The receptor-binding domain name (RBD) located in the S1 region is responsible for directly binding to the host cell receptor, angiotensin-converting enzyme 2 (ACE2). 57.8 million people and cause more than 1300000 deaths in nearly all countries by November 22, 2020 (World Health Organization, 2020). Thus, there is a great demand for effective therapies for the prevention and treatment of COVID-19. Therapeutic neutralizing antibodies (NAbs), which could block viral infection, may be such a promising approach, as NAbs have been successfully applied to the treatment of respiratory syncytial computer virus infection and showed great potential for the treatment of other viral infections (Walker and Burton, 2018). The advances of antibody technology have greatly accelerated the discovery of SARS-CoV-2 NAbs, and many of which are now actively tested in clinical trials (by the time this review is usually finalizing, Regenerons antibody cocktail therapy has received Emergency Use Authorization from the US Food and Drug Administration). Here, we review the approaches applied for SARS-CoV-2 NAb development and discuss the emerging technologies underlining the antibody discovery. We further summarize the common features of these antibodies including the shared recognition epitopes and sequence features. Antibody diversification and antibody discovery A typical natural antibody composes of two identical heavy chains and two identical light chains, which is usually coded by immunoglobulin (gene loci (Alt et?al., 2013). During the development of B cell, V(D)J recombination assembles the numerous V, D, and J gene segments into a variable region exon, forming the first step of antibody diversification. Upon antigen stimulation, B cells undergo another round of diversification by somatic hypermutation (SHM), whereby mutations and small insertions and deletions (indels) are introduced into the variable region exon (Yeap and Meng, 2019). B cells with mutations that increase binding affinity to the antigen are selected in a process called affinity maturation (Alt et?al., 2013). Thus, the diversity in an antibody repertoire, contributed by V(D)J recombination and/or SHM processes from previous immune responses, ensures an effective antibody-mediated immunity upon exposure to a novel pathogen. The inventions of A-1165442 hybridoma technology (Kohler and Milstein, 1975), humanized antibody (Kinashi et?al., 1986), and phage surface display (Smith, 1985) have made antibody the most widely used protein reagents in both biomedical Amotl1 research and therapy. In the past few years, emerging new technologies have again boosted the antibody discovery process, including paired antibody gene cloning from single B cells (Tiller et?al., 2008), improved memory B-cell sorting and culturing (Huang et?al., 2013; Corti and Lanzavecchia, 2014), single-cell RNA Sequencing (Tang et?al., 2009), antibody-humanized mouse models (originally proposed by Alt et?al., 1985), and the discovery of single-domain antibody (Hamers-Casterman et?al., 1993). Approaches to develop SARS-CoV-2 NAbs Within a few months after the pandemic begins, A-1165442 many research groups have successfully isolated SARS-CoV-2 NAbs from COVID-19 convalescent patients (Rogers et?al., 2020; Seydoux et?al., 2020; Shi et?al., 2020; Wu et?al., 2020b). A commonality in the approaches used by these groups includes the enrichment of specific B cells using SARS-CoV-2 spike A-1165442 (S) protein, since antibodies targeting the spike may block entry of the computer virus into the host cell. The SARS-CoV-2 S protein that forms a trimeric complex at the computer virus membrane is divided into two regions, the S1 region that mediates computer virus attachment to the host cell and the S2 region that triggers computer virus fusion (Wrapp et?al., 2020b). The receptor-binding domain name (RBD) located in the S1 region is responsible for directly binding to the host cell receptor, angiotensin-converting enzyme 2 (ACE2). In this context, both S1 and S-RBD A-1165442 fragments were used to label the human B cells in fluorescence-activated cell sorting-based single-cell sorting. Several potent NAbs that were discovered using such approaches include B38 (Wu et?al., 2020b), CB6 (Shi et?al., 2020), CC12.1 (Rogers et?al., 2020), C121 (Robbiani et?al., 2020), and CV30 (Seydoux et?al., 2020). To search for antibodies that have broader neutralizing activities against several coronavirus strains, peripheral blood mononuclear cells (PBMCs) from SARS-CoV convalescent patients were used and the resulting antibodies, e.g. ADI-55689, can neutralize both SARS-CoV-2 and SARS-CoV (Pinto et?al., 2020; Wec et?al., 2020). Along the same line, Epstein-Barr computer virus transformation-based single B-cell culture (Traggiai et?al., 2004) also yielded a cross-reactive A-1165442 NAb, S309, from SARS-CoV convalescent patients (Pinto et?al., 2020). High-throughput single-cell 5?RNA-Seq further facilitates the antibody discovery. In this context, 10 Genomics technology was applied to identify paired heavy and light chain V(D)J sequences from tens of thousands of single B cells. Two impartial groups have applied bioinformatic pipelines.