesandtherapeuticcombinationstocopewiththisviraloutbreak.
2020THEAUTHORS.PublishedbyElsevierBVonbehalfofCairoUniversity.Thisisanopenaccessarticle undertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).
E-mailaddress: suliman.khan18@mails.ucas.ac.cn (S.Khan).
1 Contributedequally(M.A.SandS.K).
Introduction
CoronavirusesbelongtotheCoronaviridaefamilyintheNidoviralesorder.Coronarepresentscrown-likespikesontheoutersurfaceofthevirus;thus,itwasnamedasacoronavirus.
https://doi.org/10.1016/j.jare.2020.03.005 2090-1232/ 2020THEAUTHORS.PublishedbyElsevierBVonbehalfofCairoUniversity. ThisisanopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Coronavirusesareminuteinsize(65–125nmindiameter)and containasingle-strandedRNAasanucleicmaterial,sizeranging from26to32kbsinlength(Fig.1).Thesubgroupsofcoronaviruses familyarealpha(a),beta(b),gamma(c)anddelta(d)coronavirus. Thesevereacuterespiratorysyndromecoronavirus(SARS-CoV), H5N1influenzaA,H1N12009andMiddleEastrespiratorysyndromecoronavirus(MERS-CoV)causeacutelunginjury(ALI)and acuterespiratorydistresssyndrome(ARDS)whichleadstopulmonaryfailureandresultinfatality.Theseviruseswerethought toinfectonlyanimalsuntiltheworldwitnessedasevereacuterespiratorysyndrome(SARS)outbreakcausedbySARS-CoV,2002in Guangdong,China [1].Onlyadecadelater,anotherpathogenic coronavirus,knownasMiddleEastrespiratorysyndromecoronavirus(MERS-CoV)causedanendemicinMiddleEasterncountries [2]
Recentlyattheendof2019,Wuhananemergingbusinesshub ofChinaexperiencedanoutbreakofanovelcoronavirusthatkilled morethaneighteenhundredandinfectedoverseventythousand individualswithinthefirstfiftydaysoftheepidemic.Thisvirus wasreportedtobeamemberofthe b groupofcoronaviruses. ThenovelviruswasnamedasWuhancoronavirusor2019novel coronavirus(2019-nCov)bytheChineseresearchers.TheInternationalCommitteeonTaxonomyofViruses(ICTV)namedthevirus asSARS-CoV-2andthediseaseasCOVID-19 [3–5].Inthehistory, SRAS-CoV(2003)infected8098individualswithmortalityrateof 9%,across26contriesintheworld,ontheotherhand,novelcorona virus(2019)infected120,000induvidualswithmortalityrateof 2.9%,across109countries,tilldateofthiswriting.Itshowsthat thetransmissionrateofSARS-CoV-2ishigherthanSRAS-CoVand thereasoncouldbegeneticrecombinationeventatSproteininthe RBDregionofSARS-CoV-2mayhaveenhanceditstransmission ability.Inthisreviewarticle,wediscusstheoriginationofhuman coronavirusesbriefly.WefurtherdiscusstheassociatedinfectiousnessandbiologicalfeaturesofSARSandMERSwithaspecialfocus onCOVID-19.
Comparativeanalysisofemergenceandspreadingof coronaviruses
In2003,theChinesepopulationwasinfectedwithaviruscausingSevereAcuteRespiratorySyndrome(SARS)inGuangdongprovince.TheviruswasconfirmedasamemberoftheBetacoronavirussubgroupandwasnamedSARS-CoV [6,7].Theinfected patientsexhibitedpneumoniasymptomswithadiffusedalveolar injurywhichleadtoacuterespiratorydistresssyndrome(ARDS).
