Masoja ekudzivirira chirwere akati wandei atove kushandiswa kana pasi pekuvandudzwa senzira dzekurapa dzeCOVID-19.Nekubuda kwezvitsva zvakasiyana-siyana zveakanyanya acute kufema chirwere coronavirus 2 (SARS-CoV-2), zvakakosha kufanotaura kana vachizoramba vachibatwa nemishonga inorwisa mabhakitiriya.Starr et al.Yakashandiswa raibhurari yembiriso, iyo inovhara zvese shanduko muSARS-CoV-2 receptor binding domain iyo isingazokanganisa zvakanyanya kusungirira kune host receptor (ACE2), uye mepu kuti aya machinjiro anokanganisa sei matatu Iwo makuru anti-SARS-CoV. -2 antibody kusunga.Nhamba idzi dzinoratidza shanduko dzinopukunyuka dzinosunga masoja ekudzivirira chirwere, kusanganisira shanduko imwe chete inopukunyuka masoja ekudzivirira chirwere ari mumusanganiswa weRegeneron antibody.Machinjiro mazhinji anotiza masoja ekudzivirira chirwere ari kupararira muvanhu.
Masoja ekudzivirira chirwere anogona kurapa kweakanyanya acute kufema chirwere coronavirus 2 (SARS-CoV-2), asi hazvisi pachena kuti hutachiona hunokura kutiza njodzi yavo.Pano, isu tinomepu machinjiro ese ari muSARS-CoV-2 receptor binding domain (RBD) anokanganisa sei kusungwa kweREGN-COV2 cocktail kune antibody LY-CoV016.Aya mamepu akazara akaburitsa amino acid shanduko yakanzvenga zvachose musanganiswa weREGN-COV2, uyo unoumbwa nemasoja maviri ekudzivirira chirwere REGN10933 uye REGN10987 anonangisa akasiyana epitopes.Nhamba idzi dzinoratidzawo shanduko dzehutachiona dzakasarudzwa muvarwere vanoramba vaine hutachiona vanorapwa neREGN-COV2 uye panguva yekusarudzwa kwehutachiona hwehutachiona.Chekupedzisira, manhamba aya anoratidza kuti shanduko dzinotiza antibody imwe dzatovepo mukutenderera SARS-CoV-2 strains.Aya mamepu ekupukunyuka akazara anogona kutsanangura mhedzisiro yekuchinja kunoonekwa panguva yekutarisa hutachiona.
Masoja ekudzivirira chirwere ari kugadzirwa kurapa akanyanya acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (1).Masoja ekudzivirira chirwere anorwisa mamwe mavhairasi anogona kuitwa kusashanda nehutachiona shanduko yakasarudzwa panguva yekurapa kwevarwere vane hutachiona (2, 3) kana mavhairasi ekuchinja akapararira pasirese kuti ape kuramba hutachiona hwese.Naizvozvo, kuona kuti ndeipi SARS-CoV-2 shanduko inogona kutiza masoja ekudzivirira chirwere kwakakosha kuti uongorore kuti shanduko dzinoonekwa panguva yekutarisa hutachiona dzinokanganisa sei kushanda kweantibody therapy.
Mazhinji anotungamira anti-SARS-CoV-2 masoja ekudzivirira ekudzivirira anotarisa hutachiona receptor binding domain (RBD), iyo inopindirana inosunga kune angiotensin inoshandura enzyme 2 (ACE2) receptor (5, 6).Munguva pfupi yapfuura, takagadzira yakadzika shanduko yekuongorora nzira yekumepu machinjiro ese eRBD anokanganisa basa rayo uye kucherechedzwa neantiviral antibodies (7, 8).Iyo nzira inosanganisira kugadzira raibhurari yeRBD mutants, kuaburitsa pamusoro pembiriso, uye kushandisa fluorescence-yakagadziriswa maseru kurongedza uye yakadzika sequencing kuti uone kuti imwe neimwe shanduko inobata sei RBD kupeta, ACE2 affinity (yakayerwa mumutsara wetitration), uye antibody inosunga. (Mufananidzo S1A).Muchidzidzo ichi, takashandisa raibhurari inodzokororwa inotsanangurwa mu (7), iyo inoumbwa nebarcoded RBD akasiyana, inovhara 3804 ye3819 inogoneka amino acid shanduko.Raibhurari yedu yakagadziridzwa kubva kuRBD genetic kumashure kwekutanga yega Wuhan-Hu-1.Kunyangwe kuwanda kwematanti akati wandei kuri kuwedzera, ivo vachiri kumiririra yakajairika RBD kutevedzana (9, 10).Isu takadhirowa maviri e2034 shanduko isingakanganise kupeta kweRBD uye ACE inosunga (7) nzira yekupfuura iyo REGN-COV2 cocktail (REGN10933 uye REGN10987) (11, 12) uye Eli Lilly's LY-CoV016 Iyo recombinant fomu ye masoja ekudzivirira chirwere anokanganisa nzira yekusunga masoja ekudzivirira chirwere (inonziwo CB6 kana JS016) (13) (Mufananidzo S1B).REGN-COV2 ichangobva kupihwa mvumo yekushandisa yekukurumidzira yeCCIDID-19 (14), nepo LY-CoV016 parizvino iri kuita chikamu chechitatu chekiriniki miedzo (15).
