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Xitsongwatsongwana xa Khorona

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Xitsongwatsongwana xa Khorona i ntlawa wa switsongwatsongwana swa RNA leswi yelanaka leswi vangaka mavabyi eka swihadyana leswi mamisaka na swinyanyana. Eka vanhu na swinyanyana, swi va nga mavabyi ya swirho swo hefemula leswi nga sukaka eka leswi nga nyawuriki ku ya eka leswi dlayaka. Mavabyi yo olova eka vanhu ya katsa timhangu tin’wana ta mukhuhlwana lowu tolovelekeke (lowu tlhelaka wu vangiwa hi switsongwatsongwana swin’wana, ngopfungopfu tirhinovirus ), kasi tinxaka leti dlayaka swinene ti nga vanga SARS, MERS na COVID-19 . Eka tihomu na tinguluve swi vanga ku pfimba ka khwiri, kasi eka timbeva swi vanga hepatitis na encephalomyelitis.

Xitsongatsongwana xa khorona xi vumba ndyangu lowutsongo wa Orthocoronavirinae, eka ndyangu wa Coronaviridae, odara ya Nidovirales na realm Riboviria . [1] I switsongwatsongwana leswi funengetiweke leswi nga na genome ya RNA ya single-stranded ya positive-sense na nucleocapsid ya helical symmetry. [2] Vukulu bya genome bya xitsongatsongwana xa khorona byi sukela eka kwalomu ka 26 kuya eka 32 kilobases, yin’wana ya letikulu eka RNA virus. [3] Ti ni swipikiri leswi nga ni xivumbeko xa xibakele leswi humaka ehenhla ka tona, leswi eka swifaniso leswitsongo swa tielektroni swi endlaka xifaniso lexi tsundzuxaka hi corona ya tinyeleti, leyi vito ra tona ri humaka eka xona. [4]

Matumbulukelo

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Vito ra "xitsongatsongwana xa khorona" ri huma eka Xilatini corona, leswi vulaka "harhi" kumbe "xirhendzevutani", hi roxe i ku lomba eka Xigriki κορώνη</link> korṓnē, "xirhabyana, xirhangiso". Vito leri ri tumbuluxiwile hi June Almeida na David Tyrrell lava nga sungula ku languta na ku dyondza hi xitsongatsongwana xa khorona ya vanhu. [5] Rito leri ri tirhisiwile ro sungula eku kandziyisiweni hi 1968 hi ntlawa lowu nga riki wa xivumbeko wa vativi va switsongwatsongwana eka magazini lowu nge Nature ku vula ndyangu lowuntshwa wa switsongwatsongwana. [4] Vito leri ri vula xivumbeko xa xihlawulekisi xa virions (xivumbeko lexi tluleriwaka xa xitsongwatsongwana) hi electron microscopy, leyi nga na fringe ya ti bulbous surface projections letikulu, bulbous surface projections leti endlaka xifaniso lexi tsundzuxaka solar corona kumbe halo. [4] [5] Xivumbeko lexi xi endliwa hi ti viral spike peplomers, leti nga tiphurotheni leti nga ehenhla ka xitsongwatsongwana. [6]

Vito ra sayense ra xitsongatsongwana xa khorona ri amukeriwile tanihi vito ra muxaka hi International Committee for the Nomenclature of Viruses (endzhaku yi thyiwile International Committee on Taxonomy of Viruses ) hi 1971. [7] Loko nhlayo ya tinxaka letintshwa yi andza, muxaka lowu wu avanyisiwile hi tinxaka ta mune, ku nga Alphaxitsongatsongwana xa khorona, Betaxitsongatsongwana xa khorona, Deltaxitsongatsongwana xa khorona, na Gammaxitsongatsongwana xa khorona hi 2009. [8] Vito leri tolovelekeke ra xitsongatsongwana xa khorona ri tirhisiwa ku kombetela eka xirho xin'wana na xin'wana xa ndyangu lowutsongo wa Orthocoronavirinae . [1] Kusukela hi 2020, 45 wa tinxaka ti amukeriwile ximfumo.