SARSinitiallyemergedinGuangdong,Chinaandthenspread rapidlyaroundtheglobewithmorethan8000infectedpersons and776deceases.Adecadelaterin2012,acoupleofSaudiArabian
nationalswerediagnosedtobeinfectedwithanothercoronavirus. Thedetectedviruswasconfirmedasamemberofcoronaviruses andnamedastheMiddleEastRespiratorySyndromeCoronavirus (MERS-CoV).TheWorldhealthorganizationreportedthatMERScoronavirusinfectedmorethan2428individualsand838deaths [8].MERS-CoVisamemberbeta-coronavirussubgroupandphylogeneticallydiversefromotherhuman-CoV.TheinfectionofMERSCoVinitiatesfromamildupperrespiratoryinjurywhileprogressionleadstosevererespiratorydisease.SimilartoSARScoronavirus,patientsinfectedwithMERS-coronavirussufferpneumonia,followedbyARDSandrenalfailure [9].
Recently,bytheendof2019,WHOwasinformedbytheChinesegovernmentaboutseveralcasesofpneumoniawithunfamiliaretiology.TheoutbreakwasinitiatedfromtheHunanseafood marketinWuhancityofChinaandrapidlyinfectedmorethan 50peoples.TheliveanimalsarefrequentlysoldattheHunanseafoodmarketsuchasbats,frogs,snakes,birds,marmotsandrabbits [10].On12January2020,theNationalHealthCommissionofChina releasedfurtherdetailsabouttheepidemic,suggestedviralpneumonia [10].Fromthesequence-basedanalysisofisolatesfromthe patients,theviruswasidentifiedasanovelcoronavirus.Moreover, thegeneticsequencewasalsoprovidedforthediagnosisofviral infection.Initially,itwassuggestedthatthepatientsinfectedwith WuhancoronavirusinducedpneumoniainChinamayhavevisited theseafoodmarketwhereliveanimalsweresoldormayhaveused infectedanimalsorbirdsasasourceoffood.However,further investigationsrevealedthatsomeindividualscontractedtheinfectionevenwithnorecordofvisitingtheseafoodmarket.These observationsindicatedahumantothehumanspreadingcapability ofthisvirus,whichwassubsequentlyreportedinmorethan100 countriesintheworld.Thehumantothehumanspreadingof thevirusoccursduetoclosecontactwithaninfectedperson, exposedtocoughing,sneezing,respiratorydropletsoraerosols. Theseaerosolscanpenetratethehumanbody(lungs)viainhalationthroughthenoseormouth(Fig.2) [11–14].
Primaryreservoirsandhostsofcoronaviruses
Thesourceoforiginationandtransmissionareimportanttobe determinedinordertodeveloppreventivestrategiestocontainthe infection.InthecaseofSARS-CoV,theresearchersinitiallyfocused onraccoondogsandpalmcivetsasakeyreservoirofinfection. However,onlythesamplesisolatedfromthecivetsatthefood marketshowedpositiveresultsforviralRNAdetection,suggesting thatthecivetpalmmightbesecondaryhosts [15].In2001the sampleswereisolatedfromthehealthypersonsofHongkongand themolecularassessmentshowed2.5%frequencyrateofantibodiesagainstSARS-coronavirus.Theseindicationssuggestedthat SARS-coronavirusmaybecirculatinginhumansbeforecausingthe outbreakin2003 [16].Lateron,Rhinolophusbatswerealsofound tohaveanti-SARS-CoVantibodiessuggestingthebatsasasourceof viralreplication [17].TheMiddleEastrespiratorysyndrome (MERS)coronavirusfirstemergedin2012inSaudiArabia [9] MERS-coronavirusalsopertainstobeta-coronavirusandhaving camelsasazoonoticsourceorprimaryhost [18].Inarecentstudy, MERS-coronaviruswasalsodetectedinPipistrellusandPerimyotis bats [19],profferingthatbatsarethekeyhostandtransmitting mediumofthevirus [20,21].Initially,agroupofresearcherssuggestedsnakesbethepossiblehost,however,aftergenomicsimilarityfindingsofnovelcoronaviruswithSARS-likebatviruses supportedthestatementthatnotsnakesbutonlybatscouldbe thekeyreservoirs(Table1) [22,23].FurtheranalysisofhomologousrecombinationrevealedthatreceptorbindingspikeglycoproteinofnovelcoronavirusisdevelopedfromaSARS-CoV(CoVZXC21 orCoVZC45)andayetunknownBeta-CoV [24].Nonetheless,to
Fig.2. Thekeyreservoirsandmodeoftransmissionofcoronaviruses(suspectedreservoirsofSARS-CoV-2areredencircled);only a and b coronaviruseshavetheabilityto infecthumans,theconsumptionofinfectedanimalasasourceoffoodisthemajorcauseofanimaltohumantransmissionofthevirusandduetoclosecontactwithan infectedperson,thevirusisfurthertransmittedtohealthypersons.Dottedblackarrowshowsthepossibilityofviraltransferfrombatwhereasthe solidblackarrow representtheconfirmedtransfer.(Forinterpretationofthereferencestocolourinthisfigurelegend,thereaderisreferredtothewebversionofthisarticle.)
