Ii-antibodies ezininzi sele zisetyenziswa okanye ziphantsi kophuhliso njengonyango lonyango lwe-COVID-19.Ngokuvela kwezinto ezintsha ezahlukeneyo ze-acute acute respiratory syndrome 2 (SARS-CoV-2), kubalulekile ukuqikelela ukuba basaza kuba sesichengeni sonyango lwe-antibody.Starr et al.Kwasetyenziswa ithala leencwadi leyeast, eliquka zonke iinguqulelo kwi-SARS-CoV-2 receptor dinding domain engayi kuphazamisa kakhulu isibophelelo kwi-host receptor (ACE2), kunye nemephu ukuba ezi zinguqu zichaphazela njani ezintathu. -2 ukubopha amajoni omzimba.La manani achonga uguquko olusinda ekubopheleleni kwe-antibody, kubandakanywa utshintsho olunye olusindayo kwizilwa-buhlungu ezimbini kumxube we-antibody yeRegeneron.Uninzi lweenguqu ezisindayo kwi-antibody enye ziyasasazeka ebantwini.
Ii-Antibodies lunyango olunokubakho kunyango lwe-acute acute respiratory syndrome 2 (SARS-CoV-2), kodwa akucaci ukuba intsholongwane ikhula ukubaleka umngcipheko wabo.Apha, senza imephu ukuba zonke iinguqu kwi-SARS-CoV-2 receptor binding domain (RBD) zikuchaphazela njani ukubophelela kwe-REGN-COV2 cocktail kwi-antibody LY-CoV016.Ezi mephu zipheleleyo ziveze utshintsho lwe-amino acid olubaleke ngokupheleleyo umxube we-REGN-COV2, owenziwe zizilwa-buhlungu ezimbini i-REGN10933 kunye ne-REGN10987 ezijolise kwii-epitopes ezahlukeneyo zolwakhiwo.La manani aphinda achonge utshintsho lwentsholongwane olukhethiweyo kwizigulana ezithe gqolo zosulelo olunyangwa nge-REGN-COV2 nangexesha lokukhetha ukuphuma kwentsholongwane ye-vitro.Okokugqibela, la manani atyhila ukuba iinguqu ezisindayo kwi-antibody enye sele zikhona ekujikelezeni kweentlobo ze-SARS-CoV-2.Ezi mephu zokuphuma ziphelele zinokuchaza iziphumo zotshintsho oluqatshelwe ngexesha lokujongwa kwentsholongwane.
Amajoni omzimba aphuhliswa ukunyanga isifo esibukhali esibukhali sokuphefumla i-coronavirus 2 (SARS-CoV-2) (1).Amajoni omzimba ngokuchasene nezinye iintsholongwane anokwenziwa angasebenzi ngotshintsho lwentsholongwane olukhethiweyo ngexesha lokunyangwa kwezigulana ezosulelekileyo (2, 3) okanye utshintsho lwentsholongwane olusasazeke kwihlabathi jikelele ukunika ukuxhathisa kuyo yonke intsholongwane.Ke ngoko, ukufumanisa ukuba zeziphi iinguqulelo ze-SARS-CoV-2 ezinokubaleka ii-antibodies eziphambili kubalulekile ukuvavanya ukuba utshintsho olubonwe ngexesha lokujongwa kwentsholongwane luchaphazela njani ukusebenza konyango lwe-antibody.
