Iintlobo ezitsha ze-SARS-CoV-2 (intsholongwane enoxanduva lwe-COVID-19): Ngaba indlela 'ye-Neutralising Antibodies' iyimpendulo kuGuquko oluKhawulezayo?

Iintlobo ezininzi ezintsha ze intsholongwane ziye zavela oko ubhubhane waqala. Ukwahluka okutsha kwaxelwa kwangoko ngoFebruwari ka-2020. Umahluko okhoyo ozise i-UK ukuba ime ngxi kule Krisimesi kuthiwa iyosuleleka ngakumbi nge-70%. Ngokujonga iintlobo ezivelayo, ngaba amayeza amaninzi aphuhliswayo kwihlabathi jikelele asasebenza ngokwaneleyo ngokuchasene nokwahluka okutsha? 'Ukungathathi hlangothi kwe-Antibody' ejolise kwi intsholongwane ibonakala inika ithuba elinika ithemba kule meko yangoku yokungaqiniseki. Imeko yeyokuba ii-antibodies ezisibhozo ezichasene ne-SARS-CoV-2 okwangoku ziphantsi kovavanyo lweklinikhi, kubandakanywa nolingo lwe-'antibody cocktails' olujolise ekoyiseni ukuba kunokwenzeka intsholongwane ukuphuhlisa ukuxhathisa kwi-antibody enye eyenza buthathaka ngokuqokelela iinguqu ezizenzekelayo.

The SARS-selwe-2 intsholongwane unexanduva lokuba Covid-19 Ubhubhani yinxalenye yohlobo lwe-betacoronavirus kusapho lwe-coronaviridae iintsholongwane. lo intsholongwane inoluvo oluhle lwe-RNA genome, oku kuthetha ukuba i-RNA enye i-strand isebenza njengesithunywa se-RNA ngelixa iguqulela ngokuthe ngqo kwiiprotheni zentsholongwane kwi-host host. I-genome ye-SARS-CoV-2 ifaka iiproteni ezine zolwakhiwo {spike (S), imvulophu (E), i-membrane (M), kunye ne-nucleocapsid (N)} kunye ne-16 yeeproteni ezingezizo izinto. Nangona iiprotheni zesakhiwo zidlala indima ekuqapheliseni i-receptor kwi-cell host, i-membrane fusion, kunye nokungena kwentsholongwane elandelayo; iiproteni ezingezizo izakhiwo (NSPs) zidlala indima ebalulekileyo kwimisebenzi yophindaphindo efana ne-RNA polymerization yi-RNA exhomekeke kwi-RNA polymerase (RdRp, NSP12). 

Ngokucacileyo, i-RNA intsholongwane iipolymerase azinawo umsebenzi wokuhlola i-nuclease, oku kuthetha ukuba akukho ndlela ikhoyo yokukhangela iimpazamo ngexesha lokukhutshelwa okanye ukuphindaphinda. Ngoko ke, iintsholongwane Olu sapho lubonisa amazinga aphezulu kakhulu otshintsho okanye uguquko. Oku kuqhuba ukuguquguquka kwegenome kunye nokuvela kwabo ngaloo ndlela kubanika inqanaba eligqithileyo lokuguquguquka kunye nokunceda intsholongwane ukubaleka ukhuselo lomzimba lomkhosi kunye nokuphuhlisa ukuxhathisa ngokuchasene nezitofu zokugonya ^(1,2,3). Ngokucacileyo, ibisoloko iyindalo yeRNA iintsholongwane, kubandakanywa ii-coronavirus ukuba zenzeke kwiinguqu kwi-genome yazo ngamaxabiso aphezulu kakhulu ngalo lonke ixesha ngenxa yezizathu ezichazwe ngasentla. Ezi mpazamo zokuphindaphinda ezinceda i intsholongwane ukoyisa uxinzelelo olubi lokukhetha, kukhokelela ekuhlengahlengisweni kwe intsholongwane. Ekuhambeni kwexesha, ngakumbi izinga lempazamo, ngakumbi ukulungelelanisa. Nangona kunjalo, Covid-19 sisibetho sokuqala esibhaliweyo se-coronavirus kwimbali. Ngubhubhani wesihlanu obhaliweyo ukusukela ngo-1918 umkhuhlane waseSpain; zonke iindyikityha ezine ezibhaliweyo zangaphambili zabangelwa ngumkhuhlane iintsholongwane ⁽⁴⁾.  

