Izinhlobo Ezintsha Ze-SARS-CoV-2 (igciwane elibhekele i-COVID-19): Ingabe Indlela 'Ye-Neutralising Antibodies' ingaba Yimpendulo Yokuguquka Okusheshayo?

Izinhlobo eziningi ezintsha ze- igciwane zivele selokhu kwaqala lolu bhubhane. Okuhlukile okusha kwabikwa ngoFebhuwari 2020. Okuhlukile kwamanje okumise i-UK kulo Khisimusi kuthiwa kuzotheleleka ngo-70%. Uma kubhekwa izinhlobo ezisafufusa, ingabe imithi yokugoma eminingana eyenziwa emhlabeni wonke isazosebenza ngokwanele ngokumelene nezinhlobonhlobo ezintsha futhi? 'I-Neutralising Antibody' indlela eqondiswe ku- igciwane kubonakala ukunikeza inketho enethemba kulesi simo samanje sokungaqiniseki. Isimo ukuthi amasosha omzimba ayisishiyagalombili avimbela i-SARS-CoV-2 njengamanje ahlolwa, okubandakanya izivivinyo 'zama-antibody cocktails' okuhloswe ngawo ukunqoba ukuthi kungenzeka igciwane ukuthuthukisa ukumelana ne-antibody eyodwa enciphisa ngokuqoqa ukuguqulwa okuzenzakalelayo.

The SARS selwe-2 igciwane unomthwalo we Covid-19 Ubhubhane luyingxenye yohlobo lwe-betacoronavirus emndenini we-coronaviridae amagciwane. Lokhu igciwane ine-genome ye-RNA yomqondo omuhle, okusho ukuthi umucu owodwa i-RNA isebenza njenge-RNA yesithunywa kuyilapho ihumusha ngokuqondile kumaprotheni egciwane kumsingathi. I-genome ye-SARS-CoV-2 ifaka amaphrotheni amane esakhiwo {spike (S), imvilophu (E), ulwelwesi (M), kanye ne-nucleocapsid (N)} kanye namaprotheni ayi-16 angewona awesakhiwo. Ngenkathi amaprotheni esakhiwo edlala indima ekuqaphelisweni kwe-receptor kuseli eliphethe, i-membrane fusion, kanye nokungena kwegciwane okulandelayo; ama-non-structural proteins (NSPs) adlala indima ebalulekile emisebenzini yokuphindaphinda efana ne-RNA polymerization yi-RNA encike ku-RNA polymerase (RdRp, NSP12). 

Ngokuphawulekayo, i-RNA igciwane ama-polymerase awanawo umsebenzi wokuhlola ukuhlolwa kwe-nuclease, okusho ukuthi ayikho indlela etholakalayo yokuhlola amaphutha ngesikhathi sokuloba noma ukuphindaphinda. Ngakho-ke, amagciwane zalo mndeni zibonisa amanani aphezulu kakhulu okuhlukahluka noma ukuguqulwa. Lokhu kushayela ukuhlukahluka kwe-genome kanye nokuziphendukela kwemvelo ngaleyo ndlela kubanikeze izinga elidlulele lokuguquguquka nokusiza igciwane ukubalekela ukungatheleleki komsingathi kanye nokuthuthukisa ukumelana nemithi yokugoma ^(1,2,3). Ngokusobala, bekulokhu kuyimvelo ye-RNA amagciwane, okuhlanganisa nama-coronavirus ukuthi ashintshe ku-genome yawo ngamanani aphezulu kakhulu ngaso sonke isikhathi ngenxa yezizathu ezishiwo ngenhla. Lawa maphutha okuphindaphinda asiza i igciwane nqoba ingcindezi yokukhetha engalungile, kuholele ekuzivumelaniseni nezimo igciwane. Ngokuhamba kwesikhathi, izinga lamaphutha liyanda, ukujwayela kuyanda. Nokho, Covid-19 ubhubhane lwe-coronavirus lokuqala olubhalwe phansi emlandweni. Ubhadane lwesihlanu olubhalwe phansi kusukela ngomkhuhlane waseSpain wango-1918; zonke izifo eziwubhadane ezibhalwe ngaphambili ezine zadalwa umkhuhlane amagciwane ⁽⁴⁾.  

Ngokusobala, ama-coronavirus abantu abelokhu akha izinguquko futhi azivumelanisa nezimo kule minyaka engama-50 edlule. Kube nezifo eziningi eziwubhubhane kusukela ngo-1966, lapho kuqoshwa isiqephu sokuqala sobhubhane. Umuntu wokuqala obulalayo Ama-coronavirus Ubhubhane lwalungo-2002 esifundazweni sase-Guangdong, eChina olwadalwa yi- okufana I-SARS-CoV ilandelwa ubhubhane lwango-2012 eSaudi Arabia ngokuhlukile kwe-MERS-CoV. Isiqephu samanje esidalwe ngenxa yokuhluka kwe-SARS-CoV-2 saqala ngoDisemba 2019 eWuhan, eChina, sabe sesibhebhetheka emhlabeni wonke saba ubhubhane lokuqala lwe-coronavirus oluholela ekutheni Covid-19 isifo. Manje, kunezinhlobonhlobo ezincane ezimbalwa ezisabalele kuwo wonke amazwekazi ahlukene. I-SARS-CoV-2 iphinde yakhombisa ukudluliswa kwezinhlobo zezilwane phakathi kwabantu nezilwane futhi ibuyela kubantu⁽⁵⁾.

