Nebulized delivery of a broadly neutralizing SARS-CoV-2 RBD-specific nanobody prevents clinical, virological, and pathological disease in a Syrian hamster model of COVID-19

Esparza, Thomas J.; Chen, Yaozong; Martin, Negin P.; Bielefeldt-Ohmann, Helle; Bowen, Richard A.; Tolbert, William D.; Pazgier, Marzena; Brody, David L.

doi:10.1080/19420862.2022.2047144

Nebulized delivery of a broadly neutralizing SARS-CoV-2 RBD-specific nanobody prevents clinical, virological, and pathological disease in a Syrian hamster model of COVID-19

Journal Article · Tue Mar 15 00:00:00 EDT 2022 · MAbs

DOI:https://doi.org/10.1080/19420862.2022.2047144· OSTI ID:1903981

Esparza, Thomas J. ^[1]; Chen, Yaozong ^[2]; Martin, Negin P. ^[3]; Bielefeldt-Ohmann, Helle ^[4]; Bowen, Richard A. ^[5]; Tolbert, William D. ^[2]; ^[2]; Brody, David L. ^[6]

Laboratory of Functional and Molecular Imaging (LFMI), Bethesda, MD, (United States); Uniformed Services University of the Health Sciences, Bethesda, MD (United States); Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, Bethesda, MD (United States); OSTI
Uniformed Services University of the Health Sciences, Bethesda, MD (United States)
National Institute of Environmental Health Sciences (NIEHS), Durham, NC (United States)
Univ. of Queensland, St Lucia, QLD (Australia)
Colorado State Univ., Fort Collins, CO (United States)
Laboratory of Functional and Molecular Imaging (LFMI), Bethesda, MD, (United States); Uniformed Services University of the Health Sciences, Bethesda, MD (United States)

There remains an unmet need for globally deployable, low-cost therapeutics for the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Previously, we reported on the isolation and in vitro characterization of a potent single-domain nanobody, NIH-CoVnb-112, specific for the receptor-binding domain (RBD) of SARS-CoV-2. Here, we report on the molecular basis for the observed broad in vitro neutralization capability of NIH-CoVnb-112 against variant SARS-CoV-2 pseudoviruses. The structure of NIH-CoVnb-112 bound to SARS-CoV-2 RBD reveals a large contact surface area overlapping the angiotensin converting enzyme 2 (ACE2) binding site, which is largely unencumbered by the common RBD mutations. In an in vivo pilot study, we demonstrate effective reductions in weight loss, viral burden, and lung pathology in a Syrian hamster model of COVID-19 following nebulized delivery of NIH-CoVnb-112. These findings support the further development of NIH-CoVnb-112 as a potential adjunct preventative therapeutic for the treatment of SARS-CoV-2 infection.

View Accepted Manuscript (DOE)

Research Organization:: SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institute of Neurological Disorders and Stroke (NINDS)

Grant/Contract Number:: AC02-76SF00515

OSTI ID:: 1903981

Journal Information:: MAbs, Journal Name: MAbs Journal Issue: 1 Vol. 14; ISSN 1942-0862

Publisher:: Taylor & FrancisCopyright Statement

Country of Publication:: United States

Language:: English

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60 APPLIED LIFE SCIENCES
COVID-19
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nebulized delivery
neutralizing nanobody
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Nebulized delivery of a broadly neutralizing SARS-CoV-2 RBD-specific nanobody prevents clinical, virological, and pathological disease in a Syrian hamster model of COVID-19

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