About: Assessment of Proton-Coupled Conformational Dynamics of SARS and MERS Coronavirus Papain-like Proteases: Implication for Designing Broad-Spectrum Antiviral Inhibitors

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

About: Assessment of Proton-Coupled Conformational Dynamics of SARS and MERS Coronavirus Papain-like Proteases: Implication for Designing Broad-Spectrum Antiviral Inhibitors Goto Sponge NotDistinct Permalink

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

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Assessment of Proton-Coupled Conformational Dynamics of SARS and MERS Coronavirus Papain-like Proteases: Implication for Designing Broad-Spectrum Antiviral Inhibitors
Creator	Shen, Jana Henderson, Jack Verma, Neha
source	BioRxiv; Medline; PMC
abstract	Broad-spectrum antiviral drugs are urgently needed to stop the COVID-19 pandemic and prevent future ones. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is related to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), which have caused the previous outbreaks. The papain-like protease (PLpro) is an attractive drug target due to its essential roles in the viral life cycle. As a cysteine protease, PLpro is rich in cysteines and histidines and their protonation/deprotonation modulates catalysis and conformational plasticity. Here we report the pK(a) calculations and assessment of the proton-coupled conformational dynamics of SARS-CoV-2 in comparison to SARS-CoV and MERS-CoV PLpros using a newly developed GPU-accelerated implicit-solvent continuous constant pH molecular dynamics method with an asynchronous replica-exchange scheme. The calculated pK(a)’s support the catalytic roles of the Cys-His-Asp triad. We also found that several residues can switch protonation states at physiological pH, among which is C270/271 located on the flexible blocking loop 2 (BL2) of SARS-CoV-2/CoV PLpro. Simulations revealed that the BL2 conformational dynamics is coupled to the titration of C271/270, in agreement with the crystal structures of SARS-CoV-2 PLpro. Simulations also revealed that BL2 in MERS-CoV PLpro is very flexible, sampling both open and closed states despite the lack of an analogous cysteine. Our work provides a starting point for more detailed mechanistic studies to assist structure-based design of broad-spectrum inhibitors against CoV PLpros.
has issue date	2020-07-01(xsd:dateTime)
bibo:doi	10.1101/2020.06.30.181305
bibo:pmid	32637952
has license	no-cc
sha1sum (hex)	97750e9583f308bda7355427674bdf9c3b8c385b
schema:url	https://doi.org/10.1101/2020.06.30.181305
resource representing a document's title	Assessment of Proton-Coupled Conformational Dynamics of SARS and MERS Coronavirus Papain-like Proteases: Implication for Designing Broad-Spectrum Antiviral Inhibitors
has PubMed Central identifier	PMC7337382
has PubMed identifier	32637952
schema:publication	bioRxiv
resource representing a document's body	covid:97750e9583f308bda7355427674bdf9c3b8c385b#body_text
is schema:about of	named entity 'BL2' named entity 'outbreaks' named entity 'calculated' named entity 'COVID-19' named entity 'switch' named entity 'mechanistic' named entity 'coupled' named entity 'SARS-CoV' named entity 'SARS-CoV-2' named entity 'Assessment' named entity 'ASYNCHRONOUS' named entity 'ITS' named entity 'PROTEASE' named entity 'EXCHANGE' named entity 'NOVEL' named entity 'OPEN' named entity 'STRUCTURE' named entity 'OUTBREAKS' named entity 'COMPARISON' named entity 'PHYSIOLOGICAL' named entity 'CYSTEINE' named entity 'FUTURE' named entity 'CLOSED' named entity 'NEEDED' named entity 'SPECTRUM' named entity 'LIKE' named entity 'STRUCTURES' named entity 'USING' named entity 'DRUG TARGET' named entity 'LACK' named entity 'ACCELERATED' named entity 'TITRATION' covid:arg/97750e9583f308bda7355427674bdf9c3b8c385b named entity 'structure-based design' named entity 'MERS-CoV' named entity 'analogous' named entity 'constant' named entity 'catalysis' named entity 'broad-spectrum' named entity 'drug target' named entity 'PLpro' named entity 'crystal structures' named entity 'physiological pH' named entity 'protease' named entity 'cysteine protease' named entity 'SARS-CoV' named entity 'histidines' named entity 'SARS-CoV' named entity 'proton' named entity 'conformational dynamics' named entity 'SARS' named entity 'Proton' named entity 'Conformational Dynamics' named entity 'pH 7' named entity 'cysteine' named entity 'MERS-CoV' named entity 'MERS-CoV' named entity 'protonated' named entity 'atom' named entity 'SARS-Cov' named entity 'Trp' named entity 'MERS-CoV' named entity 'hydrogen bond' named entity 'Probability distribution' named entity 'hydrogen bond' named entity 'proton' named entity 'SARS-CoV' named entity 'Cys' named entity 'energy minimization' named entity 'hydrogen bonds' named entity 'molecular dynamics' named entity 'hydrogen bond' named entity 'coronaviruses' named entity 'protonated' named entity 'catalytic triad' named entity 'conformation' named entity 'Cys' named entity 'Electronic mail' named entity 'hydrophobic'

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 © 2009-2025 OpenLink Software