Uninzi lwee-anti-SARS-CoV-2 ezikhokelayo zijolise kwi-viral receptor binding domain (RBD), edibanisa i-angiotensin yokuguqula i-2 (ACE2) receptor (5, 6).Kutshanje, siye savelisa indlela enzulu yokuguqula ukuskena ukwenza imephu ukuba zonke iinguqu ze-RBD zichaphazela njani umsebenzi wayo kunye nokuqatshelwa ngama-antiviral antibodies (7, 8).Indlela ibandakanya ukwenza ithala leencwadi leenguqu ze-RBD, ukuzivakalisa kumphezulu wegwele, kunye nokusetyenziswa kwe-fluorescence-activated cell ukuhlenga kunye nolandelelwano olunzulu ukulinganisa ukuba uguquko ngalunye luchaphazela njani ukusonga kwe-RBD, ukunxulumana kwe-ACE2 (kulinganiswa kuthotho lwetitration), kunye nokubopha i-antibody. (Umfanekiso S1A).Kolu phononongo, sisebenzise ilayibrari ephindaphindayo eguqukileyo echazwe kwi-(7), equlethwe ngokwahlukana kwe-RBD enebhakhowudi, egubungela i-3804 ye-3819 enokwenzeka yokuguqulwa kwe-amino acid.Ithala leencwadi lethu lalungiswa ukusuka kwimvelaphi yemfuza ye-RBD ye-Wuhan-Hu-1 yokuqala.Nangona i-frequency ye-mutants ezininzi iyanda, zisamela ulandelelwano oluqhelekileyo lwe-RBD (9, 10).Sizobe ezimbini zoguqulo luka-2034 olungaphazamisi kakhulu ukusonga kwe-RBD kunye ne-ACE ebopha (7) indlela yokudlula i-REGN-COV2 cocktail (REGN10933 kunye ne-REGN10987) (11, 12) kunye ne-Eli Lilly's LY-CoV016 Ifomu yokuphinda yenzeke i-antibody ichaphazela indlela yokubopha i-antibody (ekwabizwa ngokuba yi-CB6 okanye i-JS016) (13) (Figure S1B).I-REGN-COV2 isandula kunikwa ugunyaziso losetyenziso olungxamisekileyo lwe-COVID-19 (14), ngelixa i-LY-CoV016 okwangoku iphantsi kovavanyo lwezonyango lwesigaba sesi-3 (15).
[Glu406→Trp(E406W)] ubaleke ngamandla kumxube wezilwa-buhlungu ezibini (Umfanekiso 1A).Imephu yokubaleka ye-LY-CoV016 ikwaveze utshintsho oluninzi lokubaleka kwiindawo ezahlukeneyo kwi-RBD (Umfanekiso 1B).Nangona ezinye iinguqulelo zokubaleka zinokuphazamisa amandla e-RBD okuzibophelela kwi-ACE2 okanye ukuvakalisa ngendlela egoqwe ngokufanelekileyo, ngokwemilinganiselo yangaphambili yokuskena okunzulu kusetyenziswa igwele-ebonisa i-RBD, iinguqulelo ezininzi ezisebenzayo zinempembelelo encinci okanye ayinazo kwezi zinto zisebenzayo (7 ) (Umfanekiso we-1, u-A kunye no-B ubonisa ukulahlekelwa kwe-ACE2, ngelixa i-Figure S2 ibonisa ukuhla kwe-RBD expression.
(A) Ukwenza imephu ye-antibody kwi-REGN-COV2.Igrafu yomgca esekhohlo ibonisa ukubaleka kwisiza ngasinye kwi-RBD (isimbuku sazo zonke iinguqu kwisiza ngasinye).Umfanekiso welogo ekunene ubonisa indawo eyomeleleyo yokubalekela (umgca omfusa ngaphantsi).Ubude bonobumba ngamnye bulingana namandla okuphunyuka okulamlwa lutshintsho lwe-amino acid, kwaye "inqaku lokubaleka" le-1 kwinguqulelo nganye lihambelana nokubaleka ngokupheleleyo.Isikali se-y-axis sahlukile kumqolo ngamnye, ngoko ke, umzekelo, i-E406W ibaleka kuzo zonke izilwa-buhlungu ze-REGN, kodwa ibonakala kakhulu kwii-cocktails kuba yonganyelwe zezinye iisayithi zokuphuncuka kwezilwa-buhlungu ezizimeleyo.Kuguqulelo olunokwehla, i-S2, A kunye no-B, zisetyenziselwa ukufaka imibala kwimephu ngendlela iinguqulelo eziyichaphazela ngayo intetho ye-RBD esongwayo.I-S2, i-C kunye ne-D zisetyenziselwa ukusasaza impembelelo kubudlelwane be-ACE2 kunye nokubonakaliswa kwe-RBD phakathi kwazo zonke iinguqulelo ezibonwe ekujikelezeni kweentsholongwane.(B) Njengoko kubonisiwe ku-(A), zoba i-LY-CoV016.