Matimu

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Swiviko swo sungula swa ku tluleriwa hi xitsongatsongwana xa khorona eka swifuwo swi humelerile eku heleni ka malembe ya va 1920s, loko ku humelela vuvabyinyana bya mahefemulele ya tihuku leti fuyiweke eNorth America. [9] Arthur Schalk na MC Hawn hi 1931 va endlile xiviko xo sungula xa vuxokoxoko lexi hlamuseleke ku tluleriwa lokuntshwa ka ku hefemula ka tihuku eNorth Dakota . Ku tluleriwa ka swinyanyana leswi ha ku velekiwaka swi tiveka hi ku hefemula na ku pfumala ku tsakela laha ku nga na nhlayo ya le henhla ya mafu ya 40–90%. [10] Leland David Bushnell na Carl Alfred Brandly va hambanisile xitsongwatsongwana lexi nga vanga ku tluleriwa hi 1933. [11] Kutani xitsongwatsongwana lexi a xi tiviwa tanihi infectious bronchitis virus (IBV). Charles D. Hudson na Fred Robert Beaudette va byale xitsongwatsongwana lexi ro sungula hi 1937. Xikombiso lexi xi sungule ku tiveka tanihi muxaka wa Beaudette. Eku heleni ka malembe ya va 1940s, ku kumiwile mixaka yin'wana iyimbirhi ya xitsongatsongwana xa khorona ya swiharhi, JHM leyi vangaka mavabyi ya byongo (murine encephalitis) na mouse hepatitis virus (MHV) leyi vangaka hepatitis eka timbeva. [12] A swi nga xiyiwi hi nkarhi wolowo leswaku switsongwatsongwana leswi swinharhu swo hambana swa yelana. [7]

Xitsongatsongwana xa khorona xa vanhu xi kumiwile hi malembe yava 1960s [13] [14] hi ku tirhisa tindlela timbirhi to hambana eUnited Kingdom nale United States. [15] E. C. Kendall, Malcolm Bynoe, na David Tyrrell lava tirhaka eka Common Cold Unit ya British Medical Research Council va hlengeletile xitsongwatsongwana xo hlawuleka xa common cold lexi thyiweke B814 hi 1961. [16] [17] [18] Xitsongwatsongwana lexi a xi nga ta byariwa hi ku tirhisa tithekiniki ta ntolovelo leti nga byala hi ku humelela ti rhinoviruses, adenoviruses na tivhayirasi tin’wana leti tivekaka ta mikhuhlwana leyi nga toloveleka. Hi 1965, Tyrrell na Bynoe va hlakulele xitsongwatsongwana lexi xa novhele hilaha ku humelelaka hi ku xi hundzisela hi ku landzelelana eka ndhavuko wa swirho swa trachea ya embryo ya munhu . [19] Ndlela leyintshwa yo byala yi nghenisiwile eka lab hi Bertil Hoorn. [20] Xitsongwatsongwana lexi hambanisiweke loko xi cheriwa hi nomu eka vatirhi vo tirhandzela xi vange xirhami naswona xi nga tirhi hi ether leswi kombisaka leswaku xi na mvhilopho ya lipid . [16] [21] Dorothy Hamre na John Procknow eYunivhesiti ya Chicago va hambanise xirhami xa novhele eka swichudeni swa vutshunguri hi 1962. Va hambanise ni ku kurisa xitsongwatsongwana lexi eka ndhavuko wa tinyama ta tinsu, va xi thya 229E. Xitsongwatsongwana xa novhele xi vange xirhami eka vatirhi vo tirhandzela naswona, ku fana na B814, xi nga tirhi hi ether. [22]

Mutivi wa switsongwatsongwana wa le Scotland June Almeida eXibedlhele xa St Thomas eLondon, hi ku tirhisana na Tyrrell, u pimanisile swivumbeko swa IBV, B814 na 229E hi 1967. [23] Hi ku tirhisa electron microscopy switsongwatsongwana leswinharhu swi kombisiwile swi ri leswi yelanaka hi xivumbeko hi xivumbeko xa swona xo angarhela na swipikiri leswi hambaneke leswi fanaka na swibakele . [24] Ntlawa wa ndzavisiso eka National Institute of Health hi lembe leri fanaka wu kotile ku hambanyisa xirho xin’wana xa ntlawa lowu wuntshwa wa switsongwatsongwana hi ku tirhisa organ culture naswona wu thye yin’wana ya tisampulu ta vito ra OC43 (OC for organ culture). [25] Kufana na B814, 229E, na IBV, xitsongwatsongwana xa novhele xa cold OC43 axiri na swipikiri swo hlawuleka swofana na club loko swi langutiwa hi electron microscope. [26]

