Potent SARS-CoV-2 neutralizing antibodies with therapeutic effects in two animal models

Potent neutralizing broad-spectrum antibody against SARS-CoV-2 generated from dual-antigen-specific B cells from convalescents

“…We had previously generated approximately 500 antibodies using only the RBD of the Wuhan strain; however, few of them were broadly effective. 16 In contrast, multiple antibodies that were effective against the Delta and some of the Omicron variant were obtained in this study, even though we only used the RBD of Wuhan strain and the Gamma variant when selecting B cells, and only samples from SARS-CoV-2-infected patients before the appearance of the Alpha variant were used. This is presumably because E484, K417, and N501, which is known as mutations in the RBD of the Gamma variant, were major targets of human humoral immunity to SARS-CoV-2.…”

“…We examined the effect of the mutation on the selected antibodies. For comparison, we examined antibodies that we had previously produced from convalescent peripheral B cells selected using Wuhan-RBD alone 16 and therapeutic antibodies. 17 In addition to the previous five strains, we also examined the spike from four others, the Delta4+ variant described previously, 18 the Mu variant, the Omicron variant (BA.1), and SARS-CoV-1.…”

“…We previously generated antibodies from B cells collected from convalescent patients that could bind the RBD of Wuhan-hu-1 as bait; however, most of the antibodies recognized the area around E484, which is considered to be a major epitope of RBD, and few antibodies were effective against the Beta, Gamma, and Omicron variants. 16 Here, by using two types of RBDs, the Wuhan strain and the Gamma variant as bait, we successfully generated antibodies that are broadly effective against multiple variants, even including the Delta and some of the Omicron variants.…”

Overcoming antibody-resistant SARS-CoV-2 variants with bispecific antibodies constructed using non-neutralizing antibodies

“…Consequently, the clinical application of anti-RBD antibodies has led to reduced neutralization and inhibitory activities. 22,27,30,31,57 Although efforts to develop broadly neutralizing antibodies that target pan-coronavirus conserved epitopes are actively underway, [58][59][60][61][62][63][64][65] the possibility of emerging immune-evading mutant variants remains, posing a recurrent challenge to monoclonal antibody therapy. Therefore, the exploration of alternative approaches is attractive.…”

Novel Omicron Variants Enhance Anchored Recognition of TMEM106B: A New Pathway for SARS-CoV-2 Cellular Invasion

“…Based on this post-relaxation structure, two parallel 500 ns MD simulations were performed for each of the three complexes of the WT (TMEM106B–WT) and variants (TMEM106B–BA.2.86/EG.5.1) to obtain equilibrium trajectories for subsequent energy and confirmation analysis. The molecular mechanics/generalized Born surface area (MM/GBSA) method was employed to assess the binding affinity and the individual energy terms of the three complexes, , while the alanine scanning (AS) mutagenesis method was utilized to identify the effect of mutations on the affinity contribution of binding interface residues. , In addition, we further dissected the structure–dynamics characterization of WT/BA.2.86/EG.5.1 RBDs with TMEM106B through umbrella sampling (US), and we provide a reliable reference for antibody design by analyzing the residues at the binding interface for six representative antibodies. − We aspire that this study will provide a novel perspective for the prevention and treatment of this new viral invasion pathway.…”