(C) Sebenzisa i-spike-pseudotyped lentiviral particles ukuqinisekisa ukuguqulwa kwezinto eziphambili kwi-neutralization assay.Sikhethe ukuqinisekisa uguquko oluqikelelwa ukuba lunempembelelo enkulu okanye lubekho ngamaxesha amaninzi kwii-SARS-CoV-2 zodwa (ezinje nge-N439K) kujikelezo.Inqaku ngalinye limele ukunyuka kwe-fold inhibitory concentration (IC50) yokuguqulwa kwenguqu ehambelana nencopho ye-wild-type (WT) engaguqukiyo equlethe i-D614G.Umgca ohlaza okwesibhakabhaka ohlaza okwesibhakabhaka we-1 ubonisa impembelelo yokungathathi hlangothi efana ne-WT, kunye nexabiso> i-1 ibonisa ukunyuka kwe-neutralization.Umbala wechaphaza ubonisa ukuba uyafuna na ukuphuma kwimephu.Amachaphaza abonisa ukuba ekubeni i-IC50 ingaphandle koluhlu lwe-dilution olusetyenzisiweyo, utshintsho oluninzi luyajongwa (umda ophezulu okanye ophantsi).Uninzi lweenguqu eziguqukayo zivavanywa ngokuphindwe kabini, ngoko ke kukho amanqaku amabini.I-curve epheleleyo ye-neutralization iboniswe kuMfanekiso 2. S3.Izishunqulelo ezinobumba omnye weentsalela ze-amino acid zilandelayo: A, Ala;C, iCysteine;D, Asp;E, Glu;F, Phe;G, Gly;H, eyakhe;Mna, Ile;K, ilysine;L, uLiu;iMetropolis N, Assen;P, iPro;Q, Gln;R, Arg;S, Ser;T, Thr;V, Val;W, itryptophan;kunye noY, Tyr.
Ukuze siqinisekise impembelelo ye-antigenic yeenguqu eziphambili, senze uvavanyo lwe-neutralization sisebenzisa i-panicle pseudotyped lentiviral particles, kwaye safumanisa ukuba kukho ukuhambelana phakathi kwemephu yokuphunyuka kwe-antibody kunye ne-neutralization assay (Figure 1C kunye ne-Figure S3).Njengoko bekulindelekile kwimephu ye-antibody ye-REGN-COV2, uguquko kwindawo engama-486 luthatyathelwa bucala yi-REGN10933, ngelixa uguqulo olukwizikhundla ezingama-439 kunye ne-444 luthatyathelwa bucala yi-REGN10987, ke olu tshintsho alunakubaleka.Kodwa i-E406W yaphuncuka kwezi zithinteli zimbini ze-REGN-COV2, ngoko ke iphinde yasinda kumxube ngamandla.Ngohlalutyo lwesakhiwo kunye nokukhetha ukubaleka kwentsholongwane, uRegeneron ukholelwa ukuba akukho tshintsho lwe-amino acid enye inokuphuncuka kwizilwa-buhlungu ezimbini kwi-cocktail (11, 12), kodwa imephu yethu epheleleyo ichonga i-E406W njengotshintsho lwe-cocktail.I-E406W ichaphazela i-antibody ye-REGN-COV2 ngendlela ethile, kwaye ayiphazamisi kakhulu umsebenzi we-RBD, kuba inciphisa kancinci isiphumo sokungathathi hlangothi kwe-LY-CoV016 (Figure 1C) kunye ne-titer yamasuntswana elentiviral e-spiked (Figure). S3F).
Ukuphonononga ukuba ingaba imephu yethu yokuphunyuka iyahambelana nokuvela kweentsholongwane phantsi kokhetho lwe-antibody, siqale sajonga idatha yovavanyo lokubalekela intsholongwane yeRegeneron, apho intetho ye-spike yakhuliswa kwinkcubeko yeseli phambi kwayo nayiphi na i-REGN10933 I-vesicular. stomatitis virus (VSV), REGN10987 okanye REGN-COV2 cocktail (12).Lo msebenzi uchonge utshintsho oluhlanu lokubaleka ukusuka kwi-REGN10933, iinguqulelo ezimbini zokubaleka ezivela kwi-REGN10987, kwaye akukho zinguqu kwi-cocktail (Umfanekiso 2A).Ukuguqulwa okukhethiweyo kuzo zonke iinkcubeko ezisixhenxe zeeseli kugxininiswe kwimephu yethu yokuphunyuka, kunye notshintsho lwe-nucleotide enye ye-codon yasendle kwi-Wuhan-Hu-1 RBD ngokulandelelana nayo iyafikeleleka (Figure 2B), ebonisa umahluko phakathi kokuphunyuka kwe-Concordance. igrafu kunye nokuvela kwentsholongwane phantsi koxinzelelo lwe-antibody kwinkcubeko yeeseli.Kuyafaneleka ukuba uqaphele ukuba i-E406W ayinakufikeleleka ngotshintsho olulodwa lwe-nucleotide, enokuthi ichaze ukuba kutheni i-Regeneron cocktail ekhethiweyo ayikwazi ukuyichonga nangona ukunyamezela okulungileyo kwe-RBD ukugoqa kunye ne-ACE2 affinity.