Kuyabonakala ukuba, ii-coronavirus zabantu bezisenza utshintsho kwaye ziqhelana nale minyaka ingama-50 idlulileyo. Kubekho oobhubhani abaliqela ukusukela ngo-1966, xa kwarekhodwa isiqendu sokuqala sikabhubhani. Umntu wokuqala obulalayo iintsholongwane ze-Corona Ubhubhani wawungowama-2002 kwiPhondo laseGuangdong, eTshayina owabangelwa yi okwahlukileyo I-SARS-CoV ilandelwa ngubhubhani ka-2012 eSaudi Arabia ngokwahlukileyo kwe-MERS-CoV. Isiqendu sangoku esibangelwe kukwahluka kwe-SARS-CoV-2 yaqala ngoDisemba ka-2019 e-Wuhan, e-China, kwaye emva koko yasasazeka kwihlabathi jikelele yaba sisibetho sokuqala se-coronavirus ekhokelela ekubeni Covid-19 isifo. Ngoku, kukho iintlobo ezininzi ezisezantsi ezisasazwe kumazwekazi ahlukeneyo. I-SARS-CoV-2 ikwabonise usulelo phakathi kwabantu nezilwanyana kunye nokubuyela ebantwini.⁽⁵⁾.

Uphuhliso lwesitofu sokugonya ebantwini intsholongwane ye-Corona yaqala emva kobhubhani ka-2002. Izitofu ezininzi ezichasene ne-SARS-CoV kunye ne-MERS-CoV zaphuhliswa kwaye zenziwa ulingo lwangaphambili kodwa bambalwa abangena kulingo lwabantu. Akukho namnye kubo owafumana imvume ye-FDA nangona kunjalo ⁽⁶⁾. Ezi nzame zibe luncedo kuphuhliso lwesitofu sokugonya ngokuchasene ne-SARS-CoV-2 ngokusetyenziswa kwedatha ekhoyo yangaphambi kweklinikhi kuquka nezo zinxulumene noyilo logonyo olwenziwe ngexesha lophuhliso lwabagqatswa bogonyo lwe-SARS-CoV kunye ne-MERS-CoV. ⁽⁷⁾. Ngeli xesha, kukho izitofu ezininzi zokugonya i-SARS-CoV-2 kwinqanaba eliphezulu kakhulu; ezimbalwa esele zivunyiwe njenge-EUA (Ugunyaziso lokuSebenzisa oluNgxamisekileyo). Malunga nesiqingatha sesigidi sabantu abasemngciphekweni omkhulu e-UK sele befumene iiPfizer's ugonyo lwe-mRNA. Kwaye, nantsi ingxelo esanda kuvela, yosulelo oluphezulu (okanye, i-sub-strain) ye-SARS-CoV-2 e-UK ngeli xesha leKrisimesi. Ibizwa okwexeshana i-VUI-202012/01 okanye i-B117, lo mahluko uneenguqu ezili-17 eziquka enye kwi-spike protein. Ukosuleleka ngakumbi akuthethi ukuba intsholongwane iye yaba yingozi ngakumbi ebantwini. Ngokwendalo, umntu uyazibuza ukuba ezi zitofu zisasebenza ngokwaneleyo na ngokuchasene nokwahluka okutsha. Kuxoxwa ukuba uguqulo olunye kwi-spike akufuneki lwenze ugonyo ('ingingqi ye-spike' ekujoliswe kuyo) lungasebenzi kodwa njengoko iinguqu zisanda ngokuhamba kwexesha, izitofu zokugonya zinokufuna ukulungiswa kakuhle ukuze zivumelane ne-antigenic drift. ^(8,9)