Switsongwatsongwana swo tumbuluka swa mikhuhlwana leswi fanaka na IBV swi hatle swi kombisiwile kuva na swona swi fambelana hi xivumbeko na xitsongwatsongwana xa mouse hepatitis. [12] Ntlawa lowu wuntshwa wa switsongwatsongwana wu thyiwile vito ra xitsongatsongwana xa khorona endzhaku ka xivumbeko xa tona xo hlawuleka xa xivumbeko. [4] Xitsongwatsongwana xa vanhu xa xitsongatsongwana xa khorona 229E na xitsongwatsongwana xa vanhu xa xitsongatsongwana xa khorona OC43 swiyile emahlweni swi dyondziwa eka makume ya malembe lawa yanga landzela. [27] [28] Muxaka wa xitsongwatsongwana xa xitsongatsongwana xa khorona B814 wu lahlekile. A swi tiveki leswaku a ku ri xitsongwatsongwana xa sweswi xa vanhu xa xitsongatsongwana xa khorona xihi. [29] Kusukela kwalano ku tiviwile ti xitsongatsongwana xa khorona tin’wana ta vanhu, ku katsa na SARS-CoV hi 2003, HCoV NL63 hi 2003, HCoV HKU1 hi 2004, MERS-CoV hi 2013, na SARS-CoV-2 hi 2019. [30] Kutlhele kuva na nhlayo leyikulu ya ti xitsongatsongwana xa khorona ta swiharhi leti tivekaka kusukela hi malembe yava 1960s. [31]

Xivumbeko

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Xitsongatsongwana xa khorona xa naparticles letikulu, leti nga na xirhendzevutani leti nga na tindhawu to hlawuleka. [32] Vukulu bya tona byi cinca cinca swinene laha ti diameters ta xikarhi ta 80 ku ya eka 120 nm . Vukulu byo tlula mpimo bya tiveka kusuka eka 50 kuya eka 200 nm hi vukulu. [33] Nhlayo hinkwayo ya timolekhuli hi xiringaniso i 40 000 kDa . Ti pfaleriwile eka mvhilopho leyi nghenisiweke hi timolekhuli to hlayanyana ta tiphrotheyini. [34] Mvhilopho ya lipid bilayer, ti protein ta membrane na nucleocapsid swisirhelela xitsongwatsongwana loko xiri ehandle ka sele ya host. [35]

Mvhilopho ya xitsongwatsongwana yi endliwe hi lipid bilayer laha tiphurotheni ta xivumbeko xa membrane (M), envelope (E) na spike (S) ti khomiweke. [36] Molar ratio ya E:S:M eka lipid bilayer yi kwalomu ka 1:20:300. [37] Proteyini ya E na M i tiphuritheni ta xivumbeko leti hlanganisiweke na lipid bilayer ku vumba mvhilopho ya xitsongwatsongwana na ku hlayisa vukulu bya yona. [38] Ti protein ta S ta laveka eka ku tirhisana na ti cells leti amukelaka. Kambe xitsongatsongwana xa khorona ya vanhu NL63 yi hlawulekile hikuva protein ya yona ya M yina ndzhawu yo boha sele ya host, naswona ku n gari protein ya yona ya S. [39] Diameter ya mvhilopho i 85 nm. Mvhilopho ya xitsongwatsongwana eka ti electron micrographs yi humelela tani hi mpatswa lowu hambaneke wa ti electron-dense shells (swikhegelo leswinga vonakiki ngopfu eka electron beam leyi tirhisiwaka ku scan xiphemu xa xitsongwatsongwana). [40] [38]

Phuroteyini ya M i phurotheni leyikulu ya xivumbeko xa mvhilopho leyi nyikaka xivumbeko hinkwaxo naswona i phrotheyini ya muxaka wa III ya membrane . Yi na 218 kuya eka 263 wa masalela ya amino acid naswona yi endla leyara ya 7.8 nm yo tiya. [34] Yi na tidomeni tinharhu, ectodomain yo koma ya N-terminal, domain ya transmembrane leyi hlanganisaka kanharhu, na endodomain ya C-terminal. Domain ya C-terminal yi endla lattice yofana na matrix leyi engetelaka eka extra-thickness ya mvhilopho. Tinxaka tohambana hambana tingava na N - kumbe O -linked glycans eka protein amino-terminal domain ya tona. Proteyini ya M i ya nkoka swinene hi nkarhi wa nhlengeletano, budding, ku vumbiwa ka mvhilopho, na switeji swa pathogenesis swa xirhendzevutani xa vutomi bya xitsongwatsongwana. [41]