(A) Ubukho be-antibodies, i-Regeneron isebenzisa i-panicle pseudotype VSV ukukhetha ukuguqulwa kwentsholongwane yokuphunyuka kwinkcubeko yeseli (12).(B) Umzobo wokuphunyuka, njengoko kubonisiwe kuMfanekiso 1A, kodwa ubonisa kuphela utshintsho olufikelelekayo ngotshintsho olulodwa lwe-nucleotide kwi-Wuhan-Hu-1 ngokulandelelana.I-non-gray ibonisa ukuguqulwa kwenkcubeko yeseli (obomvu), kunye nezigulane ezisulelekileyo (blue) ), okanye zombini (ezimfusa).Umzobo we-S5 ubonisa ezi grafu, ezinemibala ngendlela iinguqu ezichaphazela ngayo i-ACE2 affinity okanye i-RBD expression.(C) I-Kinetics yokuguqulwa kwe-RBD kwizigulane eziphathwe nge-REGN-COV2 ngomhla we-145th wosulelo (umgca onamachaphaza amnyama).Ukuphindaphinda koqhagamshelo phakathi kwe-E484A kunye ne-F486I kunyukile, kodwa ekubeni i-E484A ingeyonguquko yokuphuncuka kumzobo wethu, ayiboniswa kwezinye iiphaneli.Bona kwakhona umfanekiso.S4.(D) Utshintsho lokubaleka olwenzeka kwinkcubeko yeeseli kunye nezigulana ezosulelekileyo ziyafikeleleka nge-nucleotide enye, kwaye ukubotshwa kwezilwa-buhlungu zokubaleka akubangeli naziphi na iindleko ezinkulu kwi-ACE2 affinity [njengoko ilinganiswe ngendlela yokubonisa igwele (7)].Inqaku ngalinye liyinguqu, kwaye imilo yayo kunye nombala ibonisa ukuba inokufumaneka kwaye ikhethwe ngexesha lokukhula kwentsholongwane.Awona manqaku angasekunene kwi-x-axis abonisa ukubaleka okunamandla okubopha isilwa-mntu esikhuselayo;amanqaku aphezulu kwi-y-axis abonisa ubudlelwane obuphezulu be-ACE2.
Ukumisela ukuba ingaba i-Escape Atlas inokuhlalutya na ukuvela kweentsholongwane ezosulela abantu, sivavanye idatha yolandelelwano olunzulu olusuka kwisigulana esithe safumana i-REGN-COV2 ngomhla we-145 emva kokufunyaniswa koNyango lwe-COVID-19 (16).Unyango lwasemva kwexesha luvumela inani lentsholongwane yesigulana ukuba liqokelele iyantlukwano yemfuza, ezinye zazo ezinokuqhutywa luxinzelelo lwe-immune, kuba isigulana sinobuthathaka bokusabela kwe-antibody phambi konyango (16).Emva kokulawulwa kwe-REGN-COV2, ukuphindaphinda kweenguqu ezintlanu ze-amino acid kwi-RBD zatshintsha ngokukhawuleza (Umfanekiso 2C kunye noMzobo S4).Imephu yethu yokuphunyuka ibonise ukuba ezintathu kwezi nguqulelo zibaleke REGN10933 kwaye enye yasinda REGN10987 (Figure 2B).Kuyaphawuleka ukuba emva konyango lwe-antibody, ayizizo zonke iinguqu eziye zatshintshelwa kwindawo emiselweyo.Ngokuchasene noko, kukho ukunyuka nokuwa kokhuphiswano (Umfanekiso 2C).Lo mzekelo uye wabonwa kwinguqu yangaphakathi yeenginginya eziguqukayo zezinye iintsholongwane (17, 18), mhlawumbi ngenxa yokhuphiswano phakathi kofuzo oluhamba ngokukhululekileyo kunye nomgca wentsholongwane.Zombini ezi mikhosi zibonakala zidlala indima kwizigulane ezinosulelo oluzingileyo (Figure 2C kunye neFigure S4C): E484A (hayi ukuguquka kokuphunyuka kumzobo wethu) kunye ne-F486I (ukubalekela i-REGN10933) ukuhamba ngokukhululekile emva konyango, kunye nemigca yentsholongwane ephethe i-N440D Kwaye I-Q493K (ebaleka i-REGN10987 kunye ne-REGN10933, ngokulandelanayo) yaqala yakhuphisana ne-REGN10933 yokubalekela i-mutant Y489H, emva koko yakhuphisana nomnombo ophethe i-E484A kunye ne-F486I kunye ne-Q493K.