Table1
ComparativeanalysisofbiologicalfeaturesofSARS-CoVandSARS-CoV-2.
FeaturesSARS-CoVSARS-CoV-2Reference
EmergencedateNovember2002December2019 [37,79–81] AreaofemergenceGuangdong,ChinaWuhan,China DateoffullycontrolledJuly2003Notcontrolledyet KeyhostsBat,palmcivetsandRaccondogsBat [22,82,83] Numberofcountriesinfected26109 [84]
EntryreceptorinhumansACE2receptorACE2receptor [22,55,85] Signandsymptomsfever,malaise,myalgia,headache,diarrhoea,shivering, coughandshortnessofbreath
Cough,feverandshortnessofbreath [12,23,85]
DiseasecausedSARS,ARDSSARS,COVID-19 [85,86]
Totalinfectedpatients8098123882 [84]
Totalrecoveredpatients732267051 Totaldiedpatients776(9.6%mortalityrate)4473(3.61%mortalityrate)
eradicatethevirus,moreworkisrequiredtobedoneintheaspects oftheidentificationoftheintermediatezoonoticsourcethat causedthetransmissionofthevirustohumans.
Keyfeaturesandentrymechanismofhumancoronaviruses
AllcoronavirusescontainspecificgenesinORF1downstream regionsthatencodeproteinsforviralreplication,nucleocapsid andspikesformation [25].Theglycoproteinspikesontheouter surfaceofcoronavirusesareresponsiblefortheattachmentand entryofthevirustohostcells(Fig.1).Thereceptor-binding domain(RBD)islooselyattachedamongvirus,therefore,thevirus mayinfectmultiplehosts [26,27].Othercoronavirusesmostlyrecognizeaminopeptidasesorcarbohydratesasakeyreceptorfor entrytohumancellswhileSARS-CoVandMERS-CoVrecognize exopeptidases [2].Theentrymechanismofacoronavirusdepends uponcellularproteaseswhichinclude,humanairwaytrypsin-like protease(HAT),cathepsinsandtransmembraneproteaseserine2 (TMPRSS2)thatsplitthespikeproteinandestablishfurtherpenetrationchanges [28,29].MERS-coronavirusemploysdipeptidyl peptidase4(DPP4),whileHCoV-NL63andSARS-coronavirus requireangiotensin-convertingenzyme2(ACE2)asakeyreceptor [2,26]
SARS-CoV-2possessesthetypicalcoronavirusstructurewith spikeproteinandalsoexpressedotherpolyproteins,nucleopro-
teins,andmembraneproteins,suchasRNApolymerase,3chymotrypsin-likeprotease,papain-likeprotease,helicase,glycoprotein,andaccessoryproteins [30,31].Thespikeproteinof SARS-CoV-2containsa3-DstructureintheRBDregiontomaintain thevanderWaalsforces [32].The394glutamineresidueinthe RBDregionofSARS-CoV-2isrecognizedbythecriticallysine31 residueonthehumanACE2receptor [33].Theentiremechanism ofpathogenicityofSARS-CoV-2,fromattachmenttoreplicationis wellmentionedin Fig.3.