Ti protein ta E i ti protein letintsongo ta xivumbeko naswona ti cinca cinca swinene eka tinxaka tohambana hambana. [33] Kuna ntsena kwalomu ka 20 wa tikopi ta molecule ya protein ya E eka xiphemu xa xitsongatsongwana xa khorona. [37] Va 8.4 ku ya eka 12 kDa hi vukulu naswona ti vumbiwa hi 76 kuya eka 109 wa ti amino acids. [33] I ti protein ta nkoka (i.e. leti nghenisiweke eka lipid layer) naswona tina ti domain timbirhi kunga transmembrane domain na extramembrane C-terminal domain. Ti lava kuva ti α-helical hiku hetiseka, na domain yin’we ya α-helical transmembrane, naswona ti endla ti pentameric (ntlhanu-molecular) ion channels eka lipid bilayer. Ti na vutihlamuleri eka nhlengeletano ya virion, ku xavisiwa ka tisele endzeni ka tisele na morphogenesis (budding). [34]

Ti spikes hi tona leti hambanisaka ngopfu ti xitsongatsongwana xa khorona naswona tina vutihlamuleri eka vuandlalo byofana na corona kumbe halo. Hi xiringaniso xiphemu xa xitsongatsongwana xa khorona xi na 74 wa swipikiri swa le henhla. [42] Xipikiri xin’wana ni xin’wana xi kwalomu ka 20 nm yo leha naswona yi vumbiwa hi trimer ya S tiphrotheyini. Phurotheyini ya S hi hala tlhelo yi vumbiwa hi xiphemu lexitsongo xa S1 na S2 . Xivumbeko xa homotrimeric xa S protein i class I fusion protein leyi hlanganisaka ku bohiwa ka receptor na membrane fusion exikarhi ka xitsongwatsongwana na host cell. Subunit ya S1 yi vumba nhloko ya spike naswona yina receptor-binding domain (RBD). Subunit ya S2 yi endla nsinya lowu khomaka spike eka mvhilopho ya xitsongwatsongwana naswona eka protease activation swiendla leswaku kuva na fusion. Ti subunits timbirhi titshama tihlanganisiwile hi noncovalently loko tiri karhi ti paluxiwa eka vuandlalo bya xitsongwatsongwana kufikela loko ti namarhela eka host cell membrane. [34] Eka xiyimo lexi tirhaka hi ndlela yo tirha, S1 tinharhu ti khomanisiwile na ti subunits timbirhi ta S2. Subunit complex yi avanyisiwile hi ti subunits ha yin’we loko xitsongwatsongwana xi boha no hlangana na host cell ehansi ka xiendlo xa ti proteases tofana na ndyangu wa cathepsin na transmembrane protease serine 2 (TMPRSS2) ya host cell. [43]

Ti protein ta S1 hi tona swiphemu swa nkoka swinene eka ku tluleriwa. Nakambe i swiphemu leswi cinca-cincaka swinene tani hileswi swinga na vutihlamuleri eka host cell specificity. Ti na ti domain timbirhi letikulu leti thyiweke N-terminal domain (S1-NTD) na C-terminal domain (S1-CTD), leti havumbirhi bya tona ti tirhaka tani hi ti receptor-binding domains. Ti NTDs ti lemuka naku boha chukele ehenhla ka sele ya host. Lexi nga riki kona i MHV NTD leyi bohaka eka molekhuli ya ku namarhela ka sele leyi fambelanaka na antijeni ya tiphrotheyini ya carcinoembryonic 1 (CEACAM1). S1-CTDs yina vutihlamuleri byo lemuka ti protein receptors tohambana hambana tofana na angiotensin-converting enzyme 2 (ACE2), aminopeptidase N (APN), na dipeptidyl peptidase 4 (DPP4). [34]