Ezintathu kwezine zotshintsho lwezigulana ezinyangwa nge-REGN-COV2 azikhange zichongwe kukhetho lwentsholongwane yeRegeneron yentsholongwane (Umfanekiso 2B), obonisa inzuzo yemephu epheleleyo.Ukhetho lwentsholongwane aluphelelanga kuba banokuchonga kuphela naluphi na utshintsho olukhethwe ngokungakhethiyo kuloo mfuniselo wenkcubeko yeseli.Ngokuchasene noko, imephu epheleleyo ichaza zonke iinguqu, ezinokuthi zibandakanye utshintsho olubangelwa izizathu ezingahambelani nonyango, kodwa luchaphazela ngengozi ukubopha i-antibody.
Ngokuqinisekileyo, ukuvela kweentsholongwane kuchaphazeleka kukuthintelwa kokusebenza kunye noxinzelelo lokuphepha izilwa-buhlungu.Iinguqu kunye nezigulana ezikhethiweyo kwinkcubeko yeeseli zihlala zihlangabezana nale migaqo ilandelayo: zibaleka ukubopha i-antibody, zinokungena ngotshintsho olunye lwe-nucleotide, kwaye zineendleko ezincinci okanye zingabikho kwaukubakho kwi-ACE2 affinity [ngotshintsho olunzulu lwangaphambili olubonakaliswe kusetyenziswa iYeast Scanning measurement RBD (7 )] (Umfanekiso 2D kunye noMzobo S5).Ke ngoko, imephu epheleleyo yendlela iinguqu ezichaphazela ngayo i-phenotypes ye-biochemical engundoqo ye-RBD (efana ne-ACE kunye ne-antibody binding) ingasetyenziselwa ukuvavanya iindlela ezinokwenzeka zokuvela kwentsholongwane.Enye i-caveat kukuba kwixesha elide lokuziphendukela kwemvelo, njengoko kubonwa kwintsholongwane yentsholongwane kunye nokuphunyuka kweziyobisi, ngenxa yokusebenzisana kwe-epistatic, indawo yokunyamezela ukuguqulwa kwenguqu ingatshintsha (19-21).
Imephu epheleleyo isivumela ukuba sivavanye utshintsho olukhoyo lokubaleka kwi-SARS-CoV-2 ejikelezayo.Sijonge zonke ii-SARS-CoV-2 ezifumanekayo zabantu ngokulandelelana ukusukela nge-11 kaJanuwari, 2021 kwaye safumanisa ukuba inani elikhulu lotshintsho lwe-RBD luphunyukile kwisithinteli-ntsholongwane esinye okanye ngaphezulu (Umfanekiso 3).Nangona kunjalo, ekuphela kwenguquko yokusinda ekhoyo kwi >0.1% yolandelelwano yi REGN10933 escape mutant Y453F [0.3% yolandelelwano;bona (12)], REGN10987 ukubaleka mutant N439K [1.7% yolandelelwano;bona iSazobe 1C kunye (22)], kunye ne-LY-CoV016 yokuguqula i-K417N (0.1% ulandelelwano; bona kwakhona uMfanekiso 1C).I-Y453F inxulumene nokuqhambuka okuzimeleyo okunxulumene neefama zemink eNetherlands naseDenmark (23, 24);kuyaphawuleka ukuba ulandelelwano lwe-mink ngokwalo ngamanye amaxesha luqulethe ezinye iinguqu zokubalekela, ezifana ne-F486L (24).I-N439K ithandwa kakhulu eYurophu, kwaye yenza inxalenye enkulu yolandelelwano oluvela eSkotlani nase-Ireland eYurophu (22, 25).I-K417N ikhona kumnombo we-B.1.351 owafunyanwa okokuqala eMzantsi Afrika (10).Olunye ukuguqulwa kwenkxalabo yangoku yi-N501Y, ekhoyo kwi-B.1.351 kunye nakwi-B.1.1.7 yomnombo ochongwe ekuqaleni e-UK (9).Imephu yethu ibonisa ukuba i-N501Y ayinasiphumo kwi-REGN-COV2 antibody, kodwa isiphumo esiphakathi kuphela kwi-LY-CoV016 (Umfanekiso 3).