GenomicvariationsinSARS-CoV-2
ThegenomeoftheSARS-CoV-2hasbeenreportedover80% identicaltotheprevioushumancoronavirus(SARS-likebatCoV) [34].TheStructuralproteinsareencodedbythefourstructural genes,includingspike(S),envelope(E),membrane(M)andnucleocapsid(N)genes.The orf1ab isthelargestgeneinSARS-CoV-2 whichencodesthepp1abproteinand15nsps.The orf1a gene encodesforpp1aproteinwhichalsocontains10nsps [34–36] Accordingtotheevolutionarytree,SARS-CoV-2liesclosetothe groupofSARS-coronaviruses [37,38] (Fig.5).Recentstudieshave indicatednotablevariationsinSARS-CoVandSARS-CoV-2such astheabsenceof8aproteinandfluctuationinthenumberof aminoacidsin8band3cproteininSARS-CoV-2 [34] (Fig.4).Itis alsoreportedthatSpikeglycoproteinoftheWuhancoronavirus
Fig.3. ThelifecycleofSARS-CoV-2inhostcells;beginsitslifecyclewhenSproteinbindstothecellularreceptorACE2.Afterreceptorbinding,theconformationchangein theSproteinfacilitatesviralenvelopefusionwiththecellmembranethroughtheendosomalpathway.ThenSARS-CoV-2releasesRNAintothehostcell.GenomeRNAis translatedintoviralreplicasepolyproteinspp1aand1ab,whicharethencleavedintosmallproductsbyviralproteinases.Thepolymeraseproduces aseriesofsubgenomic mRNAsbydiscontinuoustranscriptionandfinallytranslatedintorelevantviralproteins.ViralproteinsandgenomeRNAaresubsequentlyassembled intovirionsintheER andGolgiandthentransportedviavesiclesandreleasedoutofthecell.ACE2,angiotensin-convertingenzyme2;ER,endoplasmicreticulum;ERGIC,ER–Golgiintermediate compartment.
ismodifiedviahomologousrecombination.Thespikeglycoprotein ofSARS-CoV-2isthemixtureofbatSARS-CoVandanotknown Beta-CoV [38].Inafluorescentstudy,itwasconfirmedthatthe SARS-CoV-2alsousesthesameACE2(angiotensin-converting enzyme2)cellreceptorandmechanismfortheentrytohostcell whichispreviouslyusedbytheSARS-CoV [39,40].Thesingle N501TmutationinSARS-CoV-2’sSpikeproteinmayhavesignificantlyenhanceditsbindingaffinityforACE2 [33].
Themajorobstacleinresearchprogress
Animalmodelsplayavitalroletouncoverthemechanismsof viralpathogenicityfromtheentrancetothetransmissionand designingtherapeuticstrategies.Previously,toexaminethereplicationofSARS-CoV,variousanimalmodelswereusedwhich showedthesymptomsofsevereinfection [43].Incontrastto SARS-CoV,noMERS-CoVpathogenesiswasobservedinsmallanimals.MicearenotvulnerabletoinfectionbyMERS-coronavirus duetothenon-compatibilityoftheDPP4receptor [44].Asthe entiregenomeofthe2019-novelcoronavirusismorethan80% similartotheprevioushumanSARS-likebatCoV,previouslyused animalmodelsforSARS-CoVcanbeutilizedtostudytheinfectious pathogenicityofSARS-CoV-2.ThehumanACE2cellreceptorisrecognizedbybothSARSandNovelcoronaviruses.Conclusively, TALENorCRISPR-mediatedgeneticallymodifiedhamstersorother smallanimalscanbeutilizedforthestudyofthepathogenicityof novelcoronaviruses.SARS-CoVhasbeenreportedtoreplicateand causeseverediseaseinRats(F344),wherethesequenceanalysis revealedamutationatspikeglycoprotein [45].Thus,itcouldbe
anothersuitableoptiontodevelopspikeglycoproteintargeting therapeuticsagainstnovelcoronaviruses.Recently,micemodels andclinicalisolateswereusedtodevelopanytherapeuticstrategy againstSARS-CoV-2inducedCOVID-19 [46,47].Inasimilarstudy, artificialintelligencepredictionwasusedtoinvestigatetheinhibitoryroleofthedrugagainstSARS-CoV-2 [48].SARS-CoV-2infected patientswerealsousedtoconductrandomizedclinicaltrials [46,49,50].Itisnowimportantthatthescientistsworldwidecollaboratethedesignasuitablemodelandinvestigatetheinvivo mechanismsassociatedwithpathogenesisofSARS-CoV-2.