Ntlawa lowutsongo wa ti xitsongatsongwana xa khorona (ngopfu-ngopfu swirho swa ntlawa lowutsongo wa betaxitsongatsongwana xa khorona A ) na wona wu na phrotheyini yo koma ya le henhla leyi fanaka na spike leyi vuriwaka hemagglutinin esterase (HE). [31] Ti protein ta HE ti humelela tani hi ti homodimers leti vumbiweke hi kwalomu ka 400 wa masalela ya amino acid naswona tina 40 kuya eka 50 kDa hi vukulu. Ti vonaka tani hi swiphemu leswintsongo swa le henhla swa 5 kuya eka 7 nm yo leha yi nghenisiwile exikarhi ka swipikiri. Ti pfuneta eka ku namarhela na ku hambana na sele leyi amukelaka. [44]

Endzeni ka mvhilopho, ku na nucleocapsid, leyi vumbiwaka kusuka eka tikopi to tala ta protein ya nucleocapsid (N), leti bohiweke eka genome ya positive-sense single-stranded RNA eka conformation ya muxaka wa vuhlalu -on-a-string leyi yaka emahlweni. [38] [45] N protein i phosphoprotein ya 43 kuya eka 50 kDa hi vukulu, naswona yi avanyisiwile hi tidomeni tinharhu leti hlayisiweke. Vunyingi bya tiphrotheyini byi vumbiwa hi ti- domain 1 na 2, leti hi ntolovelo ti fuweke hi ti- arginine ni ti- lysine . Domain 3 yina makumu yo koma ya carboxy terminal naswona yina net negative charge hikokwalaho ka ku tlula mpimo ka acidic eka masalela ya basic amino acid. [33]

Genome ya xitekela

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SARS-CoV genome na tiphrotheyi

Ti xitsongatsongwana xa khorona ti na positive-sense, single-stranded RNA genome. Vukulu bya genome ya ti xitsongatsongwana xa khorona byi sukela eka 26.4 ku ya eka 31.7 kilobases . [3] Vukulu bya genome i byin’wana bya lebyikulu eka switsongwatsongwana swa RNA. Genome yina 5′ methylated cap na 3′ polyadenylated ncila . [38]

Nhlangano wa genome ya xitsongwatsongwana xa corona i 5′-murhangeri-UTR -replicase (ORF1ab)-spike (S)-mvhilopho (E)-membrane (M)-nucleocapsid (N)- 3′UTR -poly (A) ncila. Tifureme to hlaya leti pfulekeke 1a na 1b, leti tekaka swiphemu swimbirhi eka nharhu swosungula swa genome, ti khoda replicase polyprotein (pp1ab). Polyprotein ya replicase yi tihambanisa ku endla 16 wa ti protein leti nga riki ta xivumbeko (nsp1–nsp16). [38]

Tifureme to hlaya ta le ndzhaku ti khoda tiphrotheyini ta mune letikulu ta xivumbeko: spike, envelope, membrane, na nucleocapsid . [46] Ku hlanganisiwa exikarhi ka tifureme leti to hlaya ku na tifureme to hlaya ta tiphrotheyini leti pfunetaka. Nhlayo ya ti accessory proteins na ntirho wa tona swihlawulekile kuya hi xitsongatsongwana xa khorona yokarhi. [38]

Ku nghena ka sele

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Ku tluleriwa ku sungula loko protein ya viral spike yi namarhela eka complementary host cell receptor ya yona. Endzhaku ka ku namarhela, protease ya sele ya muhaxi ya hambanisiwa naswona yi endla leswaku protein ya spike leyi khomaneke na receptor yi tirha. Kuya hi protease ya sele ya muhaxi leyi kumekaka, ku hambanisiwa na ku tirhisiwa swi pfumelela xitsongwatsongwana ku nghena eka sele ya muhaxi hi endocytosis kumbe ku hlanganisiwa hi ku kongoma ka mvhilopho ya xitsongwatsongwana na membrane ya muhaxi . [47]

  1. ↑ 1.0 1.1 Empty citation (help) 
  2. ↑ . Cherry J, Demmler-Harrison GJ, Kaplan SL, Steinbach WJ, Hotez PJ.  Missing or empty |title= (help)
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  29. ↑ Coronaviruses, p. 199–223, "The other OC strains and B814 that could not be adapted to mouse brain resisted adaptation to cell culture as well; these distinct viruses have since been lost and may actually have been rediscovered recently" 
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  31. ↑ 31.0 31.1 Susan Baker (virologist), 806–28. de Groot RJ, Baker SC, Baric R, Enjuanes L, Gorbalenya AE, Holmes KV, Perlman S, Poon L, Rottier PJ, Talbot PJ, Woo PC, Ziebuhr J.  Missing or empty |title= (help)
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