8EL2

SARS-CoV-2 RBD bound to neutralizing antibody Fab ICO-hu23

Summary for 8EL2

• Entry DOI: 10.2210/pdb8el2/pdb
• Descriptor: Fab ICO-hu23 Heavy Chain, Fab ICO-hu23 Light Chain, Spike protein S1, ... (6 entities in total)
• Functional Keywords: fab, sars-cov-2, receptor-binding domain, neutralizing antibody, antiviral protein, antiviral protein-immune system complex, antiviral protein/immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 149539.57

Authors

Besaw, J.E.,Kuo, A.,Morizumi, T.,Ernst, O.P. (deposition date: 2022-09-22, release date: 2023-07-19, Last modification date: 2024-10-09)

Primary citation

Hermet, P.,Delache, B.,Herate, C.,Wolf, E.,Kivi, G.,Juronen, E.,Mumm, K.,Zusinaite, E.,Kainov, D.,Sankovski, E.,Virumae, K.,Planken, A.,Merits, A.,Besaw, J.E.,Yee, A.W.,Morizumi, T.,Kim, K.,Kuo, A.,Berriche, A.,Dereuddre-Bosquet, N.,Sconosciuti, Q.,Naninck, T.,Relouzat, F.,Cavarelli, M.,Ustav, M.,Wilson, D.,Ernst, O.P.,Mannik, A.,LeGrand, R.,Ustav Jr., M.
Broadly neutralizing humanized SARS-CoV-2 antibody binds to a conserved epitope on Spike and provides antiviral protection through inhalation-based delivery in non-human primates.
Plos Pathog., 19:e1011532-e1011532, 2023

PubMed Abstract: The COVID-19 pandemic represents a global challenge that has impacted and is expected to continue to impact the lives and health of people across the world for the foreseeable future. The rollout of vaccines has provided highly anticipated relief, but effective therapeutics are required to further reduce the risk and severity of infections. Monoclonal antibodies have been shown to be effective as therapeutics for SARS-CoV-2, but as new variants of concern (VoC) continue to emerge, their utility and use have waned due to limited or no efficacy against these variants. Furthermore, cumbersome systemic administration limits easy and broad access to such drugs. As well, concentrations of systemically administered antibodies in the mucosal epithelium, a primary site of initial infection, are dependent on neonatal Fc receptor mediated transport and require high drug concentrations. To reduce the viral load more effectively in the lung, we developed an inhalable formulation of a SARS-CoV-2 neutralizing antibody binding to a conserved epitope on the Spike protein, ensuring pan-neutralizing properties. Administration of this antibody via a vibrating mesh nebulization device retained antibody integrity and resulted in effective distribution of the antibody in the upper and lower respiratory tract of non-human primates (NHP). In comparison with intravenous administration, significantly higher antibody concentrations can be obtained in the lung, resulting in highly effective reduction in viral load post SARS-CoV-2 challenge. This approach may reduce the barriers of access and uptake of antibody therapeutics in real-world clinical settings and provide a more effective blueprint for targeting existing and potentially emerging respiratory tract viruses.

PubMed: 37531329
DOI: 10.1371/journal.ppat.1011532

Experimental method

X-RAY DIFFRACTION (2.89 Å)