PotentialtherapeuticstrategiesagainstCOVID-19
Initially,interferons-a nebulization,broad-spectrumantibiotics,andanti-viraldrugswereusedtoreducetheviralload [49,51,52],however,onlyremdesivirhasshownpromisingimpact againstthevirus [53].Remdesivironlyandincombinationwith chloroquineorinterferonbetasignificantlyblockedtheSARSCoV-2replicationandpatientsweredeclaredasclinicallyrecovered [46,50,52].Variousotheranti-viralsarecurrentlybeingevaluatedagainstinfection.Nafamostat,Nitazoxanide,Ribavirin, Penciclovir,Favipiravir,Ritonavir,AAK1,Baricitinib,andArbidol exhibitedmoderateresultswhentestedagainstinfectionin patientsand in-vitro clinicalisolates [46,48,50,52].Severalother combinations,suchascombiningtheantiviralorantibioticswith traditionalChinesemedicineswerealsoevaluatedagainstSARSCoV-2inducedinfectioninhumansandmice [46].Recentlyin Shanghai,doctorsisolatedthebloodplasmafromclinicallyrecoveredpatientsofCOVID-19andinjecteditintheinfectedpatients
M.A.Shereenetal./JournalofAdvancedResearch24(2020)91–98
Fig.4. Betacoronavirusesgenomeorganization;TheBetacoronavirusforhuman(SARS-CoV-2,SARS-CoVandMERS-CoV)genomecomprisesofthe50 -untranslatedregion(50UTR),openreadingframe(orf)1a/b(greenbox)encodingnon-structuralproteins(nsp)forreplication,structuralproteinsincludingspike(blue box),envelop(maroonbox), membrane(pinkbox),andnucleocapsid(cyanbox)proteins,accessoryproteins(lightgrayboxes)suchasorf3,6,7a,7b,8and9bintheSARS-CoV-2genome,andthe30untranslatedregion(30 -UTR).ThedotedunderlinedinredaretheproteinwhichshowskeyvariationbetweenSARS-CoV-2andSARS-CoV.Thelengthofnspsandorfsarenot drawninscale.(Forinterpretationofthereferencestocolourinthisfigurelegend,thereaderisreferredtothewebversionofthisarticle.)
Fig.5. Phylogenetictreeofcoronaviruses(contentinredisthelatestadditionofnewlyemergedSARS-CoV-2andWSFMPWuhan-Hu-1isusedasareferenceinthetree);The phylogenetictreeshowingtherelationshipofWuhan-Hu-1(denotedasred)toselectedcoronavirusisbasedonnucleotidesequencesofthecompletegenome.Theviruses aregroupedintofourgenera(prototypeshown):Alphacoronavirus(skyblue),Betacoronavirus(pink),Gammacoronavirus(green)andDeltacoronavirus(lightblue). Subgroupclustersarelabeledas1aand1bfortheAlphacoronavirusand2a,2b,2c,and2dfortheBetacoronavirus.ThistreeisbasedonthepublishedtreesofCoronavirinae [3,41] andreconstructedwithsequencesofthecompleteRNA-dependentRNApolymerase-codingregionoftherepresentativenovelcoronaviruses(maximumlikelihood methodusingMEGA7.2software).severeacuterespiratorysyndromecoronavirus(SARS-CoV);SARS-relatedcoronavirus(SARSr-CoV);theMiddleEastrespiratory syndromecoronavirus(MERS-CoV);porcineentericdiarrheavirus(PEDV);Wuhanseafoodmarketpneumonia(Wuhan-Hu-1).BatCoVRaTG13Showedhighsequence identitytoSARS-CoV-2 [42].(Forinterpretationofthereferencestocolourinthisfigurelegend,thereaderisreferredtothewebversionofthisarticle.)
whoshowedpositiveresultswithrapidrecovery [54].Inarecent study,itwasidentifiedthatmonoclonalantibody(CR3022)bindswiththespikeRBDofSARS-CoV-2.Thisislikelyduetotheantibody’sepitopenotoverlappingwiththedivergentACE2
receptor-bindingmotif.CR3022hasthepotentialtobedeveloped asatherapeuticcandidate,aloneorincombinationwithother neutralizingantibodiesforthepreventionandtreatmentofCOVID-19infection [55].