Kwindibaniselwano ye-antibody okanye i-antibody nganye, ukusukela nge-11 kaJanuwari, phakathi kwe-317,866 yomgangatho ophezulu wokulandelelana kwe-SARS-CoV-2 ethathwe ngumntu kwi-GISAID (26), ubudlelwane phakathi kwamanqaku okubaleka kutshintsho ngalunye kunye nokuphindaphinda.Iphawulwe.I-REGN-COV2 cocktail yokuphunyuka kwenguquko ye-E406W ifuna utshintsho oluninzi lwe-nucleotide kulandelelwano lwe-Wuhan-Hu-1 RBD, kwaye ayijongwa kulandelelwano lwe-GISAID.Olunye uguquko lwentsalela E406 (E406Q kunye ne-E406D) lujongwe ngokubalwa kwamaza aphantsi, kodwa ezi zi-amino acids eziguqukayo azikho iinguquko ze-nucleotide enye kude ne-W.
Njengoko kulindelekile, ukuguqulwa kotshintsho lwenzeka rhoqo kwi-antibody-RBD interface.Nangona kunjalo, ulwakhiwo lulodwa alwanelanga ukuqikelela ukuba zeziphi iinguqulelo ezilawula ukusinda.Umzekelo, i-LY-CoV016 isebenzisa amatyathanga ayo anzima kwaye alula ukubophelela kwi-epitope ebanzi ewela umphezulu wokubopha i-ACE2, kodwa inkqubo yokuphunyuka ibandakanya iinguqu kwiintsalela ze-RBD kwikhonkco elinzima lokumisela ukuhambelana kommandla (Umfanekiso 4A kunye noMzobo S6, E ukuya G).Ngokwahlukileyo koko, ukubaleka kwe-REGN10933 kunye ne-REGN10987 kwenzeka ikakhulu kwiintsalela ze-RBD ezipakishwe kujongano lwe-antibody enzima kunye namatyathanga alula (Umfanekiso 4A kunye noMzobo S6, A ukuya ku-D).Utshintsho lwe-E406W olusindileyo kumxube we-REGN-COV2 lwenzeka kwiintsalela ebezingadibani ne-antibody (Umfanekiso 4, A no-B).Nangona i-E406 ikufutshane ngokwesakhiwo kwi-LY-CoV016 (umzobo 4B kunye noMzobo S6H), uguqulo lwe-E406W lunempembelelo encinci kakhulu kwi-antibody (Umfanekiso 1, B kunye no-C), ebonisa ukuba indlela ethile yolwakhiwo olude luchasene ne-REGN. - I-antibody ye-COV2 (Figure S6I).Isishwankathelo, iinguqu kwiintsalela ze-RBD ekudibaneni nezilwa-buhlungu azisoloko zilamla ukubaleka, kwaye ezinye iinguqulelo ezibalulekileyo zokuphunyuka zenzeka kwiintsalela ezingadibani nezilwa-buhlungu (Umfanekiso 4B kunye noMzobo S6, D kunye no-G).
