On Sep. 3rd, 2021, the Su lab from Biomedical Pioneering Innovation Center (BIOPIC), School of Life Sciences in Peking University, collaborating with Youchun Wang from the National Institutes for Food and Drug Control, published a paper entitled “Structure-based Analyses of Neutralization Antibodies Interacting with Naturally Occurring SARS-CoV-2 RBD Variants” in Cell Research, investigating the impacts of multiple SARS-CoV-2 naturally occurring variants on potent NAbs.

　　Neutralizing antibodies (NAbs) are critical for effective therapy of COVID-19 caused by infection of SARS-CoV-2. SARS-CoV-2 enters host cells through the interaction of Spike protein with the receptor ACE2 anchored on the membrane of host cells. However, the variant lineages of SARS-CoV-2 aroused wide concern for their possibility of escaping from the neutralization of many previously antibodies and partly reducing the neutralization generated by vaccination or previous infection.

　　Most published human NAbs have been isolated from convalescing patients, and the effective ones target mainly to the RBD of trimeric S protein. Among the potent NAbs, many showed significant therapeutic and prophylactic efficacy. For example, BD-368-2, could bind to both “up” and “down” RBDs. Furthermore, the VH3-53/3-66 class-derived “public antibodies” were the most widespread NAb class, and was identified in many infected patients worldwide1-4.

　　The binding affinities of potent NAbs to SARS-CoV-2 RBD variants were investigate by surface plasmon resonance (SPR). The results showed that the VH3-53/3-66 class of NAbs performed high affinity in interacting with most of the variants, with their KDs from nanomoles to picomoles. Structures of different RBD variants in complex with BD-503, one of the VH3-53 germline-based antibody, was determined and explained the reduced interaction affinities of the germline-based antibodies to RBD-E484K, RBD-N501Y and RBD-501Y.V2 (Fig.1).

　　Figure 1. Impacts of SARS-CoV-2 RBD variants interacting with potent NAbs

　　Youchun Wang’s lab performed pseudovirus neutralization assays to confirm that these germline-based antibodies kept high neutralizing/protecting efficacy against most S protein variants with EC50 < μg/mL except BD-508 and BD-623 showed lower neutralizing efficacy to a few variants (Fig.2).

　　Besides, another two antibodies were also investigated and the BD-368-2, previously shown to have the best therapeutic and prophylactic efficacies against SARS-CoV-2, completely lost neutralizing activity to variants containing E484K mutation, while the BD-218 performed well and even had higher EC50s to most of the variants except F486L and Y489H mutations.

　　Figure 2. Neutralizing abilities of NAbs.

　　The results sowed that the BD-515, BD-604 and BD-218 can still be preferred candidates against COVID-19.

　　Ph.D. candidate Hua Xu, Bo Wang, Tianning Zhao and Ziteng Liang are the co-first authors of the paper. Prof. Xiaodong Su and Prof. Youchun Wang are the co-corresponding authors of the paper. This project was supported by the Ministry of Science and Technology of China and the Qidong-SLS Innovation Fund to X.D.S. This project was also supported by the Beijing Science and Technology Project, the National Natural Science Foundation of China, and the National Key Research and Development Program of China to Youchun Wang.