[Glu406→Trp(E406W)] yapukunyuka zvakasimba musanganiswa wemasoja maviri ekudzivirira chirwere (Mufananidzo 1A).Mepu yekupukunyuka yeLY-CoV016 yakaratidzawo akawanda ekutiza shanduko panzvimbo dzakasiyana muRBD (Mufananidzo 1B).Kunyangwe mamwe machinjiro ekutiza anogona kukanganisa kugona kweRBD kusunga kuACE2 kana kutaura nenzira yakapetwa zvakafanira, zvinoenderana nezviyero zvakapfuura zveyakadzama mutation scanning uchishandisa mbiriso-inoratidzwa RBD, mazhinji ekuchinja anoshanda ane zvishoma kana kusave nemhedzisiro pazvinhu izvi zvinoshanda. ) (Mufananidzo 1, A uye B unomiririra kurasikirwa kweACE2 affinity, nepo Mufananidzo S2 inomiririra kuderera kweRBD kutaura.
(A) Kugadzira antibody muREGN-COV2.Girafu yemutsara kuruboshwe inoratidza kutiza panzvimbo yega yega muRBD (huwandu hwekuchinja kwese panzvimbo yega yega).Mufananidzo welogo kurudyi unoratidza nzvimbo yakasimba yekutiza (yepepuru underline).Kureba kwemavara ega ega kunoenzana nesimba rekupunyuka kunoyananiswa neamino acid mutation, uye “kupukunyuka mamakisi” kwe1 pakuchinja kwega kwega kunoenderana nekupukunyuka kwakazara.Chikero chey-axis chakasiyana pamutsetse wega wega, saka, semuenzaniso, E406W inopukunyuka masoja ekudzivirira eREGN ese, asi zvinonyanya kuoneka kune majoka nekuti inokurirwa nedzimwe nzvimbo dzekutiza dzemasoja ega ega.Kune iyo scalable vhezheni, S2, A uye B, anoshandiswa kupendesa mepu nemabatirwo anoita shanduko pakutaura kweRBD yakapetwa.S2, C uye D inoshandiswa kugovera pesvedzero paACE2 affinity uye RBD kutaura pakati pekuchinja kwese kunoonekwa mukutenderera kwehutachiona.(B) Sezvinoratidzwa mu (A), dhirowa LY-CoV016.(C) Shandisa spike-pseudotyped lentiviral particles kuti uone kuchinja kwakakosha mune neutralization assay.Isu takasarudza kuonesa shanduko dzinofungidzirwa kuve nemhedzisiro yakakura kana kuvepo nepamusoro-soro muSARS-CoV-2 yakaparadzana (senge N439K) mukutenderera.Imwe neimwe pfungwa inomiririra kuwedzera kwakapetwa kweiyo median inhibitory concentration (IC50) yekuchinja kunoenderana nepamusoro peiyo unmutated wild-type (WT) ine D614G.Mutsara webhuruu wakadhindwa mutsara 1 unomiririra mhedzisiro yakafanana neWT, uye kukosha> 1 inomiririra yakawedzera kushomeka kuramba.Ruvara rwedoti runoratidza kana uchida kutiza kubva pamepu.Iwo madotsi anoratidza kuti sezvo IC50 iri kunze kweiyo dilution yakatevedzana inoshandiswa, iyo yakawanda shanduko inotariswa (yepamusoro kana yakaderera muganho).Mazhinji mutants anoedzwa mune duplicate, saka pane mapoinzi maviri.Iyo yakazara neutralization curve inoratidzwa muMufananidzo 2. S3.Madimburiso ebhii rimwe chete amino acid asara ndeaya anotevera: A, Ala;C, Cysteine;D, Asp;E, Glu;F, Phe;G, Gly;H, wake;Ini, Ile;K, lysine;L, Liu;Metropolis N, Assen;P, Pro;Q, Gln;R, Arg;S, Ser;T, Thr;V, Val;W, tryptophan;uye Y, Tyr.
