Cov kab mob tshiab ntawm SARS-CoV-2 (tus kab mob ua lub luag haujlwm rau COVID-19): Puas yog 'Neutralising Antibodies' Txoj Kev Ua Tau Teb rau Kev Hloov Tawm sai sai?

Ntau yam tshiab ntawm cov tus kab mob no tau tshwm sim txij li tus kabmob kis tau pib. Cov kev hloov pauv tshiab tau tshaj tawm thaum ntxov Lub Ob Hlis 2020. Qhov hloov pauv tam sim no uas tau coj Tebchaws Askiv kom sawv ntsug rau Christmas no tau hais tias muaj 70% kis ntau dua. Raws li kev pom ntawm cov kab mob tshwm sim, puas yuav muaj ntau yam tshuaj tiv thaiv uas tau tsim thoob ntiaj teb tseem muaj txiaj ntsig txaus rau cov kev hloov pauv tshiab thiab? 'Neutralising Antibody' mus kom ze rau lub hom phiaj tus kab mob no zoo li muaj kev cia siab rau hauv qhov kev nyab xeeb tam sim no ntawm kev tsis paub tseeb. Qhov xwm txheej yog tias yim qhov tshuaj tiv thaiv kab mob tsis zoo tiv thaiv SARS-CoV-2 tam sim no tab tom sim tshuaj xyuas, suav nrog kev sim ntawm 'antibody cocktails' txhawm rau kov yeej qhov muaj peev xwm ntawm tus kab mob no txhim kho tsis kam mus rau ib qho tshuaj tiv thaiv ib leeg los ntawm kev sib sau ua ke ntawm kev hloov pauv.

cov SARS-Cov-2 tus kab mob no lub luag haujlwm rau Covid-19 Kab mob kis thoob qhov txhia chaw yog tus kab mob betacoronavirus hauv tsev neeg coronaviridae kab mob. Qhov no tus kab mob no muaj qhov zoo-sensitive RNA genome, txhais tau hais tias ib leeg strand RNA ua raws li tus tub txib RNA thaum txhais ncaj qha rau hauv cov kab mob sib kis hauv tus tswv tsev. Lub genome ntawm SARS-CoV-2 encodes plaub yam qauv proteins {spike (S), hnab ntawv (E), daim nyias nyias (M), thiab nucleocapsid (N)} thiab 16 non-structural proteins. Thaum cov txheej txheem cov proteins ua lub luag haujlwm hauv kev lees paub ntawm tus tswv tsev cell, membrane fusion, thiab cov kab mob nkag mus tom ntej; Cov proteins uas tsis yog qauv (NSPs) ua lub luag haujlwm tseem ceeb hauv kev ua haujlwm xws li RNA polymerization los ntawm RNA-dependent RNA polymerase (RdRp, NSP12). 

Qhov tseem ceeb, RNA tus kab mob no polymerases tsis muaj proofreading nuclease kev ua, txhais tau hais tias tsis muaj lub tshuab muaj los xyuas qhov yuam kev thaum transcription lossis replication. Yog li ntawd, kab mob ntawm tsev neeg no qhia tau tias muaj kev hloov pauv lossis hloov pauv ntau heev. Qhov no ua rau lawv cov kev hloov pauv ntawm genome thiab evolution yog li muab lawv qib siab ntawm kev hloov pauv thiab pab cov tus kab mob no khiav tawm ntawm kev tiv thaiv ntawm tus tswv tsev thiab tsim kev tiv thaiv tiv thaiv cov tshuaj tiv thaiv ^(1,2,3). Pom tseeb, nws ib txwm yog qhov xwm txheej ntawm RNA kab mob, suav nrog tus mob coronaviruses kom dhau mus hloov pauv hauv lawv cov genome ntawm tus nqi siab heev txhua lub sijhawm vim yog vim li cas tau hais los saum no. Cov replication yuam kev uas pab cov tus kab mob no kov yeej tsis zoo xaiv siab, ua rau adaptation ntawm lub tus kab mob no. Nyob rau hauv lub sij hawm ntev, ntau qhov kev ua yuam kev, ntau qhov kev hloov kho. Tseem, Covid-19 yog thawj daim ntawv sau txog tus mob coronavirus pandemic hauv keeb kwm. Nws yog daim ntawv thib tsib uas muaj kev sib kis thoob plaws txij li xyoo 1918 tus mob khaub thuas Spanish; tag nrho ntawm plaub qhov kev mob kis thoob qhov txhia chaw tau tshwm sim los ntawm tus mob khaub thuas kab mob ⁽⁴⁾.  

