About: Generation of a Nebulizable CDR-Modified MERS-CoV Neutralizing Human Antibody

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An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Generation of a Nebulizable CDR-Modified MERS-CoV Neutralizing Human Antibody
Creator	Kim, Sujeong Kim, Jinhee Min, Ji-Young Kim, Seungtaek Chung, Junho Oh, Myoung-Don Baek, Songyi Jin, Jongwha Lim, Chungsu Chang, So Kim, Sang Park, Wan Shim, Jung
source	Medline; PMC
abstract	Middle East respiratory syndrome coronavirus (MERS-CoV) induces severe aggravating respiratory failure in infected patients, frequently resulting in mechanical ventilation. As limited therapeutic antibody is accumulated in lung tissue following systemic administration, inhalation is newly recognized as an alternative, possibly better, route of therapeutic antibody for pulmonary diseases. The nebulization process, however, generates diverse physiological stresses, and thus, the therapeutic antibody must be resistant to these stresses, remain stable, and form minimal aggregates. We first isolated a MERS-CoV neutralizing antibody that is reactive to the receptor-binding domain (RBD) of spike (S) glycoprotein. To increase stability, we introduced mutations into the complementarity-determining regions (CDRs) of the antibody. In the HCDRs (excluding HCDR3) in this clone, two hydrophobic residues were replaced with Glu, two residues were replaced with Asp, and four residues were replaced with positively charged amino acids. In LCDRs, only two Leu residues were replaced with Val. These modifications successfully generated a clone with significantly greater stability and equivalent reactivity and neutralizing activity following nebulization compared to the original clone. In summary, we generated a MERS-CoV neutralizing human antibody that is reactive to recombinant MERS-CoV S RBD protein for delivery via a pulmonary route by introducing stabilizing mutations into five CDRs.
has issue date	2019-10-12(xsd:dateTime)
bibo:doi	10.3390/ijms20205073
bibo:pmid	31614869
has license	cc-by
sha1sum (hex)	413d8c5b923d8572615bfb6d7199dad41f4ad370
schema:url	https://doi.org/10.3390/ijms20205073
resource representing a document's title	Generation of a Nebulizable CDR-Modified MERS-CoV Neutralizing Human Antibody
has PubMed Central identifier	PMC6829326
has PubMed identifier	31614869
schema:publication	Int J Mol Sci
resource representing a document's body	covid:413d8c5b923d8572615bfb6d7199dad41f4ad370#body_text
is schema:about of	named entity 'MODIFIED' named entity 'CDR' covid:arg/413d8c5b923d8572615bfb6d7199dad41f4ad370 named entity 'ANTIBODY' named entity 'SYSTEMIC ADMINISTRATION' named entity 'SEVERE' named entity 'REGIONS' named entity 'TO INCREASE' named entity 'RECEPTOR' named entity 'INTRODUCED' named entity 'DIVERSE' named entity 'STABILITY' named entity 'RESISTANT TO' named entity 'PROTEIN ' named entity 'LEU' named entity 'GENERATED' named entity 'RESULTING IN' named entity 'AGGREGATES' named entity 'SPIKE' named entity 'RECOMBINANT' named entity 'HUMAN' named entity 'FOLLOWING' named entity 'STABLE' named entity 'RBD' named entity 'ACTIVITY' named entity 'ALTERNATIVE' named entity 'GREATER' named entity 'REPLACED' named entity 'PHYSIOLOGICAL' named entity 'INHALATION' named entity 'INFECTED' named entity 'CDRS' named entity 'AMINO ACIDS' named entity 'RESPIRATORY FAILURE' named entity 'EQUIVALENT' named entity 'CLONE' named entity 'GLYCOPROTEIN' named entity 'THESE' named entity 'GENERATION' named entity 'MERS-COV' named entity 'STABILIZING' named entity 'ACCUMULATED' named entity 'PATIENTS' named entity 'MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS' named entity 'STRESSES' named entity 'GLU' named entity 'ISOLATED' named entity 'POSITIVELY CHARGED' named entity 'NEUTRALIZING ANTIBODY' named entity 'AGGRAVATING' named entity 'DELIVERY' named entity 'ROUTE' named entity 'ANTIBODY' named entity 'BINDING' named entity 'VAL' named entity 'ASP' named entity 'HUMAN' named entity 'FORM' named entity '28S' named entity 'ORIGINAL' named entity 'REACTIVITY' named entity 'PROCESS' named entity 'MECHANICAL VENTILATION' named entity 'FREQUENTLY' named entity 'LUNG TISSUE' named entity 'PULMONARY' named entity 'LIMITED' named entity 'MUTATIONS' named entity 'HYDROPHOBIC'

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