VaccinesforSARS-CoV-2
ThereisnoavailablevaccineagainstCOVID-19,whileprevious vaccinesorstrategiesusedtodevelopavaccineagainstSARS-CoV canbeeffective.RecombinantproteinfromtheUrbani(AY278741) strainofSARS-CoVwasadministeredtomiceandhamsters, resultedintheproductionofneutralizingantibodiesandprotectionagainstSARS-CoV [56,57].TheDNAfragment,inactivated wholevirusorlive-vectoredstrainofSARS-CoV(AY278741),significantlyreducedtheviralinfectioninvariousanimalmodels [58–63].DifferentotherstrainsofSARS-CoVwerealsousedtoproduceinactivatedorlive-vectoredvaccineswhichefficiently reducedtheviralloadinanimalmodels.Thesestrainsinclude, Tor2(AY274119) [64,65],Utah(AY714217) [66],FRA(AY310120) [59],HKU-39849(AY278491) [57,67],BJ01(AY278488) [68,69], NS1(AY508724) [70],ZJ01(AY297028) [70],GD01(AY278489) [69] andGZ50(AY304495) [71].However,therearefewvaccines inthepipelineagainstSARS-CoV-2.ThemRNAbasedvaccinepreparedbytheUSNationalInstituteofAllergyandInfectiousDiseasesagainstSARS-CoV-2isunderphase1trial [72].INO-4800DNAbasedvaccinewillbesoonavailableforhumantesting [73] ChineseCentreforDiseaseControlandPrevention(CDC)working onthedevelopmentofaninactivatedvirusvaccine [74,75].Soon mRNAbasedvaccine’ssample(preparedbyStermirnaTherapeutics)willbeavailable [76].GeoVax-BravoVaxisworkingtodevelop aModifiedVaccinaAnkara(MVA)basedvaccine [77].WhileClover Biopharmaceuticalsisdevelopingarecombinant2019-nCoVSproteinsubunit-trimerbasedvaccine [78].
Althoughresearchteamsallovertheworldareworkingto investigatethekeyfeatures,pathogenesisandtreatmentoptions, itisdeemednecessarytofocusoncompetitivetherapeuticoptions andcross-resistanceofothervaccines.Forinstance,thereisapossibilitythatvaccinesforotherdiseasessuchasrubellaormeasles cancreatecross-resistanceforSARS-CoV-2.Thisstatementof cross-resistanceisbasedontheobservationsthatchildreninchina werefoundlessvulnerabletoinfectionascomparedtotheelder population,whilechildrenarebeinglargelyvaccinatedformeasles inChina.
Conclusionandperspective
ThenovelcoronavirusoriginatedfromtheHunanseafoodmarketatWuhan,Chinawherebats,snakes,raccoondogs,palmcivets, andotheranimalsaresold,andrapidlyspreadupto109countries. ThezoonoticsourceofSARS-CoV-2isnotconfirmed,however, sequence-basedanalysissuggestedbatsasthekeyreservoir.DNA recombinationwasfoundtobeinvolvedatspikeglycoprotein whichassortedSARS-CoV(CoVZXC21orCoVZC45)withtheRBD ofanotherBetaCoV,thuscouldbethereasonforcross-species transmissionandrapidinfection.Accordingtophylogenetictrees, SARS-CoVisclosertoSARS-likebatCoVs.Untilnow,nopromising clinicaltreatmentsorpreventionstrategieshavebeendeveloped againsthumancoronaviruses.However,theresearchersareworkingtodevelopefficienttherapeuticstrategiestocopewiththe novelcoronaviruses.Variousbroad-spectrumantiviralspreviously usedagainstinfluenza,SARSandMERScoronaviruseshavebeen evaluatedeitheraloneorincombinationstotreatCOVID-19 patients,micemodels,andclinicalisolates.Remdesivir,Lopinavir, Ritonavir,andOseltamivirsignificantlyblockedtheCOVID-19 infectionininfectedpatients.ItcanbecocludedthatthehomologusrecombinationeventattheSproteinofRBDregionenhanced thetransmissionabilityofthevirus.Whilethedecisionofbring backthenationalsfrominfectedareabyvariouscountriesand poorscreeningofpassengers,becometheleadingcauseofspreadingvirusinotherscountries.