Pom tau tias, tib neeg tus kabmob coronaviruses tau tsim kev hloov pauv thiab hloov pauv hauv 50 xyoo dhau los. Muaj ntau qhov kev sib kis txij li xyoo 1966, thaum thawj qhov kev sib kis tau raug kaw. Thawj tus neeg tuag mob hlwb Kev sib kis tau tshwm sim xyoo 2002 hauv xeev Guangdong, Tuam Tshoj uas yog tshwm sim los ntawm tus kab mob variant SARS-CoV ua raws li xyoo 2012 kev kis mob hauv Saudi Arabia los ntawm qhov txawv ntawm MERS-CoV. Qhov xwm txheej tam sim no tshwm sim vim SARS-CoV-2 qhov txawv txav tau pib thaum Lub Kaum Ob Hlis 2019 hauv Wuhan, Tuam Tshoj, thiab tom qab ntawd kis thoob ntiaj teb dhau los ua thawj tus kabmob kis kabmob kis mus rau Covid-19 kab mob. Tam sim no, muaj ob peb sub-variants kis thoob plaws lub teb chaws sib txawv. SARS-CoV-2 kuj tau qhia txog kev sib kis ntawm tib neeg thiab tsiaj txhu thiab rov qab mus rau tib neeg⁽⁵⁾.

Kev tsim tshuaj tiv thaiv tiv thaiv tib neeg mob hlwb tau pib tom qab xyoo 2002 muaj kev sib kis. Ntau cov tshuaj tiv thaiv kab mob SARS-CoV thiab MERS-CoV tau tsim thiab raug sim ua ntej tab sis ob peb tus neeg tau sim. Tsis muaj leej twg tau txais kev pom zoo los ntawm FDA tab sis ⁽⁶⁾. Cov kev siv zog no tau los ua ke hauv kev tsim tshuaj tiv thaiv tiv thaiv SARS-CoV-2 los ntawm kev siv cov ntaub ntawv kho mob uas twb muaj lawm nrog rau cov uas cuam tshuam txog kev tsim tshuaj tiv thaiv tau ua thaum tsim cov tshuaj tiv thaiv rau SARS-CoV thiab MERS-CoV. ⁽⁷⁾. Lub sijhawm no, muaj ntau yam tshuaj tiv thaiv SARS-CoV-2 nyob rau theem siab heev; ob peb twb tau txais kev pom zoo ua EUA (Kev Tso Cai Siv Kub Kub). Kwv yees li ib nrab lab tus neeg muaj kev pheej hmoo siab hauv UK twb tau txais Pfizer's mRNA tshuaj tiv thaiv. Thiab, ntawm no los ntawm tsab ntawv ceeb toom ntawm qhov tshwm sim tshiab, kis tau zoo heev (lossis, kab mob sib kis) ntawm SARS-CoV-2 hauv UK lub sijhawm Christmas no. Ib ntus hu ua VUI-202012/01 lossis B117, qhov sib txawv no muaj 17 kev hloov pauv nrog rau ib qho ntawm cov protein ntau. Ntau kis tsis tas txhais tau tias tus tus kab mob no tau ua txaus ntshai rau tib neeg. Lawm, ib qho xav tsis thoob yog tias cov tshuaj tiv thaiv no tseem yuav muaj txiaj ntsig txaus rau cov hloov pauv tshiab thiab. Nws tau sib cav hais tias ib qho kev hloov pauv ntawm tus kab mob yuav tsum tsis txhob ua cov tshuaj tiv thaiv ('thaj tsam thaj tsam' lub hom phiaj) cov tshuaj tiv thaiv tsis zoo tab sis raws li kev hloov pauv ntau dhau sijhawm, cov tshuaj tiv thaiv yuav xav tau kev kho kom zoo kom haum rau cov tshuaj tiv thaiv kab mob. ^(8,9)

Antibody mus kom ze: rov hais dua qhov tseem ceeb ntawm neutralizing antibodies tej zaum yuav yog qhov tseem ceeb 

Nws yog nyob rau hauv keeb kwm yav dhau los uas 'antibody mus kom ze' (suav nrog 'neutralizing antibodies tiv thaiv SARS-Cov-2 tus kab mob no' thiab 'cov tshuaj tiv thaiv kab mob tiv thaiv Covid-19-associated hyperinflamation') nce qhov tseem ceeb. Neutralizing antibodies tiv thaiv SARS-CoV-2 tus kab mob no thiab nws cov kev hloov pauv tuaj yeem ua rau 'npaj siv' cov cuab yeej tiv thaiv kab mob.  