Kuti tione maantigenic mhedzisiro yekuchinja kukuru, takaita assay yekusagadzikana tichishandisa panicle pseudotyped lentiviral particles, uye takaona kuti paive nekusawirirana pakati peiyo antibody inosunga kutiza mepu uye neutralization assay (Mufananidzo 1C uye Mufananidzo S3).Sezvinotarisirwa kubva kuREGN-COV2 antibody mepu, shanduko iri pachinzvimbo 486 inongogadziriswa neREGN10933, ukuwo shanduko pazvinzvimbo 439 uye 444 inongogadziriswa neREGN10987, saka shanduko idzi hadzigone kutiza.Asi E406W yakapukunyuka maviri masoja ekudzivirira chirwere eREGN-COV2, saka yakapukunyukawo musanganiswa zvine simba.Kuburikidza nekuongorora kwemaitiro uye kusarudzwa kwekupukunyuka kwehutachiona, Regeneron anotenda kuti hapana kana amino acid imwe chete shanduko inogona kutiza masoja ekudzivirira chirwere ari mujoka (11, 12), asi mepu yedu izere inoratidza E406W seyekupunyuka mutation.E406W inobata iyo REGN-COV2 antibody neimwe nzira, uye haikanganise zvakanyanya basa reRBD, nekuti inongo deredza zvishoma mhedzisiro yeLY-CoV016 (Mufananidzo 1C) uye titer ye spiked pseudotyped lentiviral particles (Mufananidzo. S3F).
Kuti tiongorore kana mepu yedu yekutiza inoenderana nekushanduka kwemavhairasi pasi pekusarudzwa kweantibody, takatanga tatarisa iyo data yeRegeneron virus yekutiza sarudzo yekuyedza, umo izwi rekuti spike rakakurira musero tsika pamberi pechero REGN10933 The vesicular. stomatitis virus (VSV), REGN10987 kana REGN-COV2 cocktail (12).Iri basa rakaratidza shanduko shanu dzekupukunyuka kubva kuREGN10933, shanduko mbiri dzekupukunyuka kubva kuREGN10987, uye hapana shanduko kubva kucocktail (Mufananidzo 2A).Iko shanduko dzakasarudzwa nesesesero nomwe tsika dzinoratidzwa mumepu yedu yekutiza, uye shanduko imwe chete-nucleotide yemusango-mhando codon muWuhan-Hu-1 RBD kutevedzana inowanikwawo (Mufananidzo 2B), zvichiratidza mutsauko pakati pekupukunyuka Concordance. graph uye hutachiona shanduko pasi pekumanikidzwa kweantibody mune cell tsika.Izvo zvakakosha kuti tizive kuti E406W haigone kuwanikwa neamwechete nucleotide shanduko, izvo zvinogona kutsanangura kuti sei Regeneron cocktail sarudzo isingakwanise kuizivisa kunyangwe kushivirira kwakanaka kweRBD kupeta uye ACE2 hukama.
(A) Muhupo hwemasoja ekudzivirira chirwere, Regeneron anoshandisa panicle pseudotype VSV kusarudza hutachiona hunopukunyuka shanduko musero tsika (12).(B) Dhiagiramu yekupukunyuka, sezvakaratidzwa muMufananidzo 1A, asi inongoratidza shanduko dzinowanikwa neiyo imwe nucleotide shanduko muWuhan-Hu-1 kutevedzana.Kusina-grey kunoratidza kuchinja kwesero tsika (tsvuku), uye varwere vane utachiona (bhuruu)), kana zvose (pepuru).Mufananidzo S5 inoratidza magirafu aya, ane mavara nemabatiro anoita shanduko kuACE2 affinity kana RBD kutaura.(C) Kinetics yeRBD mutation muvarwere vanobatwa neREGN-COV2 pazuva re145th rehutachiona (black dotted vertical line).Kuwanda kwekubatanidza pakati peE484A neF486I kwakawedzera, asi sezvo E484A isiri shanduko yekutiza mumufananidzo wedu, haina kuratidzwa mune mamwe mapaneru.Onawo mufananidzo.S4.(D) Iko kushanduka kwekuchinja kunoitika musero tsika uye varwere vane hutachiona vanosvikirwa neiyo nucleotide imwe chete, uye kusungwa kwemasoja ekudzivirira ekudzivirira hakukonzeri chero mutengo wakakura kuACE2 affinity [sekuyerwa nembiriso yekuratidzira nzira (7)].Imwe neimwe pfungwa ndeyekuchinja, uye chimiro chayo uye ruvara zvinoratidza kana inogona kuwanikwa uye kusarudzwa panguva yekukura kwehutachiona.Mamwe mapoinzi ekurudyi pa x-axis anoratidza akasimba ekurwisa masoja ekudzivirira chirwere anosunga kutiza;iwo mapoinzi epamusoro pane y-axis anoratidza yakakwira ACE2 hukama.