(A) Umzobo wokubaleka oqikelelweyo kwisakhiwo se-RBD esibotshelelwe sisikhuselo somzimba.[REGN10933 kunye ne-REGN10987: I-Protein Database (PDB) ID 6XDG (11);LY-CoV016: PDB ID 7C01 (13)].Iindawo eziguquguqukayo zemixokelelwane enzima kunye nekhaphukhaphu ye-antibody iboniswa njengeekhathuni ezibhlowu, kwaye umbala okumphezulu we-RBD ubonisa amandla okuphuncuka kokuguqulwa kwenguqu kwesi siza (umhlophe ubonisa ukuba akukho kuphuncuka, kwaye ubomvu bubonisa olona lunamandla. indawo yokubalekela i-antibody okanye umxube) .Iisayithi ezingasebenziyo zitshintshwa zibe ngwevu.(B) Kwi-antibody nganye, hlela isayithi njengodibano lwe-antibody oluthe ngqo (ii-athom ezingezizo eze-hydrogen ngaphakathi kwe-4Å ye-antibody), isilwa-ntsholongwane se-anti-proximal (4 ukuya ku-8Å) okanye isilwa-ntsholongwane se-antibody (> 8Å).Inqaku ngalinye limele indawo, eyahlulwe yaba kuphuncuka (bomvu) okanye ukungaphumi (kumnyama).Umgca odayiweyo ongwevu umele ixabiso elibalulekileyo elisetyenziselwa ukwahlula isiza njengokubaleka okanye ukungaphumi (ukufumana iinkcukacha, jonga iiMathiriyeli kunye neeNdlela).Amanani abomvu namnyama abonisa ukuba zingaphi iisayithi kudidi ngalunye ezibalekileyo okanye ezingaphunywanga.
Kolu phononongo, senze imephu ngokupheleleyo yeenguqu ezibaleka ezo zi-anti-SARS-CoV-2 antibodies.Ezi mephu zibonisa ukuba uphawu lwangaphambili lotshintsho lwenguqu alugqibekanga.Akukho nalunye uguquko lwe-amino acid olunokuthi lubaleke izilwa-buhlungu ezimbini kwi-cocktail ye-REGN-COV2 ezichongiwe, kwaye azichongi uninzi lwezigulana ezizingileyo zosulelo olunyangwa nge-cocktail.inguquko.Ewe kunjalo, imephu yethu ayikawuphenduli owona mbuzo ucinezelayo: Ngaba i-SARS-CoV-2 iya kukhula ukumelana nezi zithinteli-gazi?Kodwa into eqinisekileyo yeyokuba iyakhathaza into yokuba uninzi lweenguquko zokubaleka zinefuthe elincinane kwi-RBD yokusonga okanye i-receptor affinity, kwaye sele kukho utshintsho olukwinqanaba elisezantsi kwiintsholongwane ezijikelezayo.Ekugqibeleni, kuyafuneka ukuba ulinde kwaye ujonge ukuba loluphi utshintsho oluya kuhanjiswa yi-SARS-CoV-2 xa isasazeka phakathi kwabantu.Umsebenzi wethu uya kunceda "uqwalaselo" ngokuchaza ngokukhawuleza impembelelo yokuguqulwa kwenguqu ehlelwe yi-viral genome surveillance.
Eli linqaku elivulekileyo lokufikelela lisasazwe phantsi kwemiqathango yeLayisensi ye-Creative Commons Attribution.Inqaku livumela ukusetyenziswa okungathintelwanga, ukuhanjiswa, kunye nokuveliswa kwakhona kuyo nayiphi na indlela phantsi komqathango wokuba umsebenzi wokuqala ucatshulwe ngokufanelekileyo.
Qaphela: Sikucela kuphela ukuba usinike idilesi ye-imeyile ukuze umntu omcebisayo kwiphepha azi ukuba ufuna ukubona i-imeyile kwaye ayingospam.Asiyi kubamba naziphi na iidilesi ze-imeyile.
Lo mbuzo usetyenziselwa ukuvavanya ukuba ngaba ungumtyeleli kwaye uthintele ukuthunyelwa kwe-spam okuzenzekelayo.
Tyler N.Starr, Allison J.Greaney, Amin Addetia, William W. Hannon, Manish C. Choudhary (Manish C. Choudhary), Adam S. Dinges (Adam S.
Imephu epheleleyo yotshintsho lwe-SARS-CoV-2 olubaleka umxube we-Regeneron monoclonal antibody inceda ukuchaza ukuvela kwentsholongwane ekunyangeni izigulana.
Tyler N.Starr, Allison J.Greaney, Amin Addetia, William W. Hannon, Manish C. Choudhary (Manish C. Choudhary), Adam S. Dinges (Adam S.
Imephu epheleleyo yotshintsho lwe-SARS-CoV-2 olubaleka umxube we-Regeneron monoclonal antibody inceda ukuchaza ukuvela kwentsholongwane ekunyangeni izigulana.
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Ixesha lokuposa: Feb-24-2021