关键词： γ , Gamma δ , Delta ACE2, Angiotensin-converting enzyme 2 ADCC, Antibody-dependent cell-mediated cytotoxicity ADCP, Antibody-dependent cellular phagocytosis ADE, Antibody-dependent enhancement Alb, Albumin Bat-SL-CoV, Bat SARS-like coronavirus Broad neutralization CDC, Complement-dependent cytotoxicity CDR, Complementarity-determining region CH, Constant domain of antibody heavy chain CHO, Chinese hamster ovary CL, Constant domain of antibody light chain CNAR, Constant domain of immunoglobulin new antigen receptor COVID-19 COVID-19, Coronavirus disease 2019 Cryo-EM, Cryogenic electron microscopy Cu, Copper DNA, Deoxyribonucleic acid DPP4, Dipeptidyl peptidase 4 E, Envelope EC50, Half-maximal effective concentration FDA, The United States Food and Drug Administration Fab, Antigen-binding fragment Fc, Crystallisable fragment FcR, Crystallisable fragment receptor Fig., Figure HCoV, Human coronavirus HIV, Human immunodeficiency virus HR, Heptad repeat HRP, Horseradish peroxidase HV, Hypervariable region IC50, Half-maximal inhibitory concentration Ig, Immunoglobulin IgNAR, Immunoglobulin new antigen receptor KD, Equilibrium dissociation constant L, Litre LRT, Lower respiratory tract M, Membrane MERS, Middle East respiratory syndrome MERS-CoV, Middle East respiratory syndrome coronavirus N, Nucleocapsid ND50, 50% neutralizing dose NTD, N-terminal domain Nb, Nanobody PCR, Polymerase chain reaction PEG, Polyethylene glycol RBD, Receptor-binding domain RBM, Receptor-binding motif RNA, Ribonucleic acid S, Spike SARS, Severe acute respiratory syndrome SARS-CoV, Severe acute respiratory syndrome coronavirus SARS-CoV-2 mutation SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2 SPAAC, Strain-promoted azide-alkyne cycloaddition Single-domain antibody Spike protein TMPRSS2, Transmembrane serine protease 2 Therapeutic URT, Upper respiratory tract VH, Variable domain of antibody heavy chain VHH, Variable domain of camelid heavy-chain only antibody VL, Variable domain of antibody light chain VNAR, Variable domain of immunoglobulin new antigen receptor WHO, World Health Organization cDNA, Complementary deoxyribonucleic acid dpi, Days' post infection g, Gram kDa, Kilodalton koff, Dissociation rate constant mAb, Monoclonal antibody mRNA, Messenger ribonucleic acid nM, Nanomolar pM, Picomolar scFv, Single-chain variable fragment sdAb, Single-domain antibody ß, Beta α, Alpha

来  源：   DOI：10.1016/j.bea.2022.100054   PDF(Pubmed)

Abstract：
With severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an emergent human virus since December 2019, the world population is susceptible to coronavirus disease 2019 (COVID-19). SARS-CoV-2 has higher transmissibility than the previous coronaviruses, associated by the ribonucleic acid (RNA) virus nature with high mutation rate, caused SARS-CoV-2 variants to arise while circulating worldwide. Neutralizing antibodies are identified as immediate and direct-acting therapeutic against COVID-19. Single-domain antibodies (sdAbs), as small biomolecules with non-complex structure and intrinsic stability, can acquire antigen-binding capabilities comparable to conventional antibodies, which serve as an attractive neutralizing solution. SARS-CoV-2 spike protein attaches to human angiotensin-converting enzyme 2 (ACE2) receptor on lung epithelial cells to initiate viral infection, serves as potential therapeutic target. sdAbs have shown broad neutralization towards SARS-CoV-2 with various mutations, effectively stop and prevent infection while efficiently block mutational escape. In addition, sdAbs can be developed into multivalent antibodies or inhaled biotherapeutics against COVID-19.
摘要：
自2019年12月以来，严重急性呼吸道综合症冠状病毒2（SARS-CoV-2）已成为一种新兴的人类病毒，世界人口易患2019年冠状病毒病（COVID-19）。SARS-CoV-2比以前的冠状病毒具有更高的传播能力，由核糖核酸（RNA）病毒性质相关的高突变率，导致SARS-CoV-2变体在全球传播时出现。中和抗体被鉴定为针对COVID-19的即时和直接作用治疗剂。单结构域抗体（sdAb），作为具有非复杂结构和内在稳定性的小生物分子，可以获得与常规抗体相当的抗原结合能力，作为一种有吸引力的中和溶液。SARS-CoV-2刺突蛋白附着于肺上皮细胞上的人血管紧张素转换酶2（ACE2）受体以引发病毒感染，作为潜在的治疗靶点。sdAb已经显示出广泛的中和对SARS-CoV-2的各种突变，有效阻止和预防感染，同时有效阻止突变逃逸。此外,sdAb可以发展成为针对COVID-19的多价抗体或吸入性生物治疗剂。
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