Indlela yokulwa ne-antibody: ugxininiso oluhlaziyiweyo ekuthinteleni izilwa-buhlungu zingafuneka 

Kukule mvelaphi apho 'i-antibody approach' (ibandakanya 'i-antibody engathathi hlangothi ngokuchaseneyo SARS-selwe-2 intsholongwane' kunye 'nezithinteli zonyango ezichaseneyo Covid-19-associated hyperinflammation') ufumana ukubaluleka. Ukungathathi hlangothi kwee-antibodies ngokuchasene ne-SARS-CoV-2 intsholongwane kunye nokwahluka kwayo kunokusebenza 'njengesilungele ukusebenzisa' isixhobo sokuzikhusela.  

The amajoni omzimba Jolisa kwi iintsholongwane ngqo kwinginginya kwaye inokubonelela ngokhuseleko olukhawulezayo ngakumbi kuzo naziphi na iinguqulelo ezisanda kuvela. Le ndlela ayikabonakalisi nkqubela phambili ingako okwangoku kodwa inamandla okujongana nengxaki ye-antigenic drift kunye nokungasebenzi kakuhle kwesitofu sokugonya esivezwa yi-SARS-CoV-2 eguqukayo ekhawulezayo kunye nevelayo. intsholongwane. Ukusukela nge-28 kaJulayi 2020, ii-antibodies ezisibhozo ezichasene ne-SARS-CoV-2 intsholongwane (ezezi LY-CoV555, JS016, REGN-COV2, TY027, BRII-196, BRII-198, CT-P59, kunye ne-SCTA01) beziphantsi kovavanyo lwezonyango. Kwezi zithinteli mzimba zingathathi hlangothi, i-LY-CoV555 i i-antibody ye-monoclonal (mAb). I-VIR-7831, LY-CoV016, BGB-DXP593, REGN-COV2, kunye ne-CT-P59 zezinye izilwa-buhlungu ze-monoclonal ezizamayo njenge-anti-antibodies. I-antibody cocktails inokoyisa nakuphi na ukuxhathisa okunokwenzeka okuphuhliswe ngokuchasene ne-anti-antibody enye, yiyo loo nto ii-cocktails ezifana ne-REGN-COV2, AZD7442, kunye ne-COVI-SHIELD nazo ziphantsi kolingo lwezonyango. Nangona kunjalo, iingxaki zinokukhula ngokuthe ngcembe ukuchasana ne-cocktails ngokunjalo. Ngapha koko, kunokubakho umngcipheko wokwandiswa kwe-antibody-dependent (ADE) ngenxa maqhinga ezibophelela kuphela kwi intsholongwane kwaye abanakukwazi ukuzinciphisa, nto leyo eyenza kube mandundu ukukhula kwesifo ^(10,11). Kuyafuneka ukuqhubeka nomsebenzi wophando olutsha ukulungisa le miba. 

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Inqaku elidibeneyo: I-COVID-19: Iimvavanyo 'ze-Neutralising Antibody' ziqala e-UK

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6. Li Y., Chi W., et al., 2020. Uphuhliso lwesitofu sokugonya iCoronavirus: ukusuka kwi-SARS kunye ne-MERS ukuya kwi-COVID-19. Ijenali yeBiomedical Science volume 27, inombolo yenqaku: 104 (2020). Ipapashwe: 20 December 2020. DOI: https://doi.org/10.1186/s12929-020-00695-2  

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9. BMJ 2020. Iindaba ezimfutshane. I-Covid-19: I-coronavirus entsha ichongiwe e-UK. Ipapashwe nge-16 kuDisemba 2020. DOI: https://doi.org/10.1136/bmj.m4857  

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