About: A Novel Nanobody Targeting Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Receptor-Binding Domain Has Potent Cross-Neutralizing Activity and Protective Efficacy against MERS-CoV

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About: A Novel Nanobody Targeting Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Receptor-Binding Domain Has Potent Cross-Neutralizing Activity and Protective Efficacy against MERS-CoV Goto Sponge NotDistinct Permalink

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Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	A Novel Nanobody Targeting Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Receptor-Binding Domain Has Potent Cross-Neutralizing Activity and Protective Efficacy against MERS-CoV
Creator	Du, Lanying Guo, Yan Jiang, Shibo Zhao, Guangyu Zhou, Yusen Sun, Shihui Gallagher, Tom Tai, Wanbo Li, Fang Shang, Jian Wang, Yufei Li, Chen Chen, Yuehong He, Lei Li, Jiangfan Li, Jiang Qiu, Hongjie Chen, Jiawei Du, Enqi Fan, Ruiwen Ji, Kaiyuan Wang, Guo
Source	Medline; PMC
abstract	The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) continues to infect humans and camels, calling for efficient, cost-effective, and broad-spectrum strategies to control its spread. Nanobodies (Nbs) are single-domain antibodies derived from camelids and sharks and are potentially cost-effective antivirals with small size and great expression yield. In this study, we developed a novel neutralizing Nb (NbMS10) and its human-Fc-fused version (NbMS10-Fc), both of which target the MERS-CoV spike protein receptor-binding domain (RBD). We further tested their receptor-binding affinity, recognizing epitopes, cross-neutralizing activity, half-life, and efficacy against MERS-CoV infection. Both Nbs can be expressed in yeasts with high yield, bind to MERS-CoV RBD with high affinity, and block the binding of MERS-CoV RBD to the MERS-CoV receptor. The binding site of the Nbs on the RBD was mapped to be around residue Asp539, which is part of a conserved conformational epitope at the receptor-binding interface. NbMS10 and NbMS10-Fc maintained strong cross-neutralizing activity against divergent MERS-CoV strains isolated from humans and camels. Particularly, NbMS10-Fc had significantly extended half-life in vivo; a single-dose treatment of NbMS10-Fc exhibited high prophylactic and therapeutic efficacy by completely protecting humanized mice from lethal MERS-CoV challenge. Overall, this study proves the feasibility of producing cost-effective, potent, and broad-spectrum Nbs against MERS-CoV and has produced Nbs with great potentials as anti-MERS-CoV therapeutics. IMPORTANCE Therapeutic development is critical for preventing and treating continual MERS-CoV infections in humans and camels. Because of their small size, nanobodies (Nbs) have advantages as antiviral therapeutics (e.g., high expression yield and robustness for storage and transportation) and also potential limitations (e.g., low antigen-binding affinity and fast renal clearance). Here, we have developed novel Nbs that specifically target the receptor-binding domain (RBD) of MERS-CoV spike protein. They bind to a conserved site on MERS-CoV RBD with high affinity, blocking RBD's binding to MERS-CoV receptor. Through engineering a C-terminal human Fc tag, the in vivo half-life of the Nbs is significantly extended. Moreover, the Nbs can potently cross-neutralize the infections of diverse MERS-CoV strains isolated from humans and camels. The Fc-tagged Nb also completely protects humanized mice from lethal MERS-CoV challenge. Taken together, our study has discovered novel Nbs that hold promise as potent, cost-effective, and broad-spectrum anti-MERS-CoV therapeutic agents.
has issue date	2018-08-29(xsd:dateTime)
bibo:doi	10.1128/jvi.00837-18
bibo:pmid	29950421
has license	cc-by
sha1sum (hex)	69dfbde6c5ed2f0c93261cf763e206f0f3d63132
schema:url	https://doi.org/10.1128/jvi.00837-18
resource representing a document's title	A Novel Nanobody Targeting Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Receptor-Binding Domain Has Potent Cross-Neutralizing Activity and Protective Efficacy against MERS-CoV
has PubMed Central identifier	PMC6146697
has PubMed identifier	29950421
schema:publication	J Virol
resource representing a document's body	covid:69dfbde6c5ed2f0c93261cf763e206f0f3d63132#body_text
is schema:about of	named entity 'expressed' named entity 'cost-effective' named entity 'human' named entity 'tag' named entity 'infections' named entity 'yeasts' named entity 'affinity' named entity 'MERS-CoV' named entity 'humans' named entity 'mapped' named entity 'MERS-CoV' named entity 'antiviral' named entity 'Nanobody' named entity 'TARGETING' named entity 'TAKEN' named entity 'BINDING' named entity 'EFFECTIVE' named entity 'HAVE' named entity 'CROSS' named entity 'HIGH EXPRESSION' named entity 'TAG' named entity 'INFECTIONS' named entity 'TAGGED' named entity 'MAINTAINED' named entity 'POTENTIALS' named entity 'EFFICIENT' named entity 'LIMITATIONS' named entity 'TESTED' named entity 'POTENTIAL' named entity 'HUMANS' named entity 'HTTPS' named entity 'SITE' named entity 'OUR' named entity 'EPITOPE' named entity 'CONSERVED' named entity 'ACTIVITY' named entity 'THEIR' named entity 'LOW' named entity 'TO INFECT' named entity 'STORAGE' named entity 'BINDING SITE' named entity 'FEASIBILITY' named entity 'SINGLE-DOMAIN ANTIBODIES' named entity 'ENGINEERING' named entity 'HIGH' named entity 'THERAPEUTIC' named entity 'ISOLATED' named entity 'ANTIVIRALS' named entity 'CAMELS' named entity 'NEWLY' named entity 'COMPLETELY' named entity 'ITS' named entity 'TRANSPORTATION' named entity 'STRATEGIES' named entity 'RENAL CLEARANCE' named entity 'EXTENDED' named entity 'HALF-LIFE' named entity 'SITE OF' named entity 'YEASTS ' named entity 'STRAINS'

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