About: Identification of 6′-β-fluoro-homoaristeromycin as a potent inhibitor of chikungunya virus replication

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

About: Identification of 6′-β-fluoro-homoaristeromycin as a potent inhibitor of chikungunya virus replication 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
has title	Identification of 6′-β-fluoro-homoaristeromycin as a potent inhibitor of chikungunya virus replication
Creator	Chang, Tong-Shin Kim, Gyudong Kim, Hong-Rae Kovacikova, Kristina Jang, Min Jarhad, Dnyandev Jeong, Lak Shin, Young Van Hemert, Martijn Yoon, Ji-Seong Hyun, Young Tipnis, Amol
Source	Elsevier; Medline; PMC
abstract	Abstract We have reported on aristeromycin (1) and 6′-fluorinated-aristeromycin analogues (2), which are active against RNA viruses such as Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), Zika virus (ZIKV), and Chikungunya virus (CHIKV). However, these exhibit substantial cytotoxicity. As this cytotoxicity may be attributed to 5′-phosphorylation, we designed and synthesized one-carbon homologated 6′-fluorinated-aristeromycin analogues. This modification prevents 5′-phosphorlyation by cellular kinases, whereas the inhibitory activity towards S-adenosyl-l-homocysteine (SAH) hydrolase will be retained. The enantiomerically pure 6′-fluorinated-5′-homoaristeromycin analogues 3a-e were synthesized via the electrophilic fluorination of the silyl enol ether with Selectfluor, using a base-build up approach as the key steps. All synthesized compounds exhibited potent inhibitory activity towards SAH hydrolase, among which 6′-β-fluoroadenosine analogue 3a was the most potent (IC50 = 0.36 μM). Among the compounds tested, 6′-β-fluoro-homoaristeromycin 3a showed potent antiviral activity (EC50 = 0.12 μM) against the CHIKV, without noticeable cytotoxicity up to 250 μM. Only 3a displayed anti-CHIKV activity, whereas both3a and 3b inhibited SAH hydrolase with similar IC50 values (0.36 and 0.37 μM, respectively), which suggested that 3a’s antiviral activity did not merely depend on the inhibition of SAH hydrolase. This is further supported by the fact that the antiviral effect was specific for CHIKV and some other alphaviruses and none of the homologated analogues inhibited other RNA viruses, such as SARS-CoV, MERS-CoV, and ZIKV. The potent inhibition and high selectivity index make 6′-β-fluoro-homoaristeromycin (3a) a promising new template for the development of antivirals against CHIKV, a serious re-emerging pathogen that has infected millions of people over the past 15 years.
has issue date	2020-02-01(xsd:dateTime)
bibo:doi	10.1016/j.ejmech.2019.111956
bibo:pmid	31841728
has license	els-covid
sha1sum (hex)	57104097c3644dae34bb5a10720fcfe662f753ea
schema:url	https://doi.org/10.1016/j.ejmech.2019.111956
resource representing a document's title	Identification of 6′-β-fluoro-homoaristeromycin as a potent inhibitor of chikungunya virus replication
has PubMed Central identifier	PMC7115507
has PubMed identifier	31841728
schema:publication	European Journal of Medicinal Chemistry
resource representing a document's body	covid:57104097c3644dae34bb5a10720fcfe662f753ea#body_text
is schema:about of	named entity 'FLUORO' named entity '0.12' named entity 'SUPPORTED' named entity 'INDEX' named entity '0.37' named entity 'YEARS' named entity 'INHIBITORY ACTIVITY' named entity 'MAY BE' named entity 'SPECIFIC' named entity 'KINASES' named entity 'MODIFICATION' named entity 'FLUORINATION' named entity 'DISPLAYED' named entity 'CHIKUNGUNYA VIRUS' named entity 'DID' named entity 'MILLIONS' named entity 'SELECTIVITY' named entity 'PREVENTS' named entity 'PHOSPHORYLATION' named entity 'NEW' named entity 'REPORTED' named entity 'SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS' named entity 'STEPS' named entity 'MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS' named entity 'ZIKA VIRUS' named entity 'EFFECT' named entity 'CELLULAR' named entity 'SIMILAR' named entity 'INHIBITED' named entity 'HIGH' named entity 'CHIKUNGUNYA VIRUS' named entity 'ARISTEROMYCIN' named entity 'S-ADENOSYL-L-HOMOCYSTEINE' named entity 'SELECTFLUOR' named entity 'KEY' named entity 'BUILD' named entity 'ACTIVE' named entity 'BASE' named entity 'VIRUS REPLICATION' named entity 'INHIBITOR' named entity 'IDENTIFICATION' named entity 'ANTIVIRALS' named entity 'SAH' named entity '27S' named entity 'CARBON' named entity 'HAVE' named entity 'SARS-COV' named entity 'HYDROLASE' named entity 'TEMPLATE' named entity 'PAST' named entity 'PEOPLE' named entity 'ALPHAVIRUSES' named entity 'RE-EMERGING PATHOGEN' named entity 'INFECTED' named entity 'RETAINED' named entity '282' named entity 'UP TO' named entity 'MAKE' named entity 'FACT' named entity 'ACTIVITY' named entity 'DEPEND' named entity '250' named entity 'TESTED' named entity 'PURE' named entity 'ANALOGUE' named entity 'RNA VIRUSES' named entity 'ANTIVIRAL ACTIVITY' named entity 'SILYL ENOL ETHER' named entity 'VALUES' named entity 'SYNTHESIZED'

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