Mostimportantly,humancoronavirusestargetingvaccinesand antiviraldrugsshouldbedesignedthatcouldbeusedagainstthe currentaswellasfutureepidemics.Therearemanycompanies workingforthedevelopmentofeffectiveSARS-CoV-2vaccines, suchasModernaTherapeutics,InovioPharmaceuticals,Novavax, VirBiotechnology,StermirnaTherapeutics,Johnson&Johnson, VIDO-InterVac,GeoVax-BravoVax,CloverBiopharmaceuticals,CureVac,andCodagenix.Butthereisaneedforrapidhumanand animal-basedtrailsasthesevaccinesstillrequire3–10months forcommercialization.Theremustbeacompletebanonutilizing wildanimalsandbirdsasasourceoffood.Besidethedevelopment ofmostefficientdrug,astrategytorapidlydiagnoseSARS-CoV-2in suspectedpatientisalsorequired.Thesignsandsymptomsof SARS-CoV-2inducedCOVID-19areabitsimilartoinfluenzaand seasonalallergies(pollenallergies).Personsufferingfrominfluenzaorseasonalallergymayalsoexhibittempraturewhichcan bedetectedbythermo-scanners,hencethepersonwillbecome suspected.Therefore,anaccurateandrapiddiagnostickitormeter fordetectionofSARS-CoV-2insuspectedpatientsisrequired,as thePCRbasedtestingisexpensiveandtimeconsuming.Different teamsofChinesedoctorsshouldimmediatelysenttoEurpean andothercountries,especiallyspainandItalytocontroltheover spreadofCOVID-19,becauseChinesedoctorshaveefficientlycontrolledtheoutbreakinchinaandlimitedthemortalityratetoless than3%only.ThetherapeuticstrategiesusedbyChinese,should alsobefollowedbyothercountries.
Acknowledgments
TheauthorsacknowledgethePostdoctoralgrantfromTheSecond AffiliatedHospitalofZhengzhouUniversity(forS.K).
DeclarationofCompetingInterest
Theauthorsofthismanuscriptdeclarenoconflictofinterest.
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MuhammadAdnanShereen isaPhDresearcheratWuhanUniversity,workingon Zikavirusandcoronavirusintheaspectsofpathogenesis,drugscreeningand molecularmechanisms.Heisanauthorin8articlespublishedinjournalswith impactfactormorethan5includingtherecentlyacceptedpaperinNaturemicrobiology.
SulimanKhan hascompletedhisPhDdegreefromChineseAcademyofSciences andcurrentlyworkingatsecondaffiliatedhospitalofZhengzhouuniversityas postdoctoralscientist.Hehaspublishedmorethan25articlesand5onSARS-CoV-2 inwellreputedjournalsincludingClinicalmicrobiologyandinfection(CMI)and Journalofclinicalmicrobiology(ASM-JCM)asfirstandcorrespondingauthor.
AbeerKazmi isaPhDstudentatWuhanUniversity.
NadiaBashir isaPhDstudentatWuhanUniversityworkingoncoronaviruses.She isanauthorinmorethan5paperspublishedoracceptedinrenownedjournals.
RabeeaSiddique isaPhDstudentatZhengzhouuniversity.Shehaspublishedmore than10papersinwellreputedjournalsasfirstorcoauthor.
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