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SARS-CoV-2 proteins

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    Cross-neutralization antibodies against SARS-CoV-2 and RBD mutations from convalescent patient antibody libraries

    Authors: Yan Lou; Wenxiang Zhao; Haitao Wei; Min Chu; Ruihua Chao; Hangping Yao; Junwei Su; Yanan Li; Xiulan Li; Yu Cao; Yanyan Feng; Ping Wang; Yongyang Xia; Yushuan Shang; Fengping Li; Pingju Ge; Xinglin Zhang; Wenjing Gao; Bing Du; Tingbo Liang; Yunqing Qiu; Minyao Liu

    doi:10.1101/2020.06.06.137513 Date: 2020-06-06 Source: bioRxiv

    The emergence of coronavirus disease 2019 MESHD ( COVID-19 MESHD) pandemic led to an urgent need to develop therapeutic interventions. Among them, neutralizing antibodies play crucial roles for preventing viral infections MESHD and contribute to resolution of infection. Here, we describe the generation of antibody libraries from 17 different COVID-19 MESHD recovered patients and screening of neutralizing antibodies to SARS-CoV-2. After 3 rounds of panning, 456 positive phage clones were obtained with high affinity to RBD (receptor binding domain). Then the positive clones were sequenced and reconstituted into whole human IgG for epitope binning assays. After that, all 19 IgG were classified into 6 different epitope groups or Bins. Although all these antibodies were shown to have ability to bind RBD, the antibodies in Bin2 HGNC have more superiority to inhibit the interaction between spike protein PROTEIN and angiotensin converting enzyme 2 receptor ( ACE2 HGNC). Most importantly, the antibodies from Bin2 HGNC can also strongly bind with mutant RBDs (W463R, R408I, N354D, V367F and N354D/D364Y) derived from SARS-CoV-2 strain with increased infectivity, suggesting the great potential of these antibodies in preventing infection of SARS-CoV-2 MESHD and its mutations. Furthermore, these neutralizing antibodies strongly restrict the binding of RBD to hACE2 HGNC overexpressed 293T cells. Consistently, these antibodies effectively neutralized pseudovirus entry into hACE2 HGNC overexpressed 293T cells. In Vero-E6 cells, these antibodies can even block the entry of live SARS-CoV-2 into cells at only 12.5 nM. These results suggest that these neutralizing human antibodies from the patient-derived antibody libraries have the potential to become therapeutic agents against SARS-CoV-2 and its mutants in this global pandemic.

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MeSH Disease
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SARS-CoV-2 Proteins


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