tetano
Editor, Senior Moderator
MAbs
. Jan-Dec 2022;14(1):2047144.
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
Thomas J Esparza[SUP] 1 2 3 [/SUP], Yaozong Chen[SUP] 4 [/SUP], Negin P Martin[SUP] 5 6 [/SUP], Helle Bielefeldt-Ohmann[SUP] 7 [/SUP], Richard A Bowen[SUP] 8 [/SUP], William D Tolbert[SUP] 4 [/SUP], Marzena Pazgier[SUP] 4 [/SUP], David L Brody[SUP] 1 2 9 [/SUP]
Affiliations
Abstract
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.Abbreviations: ACE2 - angiotensin converting enzyme 2BSA - buried surface areaCDR - complementary determining regionRBD - receptor binding domainRBM - receptor-binding motifSARS-CoV-2 - severe acute respiratory syndrome coronavirus 2.
Keywords: COVID-19; SARS-CoV-2; nebulized delivery; neutralizing nanobody; single-domain antibody.
. Jan-Dec 2022;14(1):2047144.
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
Thomas J Esparza[SUP] 1 2 3 [/SUP], Yaozong Chen[SUP] 4 [/SUP], Negin P Martin[SUP] 5 6 [/SUP], Helle Bielefeldt-Ohmann[SUP] 7 [/SUP], Richard A Bowen[SUP] 8 [/SUP], William D Tolbert[SUP] 4 [/SUP], Marzena Pazgier[SUP] 4 [/SUP], David L Brody[SUP] 1 2 9 [/SUP]
Affiliations
- PMID: 35289719
- PMCID: PMC8928829
- DOI: 10.1080/19420862.2022.2047144
Abstract
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.Abbreviations: ACE2 - angiotensin converting enzyme 2BSA - buried surface areaCDR - complementary determining regionRBD - receptor binding domainRBM - receptor-binding motifSARS-CoV-2 - severe acute respiratory syndrome coronavirus 2.
Keywords: COVID-19; SARS-CoV-2; nebulized delivery; neutralizing nanobody; single-domain antibody.