Jisun Lee, Bomi Kim, Hye-Min Woo, Jun-Won Kim, Inji Jung, Seong-Wook Park, Yong-Sung Kim, Jung-Hyun Na, Sang Taek Jung
{"title":"Enhanced Omicron Variant Neutralization by a Human Antibody Tailored to Wild-Type and Delta-Variant SARS-CoV-2 RBDs.","authors":"Jisun Lee, Bomi Kim, Hye-Min Woo, Jun-Won Kim, Inji Jung, Seong-Wook Park, Yong-Sung Kim, Jung-Hyun Na, Sang Taek Jung","doi":"10.1021/acs.molpharmaceut.4c00297","DOIUrl":null,"url":null,"abstract":"<p><p>Given the previous SARS-CoV-2 pandemic and the inherent unpredictability of viral antigenic drift and shift, preemptive development of diverse neutralizing antibodies targeting a broad spectrum of epitopes is essential to ensure immediate therapeutic and prophylactic interventions during emerging outbreaks. In this study, we present a monoclonal antibody engineered for cross-reactivity to both wild-type and Delta RBDs, which, surprisingly, demonstrates enhanced neutralizing activity against the Omicron variant despite a significant number of mutations. Using an <i>Escherichia coli</i> inner membrane display of a human naïve antibody library, we identified antibodies specific to the wild-type SARS-CoV-2 receptor binding domain (RBD). Subsequent directed evolution via yeast surface display yielded JS18.1, an antibody with high binding affinity for both the Delta and Kappa RBDs, as well as enhanced binding to other RBDs (wild-type, Alpha, Beta, Gamma, Kappa, and Mu). Notably, JS18.1 (engineered for wild-type and Delta RBDs) exhibits enhanced neutralizing capability against the Omicron variant and binds to RBDs noncompetitively with ACE2, distinguishing it from other previously reported antibodies. This underscores the potential of pre-existing antibodies to neutralize emerging SARS-CoV-2 strains and offers insights into strategies to combat emerging viruses.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"4336-4346"},"PeriodicalIF":4.5000,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Pharmaceutics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1021/acs.molpharmaceut.4c00297","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/26 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Given the previous SARS-CoV-2 pandemic and the inherent unpredictability of viral antigenic drift and shift, preemptive development of diverse neutralizing antibodies targeting a broad spectrum of epitopes is essential to ensure immediate therapeutic and prophylactic interventions during emerging outbreaks. In this study, we present a monoclonal antibody engineered for cross-reactivity to both wild-type and Delta RBDs, which, surprisingly, demonstrates enhanced neutralizing activity against the Omicron variant despite a significant number of mutations. Using an Escherichia coli inner membrane display of a human naïve antibody library, we identified antibodies specific to the wild-type SARS-CoV-2 receptor binding domain (RBD). Subsequent directed evolution via yeast surface display yielded JS18.1, an antibody with high binding affinity for both the Delta and Kappa RBDs, as well as enhanced binding to other RBDs (wild-type, Alpha, Beta, Gamma, Kappa, and Mu). Notably, JS18.1 (engineered for wild-type and Delta RBDs) exhibits enhanced neutralizing capability against the Omicron variant and binds to RBDs noncompetitively with ACE2, distinguishing it from other previously reported antibodies. This underscores the potential of pre-existing antibodies to neutralize emerging SARS-CoV-2 strains and offers insights into strategies to combat emerging viruses.
期刊介绍:
Molecular Pharmaceutics publishes the results of original research that contributes significantly to the molecular mechanistic understanding of drug delivery and drug delivery systems. The journal encourages contributions describing research at the interface of drug discovery and drug development.
Scientific areas within the scope of the journal include physical and pharmaceutical chemistry, biochemistry and biophysics, molecular and cellular biology, and polymer and materials science as they relate to drug and drug delivery system efficacy. Mechanistic Drug Delivery and Drug Targeting research on modulating activity and efficacy of a drug or drug product is within the scope of Molecular Pharmaceutics. Theoretical and experimental peer-reviewed research articles, communications, reviews, and perspectives are welcomed.