Kuti tione kana Escape Atlas inogona kuongorora shanduko yehutachiona huchitapurira vanhu, takaongorora yakadzama yekuteedzera data kubva kune anoramba aine hutachiona immunocompromised murwere akagamuchira REGN-COV2 pazuva rechigumi nemakumi mana neshanu mushure mekuonekwa kweCCIDID-19 Kurapwa (16).Kunonoka kurapwa kunobvumira huwandu hwehutachiona hwemurwere huunganidze genetic siyana, mamwe acho anogona kufambiswa nekunetsekana kwemuviri, nekuti murwere ane asina kusimba autoneutralizing antibody mhinduro isati yarapwa (16).Mushure mekutonga kweREGN-COV2, kuwanda kwemaamino acid mashanu ekuchinja muRBD kwakachinja nekukurumidza (Mufananidzo 2C uye Mufananidzo S4).Mepu yedu yekutiza yakaratidza kuti matatu ekuchinja uku akatiza REGN10933 uye mumwe akatiza REGN10987 (Mufananidzo 2B).Izvo zvakakosha kucherechedza kuti mushure mekurapwa kweantibody, hazvisi zvese shanduko dzakaendeswa kunzvimbo yakatarwa.Pane zvinopesana, kune kukwira nekudonha kwemakwikwi (Mufananidzo 2C).Iyi muenzaniso yakaonekwa mukushanduka kwemukati kwekugadzirisa mauto emamwe mavhairasi (17, 18), zvichida nekuda kwekukwikwidzana pakati pemajini emahara-akasununguka uye mitsara yehutachiona.Ose masimba aya anoita seanoita basa muvarwere vane hutachiona hunoramba huchienderera mberi (Mufananidzo 2C uye Mufananidzo S4C): E484A (kwete shanduko yekupukunyuka mudhayagiramu yedu) uye F486I (kupukunyuka REGN10933) kusununguka-kutasva mushure mekurapwa, uye mitsara yehutachiona inotakura N440D Uye. Q493K (kupukunyuka REGN10987 uye REGN10933, zvichiteerana) yakatanga kukwikwidza neREGN10933 kutiza mutant Y489H, ndokuzokwikwidza nedzinza rakatakura E484A neF486I neQ493K.
Matatu paana mana ekuchinja ekutiza muvarwere vakarapwa neREGN-COV2 haana kuzivikanwa muRegeneron's virus cell tsika sarudzo (Mufananidzo 2B), inoratidza mukana wemepu yakazara.Kusarudzwa kwehutachiona hakuna kukwana nekuti vanogona kungoziva chero shanduko dzakasarudzwa zvisina tsarukano mune iyo chaiyo sero tsika kuyedza.Kusiyana neizvi, mepu yakazara inotsanangura shanduko dzese, dzinogona kusanganisira shanduko dzinokonzerwa nezvikonzero zvisingaenderane nekurapa, asi netsaona inokanganisa kusungirirwa kweantibody.
Ehe, kushanduka kwemavhairasi kunokanganiswa nekusagona kushanda uye kumanikidza kunzvenga masoja ekudzivirira chirwere.Iko kuchinja uye varwere vanosarudzwa musero tsika vanogara vachisangana neanotevera maitiro: ivo vanotiza antibody kusunga, vanogona kupinda nekamwe nucleotide shanduko, uye vane shoma kana kusabhadhara mutengo kuACE2 affinity [kuburikidza neyakapfuura yakadzika shanduko yakaratidzwa uchishandisa yeast Scanning kuyerwa RBD (7 )] (Mufananidzo 2D uye Mufananidzo S5).Naizvozvo, mepu yakazara yekuti shanduko dzinokanganisa sei kiyi biochemical phenotypes yeRBD (yakadai seACE uye antibody binding) inogona kushandiswa kuongorora nzira dzinogona kuitika dzehutachiona.Imwe caveat ndeyokuti munguva yakareba yekushanduka-shanduka, sezvinoonekwa muhutachiona hwehutachiona uye kupukunyuka kwezvinodhaka, nekuda kwekubatana kwepistatic, nzvimbo yekushivirira yekuchinja inogona kuchinja (19-21).
