Medicine and Health

Variant-proof high affinity ACE2 antagonist limits SARS-CoV-2 replication in upper and lower airways

M. Gagne, B. J. Flynn, et al.

This groundbreaking study explores the innovative use of aerosolized RBD-62 to combat SARS-CoV-2 Delta in rhesus macaques, demonstrating its ability to suppress viral replication while preserving immune responses. Conducted by a team of expert researchers, this work offers proof-of-concept for novel therapeutics that could prevent severe illnesses from emerging variants.

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Playback language: English

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Abstract

SARS-CoV-2's capacity to evolve mutations that escape vaccine- and infection-acquired immunity and antiviral drugs necessitates variant-agnostic therapeutics. This study challenges rhesus macaques with SARS-CoV-2 Delta, treating them with aerosolized RBD-62 (a protein with 100-fold enhanced ACE2 binding affinity). RBD-62 suppressed virus replication in both upper and lower airways without inhibiting virus-specific T- and B-cell responses or eliciting anti-drug immunity, providing proof-of-concept for preventing severe disease from highly virulent variants.

Publisher

Nature Communications

Published On

Aug 12, 2024

Authors

Matthew Gagne, Barbara J. Flynn, Christopher Cole Honeycutt, Dillon R. Flebb, Shayne F. Andrew, Samantha J. Provost, Lauren McCormick, Alex Van Ry, Elizabeth McCarthy, John-Paul M. Todd, Sanan Bao, Ling Teng, Shari Marciano, Yinon Rudich, Chunlin Li, Shilpi Jain, Bashra Wali, Laurent Pessaint, Alan Dodson, Anthony Cook, Mark G. Lewis, Hanne Andersen, Jiří Zahrādník, Mehul S. Suthar, Martha C. Nason, Kathryn E. Foulds, Peter D. Kwong, Mario Roederer, Gideon Schreiber, Robert A. Seder, Daniel C. Douek

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