Therapeutic antibodies, targeting the SARS-CoV-2 spike N-terminal domain, protect lethally infected K18-hACE2 mice

• DOI: 10.1016/j.isci.2021.102479
• Publication Date: 2021-04-26T18:09:18Z
• Authors: Tal Noy-Porat; Adva Mechaly; Yinon Levy; Efi Makdasi; Ron Alcalay; David Gur; Moshe Aftalion; Reut Falach; Shani Leviatan Be...; Shirley Lazar; Ayelet Zauberman; Eyal Epstein; Theodor Chitlaru; Shay Weiss; Hagit Achdout; Jonathan D. Edgew...; Raghavendra Kikkeri; Hai Yu; Xi Chen; Shmuel Yitzhaki; Shmuel C. Shapira; Vered Padler-Kara...; Ohad Mazor; Ronit Rosenfeld
• Keywords: Epitope mapping

Neutralizing antibodies represent a valuable therapeutic approach to countermeasure the current COVID-19 pandemic. Emergence of SARS-CoV-2 variants emphasizes notion that antibody treatments need rely on highly neutralizing monoclonal (mAbs), targeting several distinct epitopes for circumventing therapy escape mutants. Previously, we reported efficient human mAbs recognizing spike receptor-binding domain (RBD) SARS-CoV-2. Here report isolation, characterization, and recombinant production 12 mAbs, three N-terminal virus. Neutralization mechanism these involves receptors other than canonical hACE2 target cells, relying both amino acid N-glycan epitope recognition, suggesting alternative viral cellular portals. Two selected demonstrated full protection K18-hACE2 transgenic mice when administered at low doses late post-exposure, demonstrating high potential infection.