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A Novel Human Neutralizing mAb Recognizes Delta, Gamma and Omicron Variants of SARS-CoV-2 and Can Be Used in Combination with Sotrovimab.
Passariello, Margherita; Ferrucci, Veronica; Sasso, Emanuele; Manna, Lorenzo; Lembo, Rosa Rapuano; Pascarella, Stefano; Fusco, Giovanna; Zambrano, Nicola; Zollo, Massimo; De Lorenzo, Claudia.
  • Passariello M; Ceinge-Biotecnologie Avanzate s.c.a.r.l., Via Gaetano Salvatore 486, 80145 Naples, Italy.
  • Ferrucci V; Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Via Pansini 5, 80131 Naples, Italy.
  • Sasso E; Ceinge-Biotecnologie Avanzate s.c.a.r.l., Via Gaetano Salvatore 486, 80145 Naples, Italy.
  • Manna L; Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Via Pansini 5, 80131 Naples, Italy.
  • Lembo RR; Ceinge-Biotecnologie Avanzate s.c.a.r.l., Via Gaetano Salvatore 486, 80145 Naples, Italy.
  • Pascarella S; Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Via Pansini 5, 80131 Naples, Italy.
  • Fusco G; Ceinge-Biotecnologie Avanzate s.c.a.r.l., Via Gaetano Salvatore 486, 80145 Naples, Italy.
  • Zambrano N; Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Via Pansini 5, 80131 Naples, Italy.
  • Zollo M; Ceinge-Biotecnologie Avanzate s.c.a.r.l., Via Gaetano Salvatore 486, 80145 Naples, Italy.
  • De Lorenzo C; European School of Molecular Medicine, University of Milan, 20122 Milan, Italy.
Int J Mol Sci ; 23(10)2022 May 16.
Article in English | MEDLINE | ID: covidwho-1855647
ABSTRACT
The dramatic experience with SARS-CoV-2 has alerted the scientific community to be ready to face new epidemics/pandemics caused by new variants. Among the therapies against the pandemic SARS-CoV-2 virus, monoclonal Antibodies (mAbs) targeting the Spike glycoprotein have represented good drugs to interfere in the Spike/ Angiotensin Converting Enzyme-2 (ACE-2) interaction, preventing virus cell entry and subsequent infection, especially in patients with a defective immune system. We obtained, by an innovative phage display selection strategy, specific binders recognizing different epitopes of Spike. The novel human antibodies specifically bind to Spike-Receptor Binding Domain (RBD) in a nanomolar range and interfere in the interaction of Spike with the ACE-2 receptor. We report here that one of these mAbs, named D3, shows neutralizing activity for virus infection in cell cultures by different SARS-CoV-2 variants and retains the ability to recognize the Omicron-derived recombinant RBD differently from the antibodies Casirivimab or Imdevimab. Since anti-Spike mAbs, used individually, might be unable to block the virus cell entry especially in the case of resistant variants, we investigated the possibility to combine D3 with the antibody in clinical use Sotrovimab, and we found that they recognize distinct epitopes and show additive inhibitory effects on the interaction of Omicron-RBD with ACE-2 receptor. Thus, we propose to exploit these mAbs in combinatorial treatments to enhance their potential for both diagnostic and therapeutic applications in the current and future pandemic waves of coronavirus.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Prognostic study Topics: Variants Limits: Humans Language: English Year: 2022 Document Type: Article Affiliation country: Ijms23105556

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Prognostic study Topics: Variants Limits: Humans Language: English Year: 2022 Document Type: Article Affiliation country: Ijms23105556