cov neutralizing cov tshuaj tiv thaiv phiaj lub kab mob ncaj qha rau hauv tus tswv tsev thiab tuaj yeem muab kev tiv thaiv sai tshwj xeeb tshaj yog tawm tsam txhua qhov kev hloov tshiab tshiab. Txoj kev no tseem tsis tau pom muaj kev vam meej ntau tab sis muaj peev xwm los daws qhov teeb meem ntawm antigenic drift thiab muaj peev xwm txhaj tshuaj tiv thaiv tsis sib haum uas tau nthuav tawm los ntawm kev hloov pauv sai thiab hloov pauv SARS-CoV-2. tus kab mob no. Raws li nyob rau 28 Lub Xya Hli 2020, yim neutralizing antibodies tiv thaiv SARS-CoV-2 tus kab mob no (namely LY-CoV555, JS016, REGN-COV2, TY027, BRII-196, BRII-198, CT-P59, and SCTA01) tau raug soj ntsuam soj ntsuam. Ntawm no neutralizing antibodies, LY-CoV555 yog Monoclonal Antibody (mAb). VIR-7831, LY-CoV016, BGB-DXP593, REGN-COV2, thiab CT-P59 yog lwm cov tshuaj tiv thaiv kab mob monoclonal raug sim ua cov tshuaj tiv thaiv tsis zoo. Antibody cocktails tuaj yeem kov yeej txhua qhov kev tawm tsam tsim tawm los tiv thaiv ib qho tshuaj tiv thaiv ib leeg, yog li cov cocktails xws li REGN-COV2, AZD7442, thiab COVI-SHIELD kuj tseem tab tom mus kuaj mob. Txawm li cas los xij, hom kab mob yuav maj mam txhim kho kev tiv thaiv rau cocktails thiab. Tsis tas li ntawd, tej zaum yuav muaj kev pheej hmoo ntawm kev tiv thaiv kab mob tiv thaiv kab mob (ADE) vim yog tshuaj tiv thaiv uas tsuas khi rau lub tus kab mob no thiab tsis muaj peev xwm ntawm neutralizing lawv, yog li ua rau cov kab mob zuj zus ntxiv ^(10,11). Yuav tsum muaj kev tshawb fawb txuas ntxiv mus ntxiv los daws cov teeb meem no. 

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Tshooj cai: COVID-19: 'Neutralising Antibody' Kev sim pib hauv UK

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References: 

1. Elena S thiab Sanjuán R., 2005. Adaptive Value of High Mutation Rates of RNA kab mob: Sib cais ua rau muaj tshwm sim. ASM Journal of Virology. DOI: https://doi.org/10.1128/JVI.79.18.11555-11558.2005   

2. Bębenek A., thiab Ziuzia-Graczyk I., 2018. Fidelity of DNA replication—ib qho teeb meem ntawm kev nyeem ntawv. Tam sim no Genetics. 2018; 64(5): 985–996. DOI: https://doi.org/10.1007/s00294-018-0820-1  

3. Pachetti M., Marini B., et al., 2020. Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant. Phau ntawv Journal of Translational Medicine volume 18, Tshooj xov tooj: 179 (2020). Published: 22 Plaub Hlis 2020. DOI: https://doi.org/10.1186/s12967-020-02344-6 

4. Liu Y., Kuo R., thiab Shih H., 2020. COVID-19: Thawj cov ntaub ntawv sau txog tus kabmob coronavirus hauv keeb kwm. Biomedical Journal. Nqe 43, Nqe 4, Lub Yim Hli 2020, Nplooj 328-333. DOI: https://doi.org/10.1016/j.bj.2020.04.007  

5. Munnink B., Sikkema R., et al., 2020. Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans. Science 10 Nov 2020: ebe5901. DOI: https://doi.org/10.1126/science.abe5901  

6. Li Y., Chi W., et al., 2020. Kev tsim tshuaj tiv thaiv kab mob Coronavirus: los ntawm SARS thiab MERS mus rau COVID-19. Phau ntawv Journal of Biomedical Science ntim 27, Tshooj xov tooj: 104 (2020). Published: 20 December 2020. DOI: https://doi.org/10.1186/s12929-020-00695-2  

7. Krammer F., 2020. SARS-CoV-2 vaccines in development. Xwm Txheej 586, phab 516–527(2020). Published: 23 September 2020. DOI: https://doi.org/10.1038/s41586-020-2798-3  

8. Koyama T., Weeraratne D., et al., 2020. Kev tshwm sim ntawm Drift Variants Tej zaum yuav cuam tshuam rau COVID-19 Kev Txhaj Tshuaj Tiv Thaiv thiab Kev Kho Mob Antibody. Cov kab mob 2020, 9(5), 324; DOI: https://doi.org/10.3390/pathogens9050324  

9. BMJ 2020. Xov Xwm Tshaj Tawm. Covid-19: Tus kab mob coronavirus tshiab tau txheeb pom hauv UK. Luam tawm 16 Kaum Ob Hlis 2020. DOI: https://doi.org/10.1136/bmj.m4857  

10. Renn A., Fu Y., et al., 2020. Fruitful Neutralizing Antibody Pipeline Brings Hope To Defeat SARS-Cov-2. Trends nyob rau hauv Pharmacological Sciences. Nqe 41, Nqe 11, Kaum Ib Hlis 2020, Nplooj 815-829. DOI: https://doi.org/10.1016/j.tips.2020.07.004  

11. Tuccori M., Ferraro S., et al., 2020. Anti-SARS-CoV-2 neutralizing monoclonal antibodies: clinical pipeline. mAbs Volume 12, 2020 - Issue 1. Published online: 15 Dec 2020. DOI: https://doi.org/10.1080/19420862.2020.1854149 

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