Mepu izere inotitendera kuti tiongorore aripo ekutiza shanduko mune inotenderera SARS-CoV-2.Isu takatarisa ese aripo-anotorwa nevanhu SARS-CoV-2 kutevedzana kubva muna Ndira 11, 2021 uye takaona kuti nhamba huru yeRBD shanduko yakapukunyuka imwe kana anopfuura masoja ekudzivirira chirwere (Mufananidzo 3).Zvakadaro, iyo chete yekutiza mutation iripo mu> 0.1% yekutevedzana ndeye REGN10933 kupukunyuka mutant Y453F [0.3% yekutevedzana;ona (12)], REGN10987 kutiza mutant N439K [1.7% yekutevedzana;ona Mufananidzo 1C uye (22)], Uye LY-CoV016 kutiza mutation K417N (0.1% kutevedzana; onawo Mufananidzo 1C).Y453F inobatanidzwa nekubuda kwakazvimirira kwakabatana nemapurazi emink muNetherlands neDenmark (23, 24);zvakakosha kucherechedza kuti mink sequence pachayo dzimwe nguva ine mamwe machinjiro ekupukunyuka, seF486L (24).N439K yakakurumbira muEurope, uye inoumba chikamu chikuru chekutevedzana kubva kuScotland neIreland muEurope (22, 25).K417N iripo mumutsara weB.1.351 yakatanga kuwanikwa muSouth Africa (10).Imwe shanduko yezvinonetsa ndeyeN501Y, iyo iripo muB.1.351 uye zvakare mumutsara weB.1.1.7 wakatanga kuzivikanwa muUK (9).Mepu yedu inoratidza kuti N501Y haina mhedzisiro paREGN-COV2 antibody, asi ine mwero maitiro paLY-CoV016 (Mufananidzo 3).
Kune yega yega antibody kana antibody musanganiswa, kubva muna Ndira 11, 2021, pakati pe317,866 yemhando yepamusoro-yakatorwa nevanhu SARS-CoV-2 sequences paGISAID (26), hukama pakati pekutiza mamakisi ega ega shanduko uye kuwanda kwayo.Yakanyorwa.Iyo REGN-COV2 cocktail yekupukunyuka mutation E406W inoda akawanda nucleotide shanduko muWuhan-Hu-1 RBD kutevedzana, uye haionekwe mukutevedzana kweGISAID.Mamwe machinjiro ezvakasara E406 (E406Q uye E406D) akaonekwa aine yakaderera frequency kuverenga, asi aya mutant amino acids haasi ega nucleotide mutations ari kure neW.
Sezvinotarisirwa, kutiza shanduko dzinowanzoitika mune anti-RBD interface.Nekudaro, chimiro chega hachina kukwana kufanotaura kuti ndedzipi shanduko dzinoyananisa kutiza.Semuenzaniso, LY-CoV016 inoshandisa cheni dzayo dzinorema uye dzakareruka kusunga kune yakafara epitope inodarika iyo ACE2 inosunga nzvimbo, asi maitiro ekupukunyuka anosanganisira shanduko mumasara eRBD mune inorema cheni kuwirirana kutsanangura dunhu (Mufananidzo 4A uye Mufananidzo S6, E kusvika. G).Mukupesana, kutiza kubva kuREGN10933 neREGN10987 zvakanyanya kuitika paRBD zvisaririra zvakarongedzerwa painterface yeanorema uye akareruka cheni (Mufananidzo 4A uye Mufananidzo S6, A kusvika D).Iyo E406W shanduko yakapukunyuka musanganiswa weREGN-COV2 yakaitika pazvisaririra zvanga zvisingabatane nechero antibody (Mufananidzo 4, A uye B).Kunyangwe E406 iri padhuze padyo neLY-CoV016 (Mufananidzo 4B uye Mufananidzo S6H), iyo E406W shanduko ine diki mhedzisiro pane antibody (Mufananidzo 1, B uye C), zvichiratidza kuti chaiyo-refu renji yekumisikidza inopesana neREGN. - COV2 antibody (Mufananidzo S6I).Muchidimbu, shanduko paRBD zvisaririra zvakasangana nemasoja ekudzivirira chirwere hazviwanzo kupindirana kutiza, uye kumwe kushanduka kwakakosha kwekupukunyuka kunoitika pazvisaririra zvisina kusangana nemasoja ekudzivirira chirwere (Figure 4B neFigure S6, D naG).