Ukwakhiwa komuthi wokugomela umuntu i-coronavirus yaqala ngemuva kobhubhane luka-2002. Imithi yokugomela eminingana emelene ne-SARS-CoV kanye ne-MERS-CoV yathuthukiswa futhi yenziwa izivivinyo zangaphambi komtholampilo kodwa bambalwa abangena ezivivinyweni zabantu. Akekho noyedwa kubo owathola imvume ye-FDA ⁽⁶⁾. Le mizamo ibe usizo ekuthuthukisweni kokugomela i-SARS-CoV-2 ngokusebenzisa idatha ekhona yangaphambi kokwelashwa okuhlanganisa naleyo ehlobene nokwakhiwa komgomo owenziwe ngesikhathi sokuthuthukiswa kwabantu abazogomela i-SARS-CoV kanye ne-MERS-CoV. ⁽⁷⁾. Kuleli qophelo lesikhathi, kunemithi eminingi yokugomela i-SARS-CoV-2 esesigabeni esithuthuke kakhulu; ambalwa asevele avunyiwe njenge-EUA (Ukugunyazwa Kokusetshenziswa Kwezimo Eziphuthumayo). Cishe isigamu sesigidi sabantu abasengcupheni enkulu e-UK asebewatholile ama-Pfizer's umuthi wokugomela i-mRNA. Futhi, nangu umbiko wohlobo olusha olusanda kuvela, oluthelelanayo kakhulu (noma, uhlobo oluncane) lwe-SARS-CoV-2 e-UK ngalesi sikhathi sikaKhisimusi. Iqanjwe okwesikhashana i-VUI-202012/01 noma i-B117, lokhu okuhlukile kunokuguquguquka okungu-17 okuhlanganisa nokukodwa kuphrotheni ye-spike. Ukutheleleka okuningi akusho ukuthi igciwane isibe yingozi kakhulu kubantu. Ngokwemvelo, umuntu uyazibuza ukuthi ingabe le mithi yokugoma isazosebenza ngokwanele yini ngokumelene nezinhlobonhlobo ezintsha futhi. Kuphikiswana ngokuthi ukuguqulwa okukodwa ku-spike akufanele kwenze imithi yokugoma ('isifunda se-spike') ingasebenzi kodwa njengoba ukuguqulwa kunqwabelana ngokuhamba kwesikhathi, imithi yokugoma ingase idinge ukulungiswa kahle ukuze ivumelane nokukhukhuleka kwe-antigenic. ^(8,9)

Indlela ye-antibody: ukugcizelela okuvuselelwe kokuqeda amasosha omzimba kungase kudingeke 

Kungalesi sizinda lapho 'indlela ye-antibody' (efaka 'i-neutralizing antibodies ngokumelene nayo SARS selwe-2 igciwane' kanye 'namasosha omzimba okwelapha ngokumelene Covid-19-associated hyperinflammation') izuza ukubaluleka. Amasosha omzimba angathathi hlangothi ngokumelene ne-SARS-CoV-2 igciwane futhi okuhlukile kwakho kungase kusebenze 'njengesilungele ukusetshenziswa' ithuluzi lokugomela elingenzi lutho.  

The ukuqeda ama-antibodies target the amagciwane ngqo kumsingathi futhi anganikeza ukuvikeleka okusheshayo ikakhulukazi kunoma yikuphi okuhlukile okusanda kuvela. Lo mzila awukabonisi inqubekelaphambili eningi okwamanje kodwa unamandla okubhekana nenkinga yokukhukhuleka kwe-antigenic kanye nokungahle kube nokungafani komuthi wokugoma okwethulwa i-SARS-CoV-2 eguqukayo nethuthukayo. igciwane. Kusukela ngomhla zingama-28 kuJulayi 2020, amasosha omzimba ayisishiyagalombili avimbela i-SARS-CoV-2 igciwane (okungukuthi i-LY-CoV555, JS016, REGN-COV2, TY027, BRII-196, BRII-198, CT-P59, kanye ne-SCTA01) bezihlolwa ngomtholampilo. Kulawa ma-antibodies angathathi hlangothi, i-LY-CoV555 iyi- I-monoclonal antibody (mAb). I-VIR-7831, LY-CoV016, BGB-DXP593, REGN-COV2, kanye ne-CT-P59 amanye amasosha omzimba angama-monoclonal azamayo njengamasosha omzimba aqeda amandla. Ama-antibody cocktail anganqoba noma yikuphi ukumelana okungaba khona okuthuthukiswe ngokumelene ne-antibody eyodwa engathathi hlangothi, yingakho ama-cocktail afana ne-REGN-COV2, AZD7442, ne-COVI-SHIELD nawo asahlolwa ngomtholampilo. Kodwa-ke, izinhlobo zingase zithuthukise ukumelana nama-cocktails futhi. Ngaphezu kwalokho, kungase kube nengozi yokuthuthukisa i-antibody-dependent (ADE) ngenxa ama-antibodies lokho kuhlanganisa kuphela igciwane futhi abakwazi ukuziqeda, ngaleyo ndlela babhebhethekise ukukhula kwesifo ^(10,11). Kudingeka ukuqhubeka komsebenzi wocwaningo olusha ukuze kubhekwane nalezi zinkinga. 

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I-athikili ehlobene: I-COVID-19: Izilingo 'ze-Neutralising Antibody' Ziqala e-UK

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