About: Highly Conserved Homotrimer Cavity Formed by the SARS-CoV-2 Spike Glycoprotein: A Novel Binding Site

Facets (new session)
Description
Metadata
Settings
- owl:sameAs
- Inference Rule:

About: Highly Conserved Homotrimer Cavity Formed by the SARS-CoV-2 Spike Glycoprotein: A Novel Binding Site Goto Sponge NotDistinct Permalink

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

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Highly Conserved Homotrimer Cavity Formed by the SARS-CoV-2 Spike Glycoprotein: A Novel Binding Site
Creator	Haas, Juergen Ball, Kathryn Hupp, Ted Alfaro, Javier Daniels, Alison Kalathiya, Umesh Baginski, Maciej Carragher, Neil Fahraeus, Robin Lisowska, Małgorzata Mayordomo, Marcos Nicholson, Judith Padariya, Monikaben Singh, Ashita
Source	Medline; PMC
abstract	An important stage in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) life cycle is the binding of the spike (S) protein to the angiotensin converting enzyme-2 (ACE2) host cell receptor. Therefore, to explore conserved features in spike protein dynamics and to identify potentially novel regions for drugging, we measured spike protein variability derived from 791 viral genomes and studied its properties by molecular dynamics (MD) simulation. The findings indicated that S2 subunit (heptad-repeat 1 (HR1), central helix (CH), and connector domain (CD) domains) showed low variability, low fluctuations in MD, and displayed a trimer cavity. By contrast, the receptor binding domain (RBD) domain, which is typically targeted in drug discovery programs, exhibits more sequence variability and flexibility. Interpretations from MD simulations suggest that the monomer form of spike protein is in constant motion showing transitions between an “up” and “down” state. In addition, the trimer cavity may function as a “bouncing spring” that may facilitate the homotrimer spike protein interactions with the ACE2 receptor. The feasibility of the trimer cavity as a potential drug target was examined by structure based virtual screening. Several hits were identified that have already been validated or suggested to inhibit the SARS-CoV-2 virus in published cell models. In particular, the data suggest an action mechanism for molecules including Chitosan and macrolides such as the mTOR (mammalian target of Rapamycin) pathway inhibitor Rapamycin. These findings identify a novel small molecule binding-site formed by the spike protein oligomer, that might assist in future drug discovery programs aimed at targeting the coronavirus (CoV) family of viruses.
has issue date	2020-05-14(xsd:dateTime)
bibo:doi	10.3390/jcm9051473
bibo:pmid	32422996
has license	cc-by
sha1sum (hex)	be00d4279129a09d5e46d097e437551fd61e99d1
schema:url	https://doi.org/10.3390/jcm9051473
resource representing a document's title	Highly Conserved Homotrimer Cavity Formed by the SARS-CoV-2 Spike Glycoprotein: A Novel Binding Site
has PubMed Central identifier	PMC7290299
has PubMed identifier	32422996
schema:publication	J Clin Med
resource representing a document's body	covid:be00d4279129a09d5e46d097e437551fd61e99d1#body_text
is schema:about of	named entity 'receptor' named entity 'protein' named entity 'function' named entity 'macrolides' named entity 'molecular dynamics' named entity 'family' named entity 'connector' named entity 'protein' named entity 'infectious disease' named entity 'ACE2' named entity 'Clinical Medicine' named entity 'FINDINGS' named entity 'MD SIMULATIONS' named entity 'ITS' named entity 'MTOR' named entity 'REPEAT' named entity 'SARS-COV-2' named entity 'EXAMINATION' named entity 'CONNECTOR' named entity 'FLEXIBILITY' named entity 'TARGET' named entity 'VIRAL LIFE CYCLE' named entity 'TO IDENTIFY' named entity 'INFECTIOUS DISEASE' named entity 'MOLECULES' named entity 'PROGRAMS' named entity 'SIMULATION' named entity 'TARGETED' named entity 'ASSIST' named entity 'MOTION' named entity 'CORONAVIRUS' covid:arg/be00d4279129a09d5e46d097e437551fd61e99d1 named entity 'cell' named entity 'programs' named entity 'host' named entity 'life cycle' named entity 'spring' named entity 'validated' named entity 'domains' named entity 'HR1' named entity 'viruses' named entity 'domain' named entity 'models' named entity 'regions' named entity 'variability' named entity 'flexibility' named entity 'host cell receptor' named entity 'oligomer' named entity 'infectious disease' named entity 'ACE2 receptor' named entity 'drug discovery' named entity 'molecular dynamics' named entity 'mammalian target of Rapamycin' named entity 'viral genomes' named entity 'drug target' named entity 'SARS-CoV-2' named entity 'Homotrimer' named entity 'enzyme' named entity 'based' named entity 'future' named entity 'spike protein' named entity 'SARS-CoV-2' named entity 'chitosan' named entity 'oligomerization' named entity 'glycoprotein' named entity 'Chemical Computing Group' named entity 'Rapamycin' named entity 'kcal'

Faceted Search & Find service v1.13.91 as of Mar 24 2020

Alternative Linked Data Documents: Sponger | ODE Content Formats:

RDF

ODATA

Microdata

About

OpenLink Virtuoso version 07.20.3229 as of Jul 10 2020, on Linux (x86_64-pc-linux-gnu), Single-Server Edition (94 GB total memory)
Data on this page belongs to its respective rights holders.
Virtuoso Faceted Browser Copyright © 2009-2024 OpenLink Software