(A) Iyo dhizaini yekupukunyuka inoratidzwa pane iyo RBD chimiro chakasungwa neantibody.[REGN10933 uye REGN10987: Protein Database (PDB) ID 6XDG (11);LY-CoV016: PDB ID 7C01 (13)].Nzvimbo dzakasiyana-siyana dzemaketani anorema uye akareruka eantibody anoratidzwa semakatuni eblue, uye ruvara rwuri pamusoro peRBD runoratidza kusimba kwekupukunyuka-kwepakati-kwepakati panzvimbo ino (chena inoratidza kuti hapana kupukunyuka, uye tsvuku inoratidza yakasimba kwazvo. kutiza nzvimbo yemasoja ekudzivirira chirwere kana musanganiswa) .Masayiti asina kuchinjika akaitwa grey kunze.(B) Pamasoja emasoja ega ega, isai nzvimbo yacho seatomu asiri ehydrogen mukati me4Å yemasoja ekudzivirira chirwere), masoja ekudzivirira chirwere ari proximal (4 kusvika 8Å) kana distal antibody (> 8Å).Imwe neimwe poindi inomiririra saiti, yakakamurwa kutiza (tsvuku) kana isiri-kutiza (dema).Iyo grey dashed line inomiririra kukosha kwakakosha kunoshandiswa kurongedza saiti sekutiza kana kusapukunyuka (kuti uwane ruzivo, ona Zvishandiso uye Nzira).Nhamba dzvuku uye nhema dzinoratidza kuti ingani masaiti muchikamu chega chega akatiza kana kuti haana kupukunyuka.
Muchidzidzo ichi, takanyatso mepu shanduko dzinonzvenga matatu makuru e-anti-SARS-CoV-2 masoja ekudzivirira chirwere.Mamepu aya anoratidza kuti chimiro chekare chekupukunyuka shanduko hakuna kukwana.Hapana kana imwe amino acid shanduko inogona kutiza masoja ekudzivirira chirwere muREGN-COV2 cocktail yakaonekwa, uye havana kuona ruzhinji rwevarwere vanoramba vachibatwa nechirwere ichi.mutation.Ehe, mepu yedu haisati yapindura mubvunzo unonyanya kudzvanya: Ko SARS-CoV-2 ichakura kuramba masoja ekudzivirira chirwere aya?Asi chii chiri chokwadi ndechekuti zviri kunetsa kuti machinjiro mazhinji anotiza ane zvishoma paRBD kupeta kana receptor affinity, uye kwatove nekuchinja kwakadzika-chikamu mukutenderera kwehutachiona.Mukupedzisira, zvinodikanwa kumirira uye kuona izvo shanduko iyo SARS-CoV-2 ichaendesa kana yapararira pakati pehuwandu.Basa redu richabatsira "kutarisa" nekukasira kutsanangura kukanganisa kwekuchinja kwakaiswa nehutachiona genome surveillance.
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Tyler N.Starr, Allison J.Greaney, Amin Addetia, William W. Hannon, Manish C. Choudhary (Manish C. Choudhary), Adam S. Dinges (Adam S.
Mepu yakazara yeSARS-CoV-2 shanduko inopukunyuka Regeneron monoclonal antibody musanganiswa inobatsira kutsanangura shanduko yehutachiona mukurapa varwere.
Tyler N.Starr, Allison J.Greaney, Amin Addetia, William W. Hannon, Manish C. Choudhary (Manish C. Choudhary), Adam S. Dinges (Adam S.
Mepu yakazara yeSARS-CoV-2 shanduko inopukunyuka Regeneron monoclonal antibody musanganiswa inobatsira kutsanangura shanduko yehutachiona mukurapa varwere.
©2021 American Association for the Advancement of Science.kodzero dzose dzakachengetedzwa.AAAS ishamwari yeHINARI, AGORA, OARE, CHORUS, CLOCKSS, CrossRef uye COUNTER.Science ISSN 1095-9203.
Nguva yekutumira: Feb-24-2021