FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2024771806> ?p ?o ?g. }

• W2024771806 endingPage "e15049" @default.
• W2024771806 startingPage "e15049" @default.
• W2024771806 abstract "Foot-and-Mouth Disease Virus (FMDV) is a picornavirus that infects cloven-hoofed animals and leads to severe losses in livestock production. In the case of an FMD outbreak, emergency vaccination requires at least 7 days to trigger an effective immune response. There are currently no approved inhibitors for the treatment or prevention of FMDV infections.Using a luciferase-based assay we screened a library of compounds and identified seven novel inhibitors of 3Dpol, the RNA-dependent RNA polymerase of FMDV. The compounds inhibited specifically 3Dpol (IC(50)s from 2-17 µM) and not other viral or bacterial polymerases. Enzyme kinetic studies on the inhibition mechanism by compounds 5D9 and 7F8 showed that they are non-competitive inhibitors with respect to NTP and nucleic acid substrates. Molecular modeling and docking studies into the 3Dpol structure revealed an inhibitor binding pocket proximal to, but distinct from the 3Dpol catalytic site. Residues surrounding this pocket are conserved among all 60 FMDV subtypes. Site directed mutagenesis of two residues located at either side of the pocket caused distinct resistance to the compounds, demonstrating that they indeed bind at this site. Several compounds inhibited viral replication with 5D9 suppressing virus production in FMDV-infected cells with EC(50) = 12 µM and EC(90) = 20 µM).We identified several non-competitive inhibitors of FMDV 3Dpol that target a novel binding pocket, which can be used for future structure-based drug design studies. Such studies can lead to the discovery of even more potent antivirals that could provide alternative or supplementary options to contain future outbreaks of FMD." @default.
• W2024771806 created "2016-06-24" @default.
• W2024771806 creator A5003623192 @default.
• W2024771806 creator A5006337398 @default.
• W2024771806 creator A5010028441 @default.
• W2024771806 creator A5011805768 @default.
• W2024771806 creator A5015805528 @default.
• W2024771806 creator A5016248392 @default.
• W2024771806 creator A5031948894 @default.
• W2024771806 creator A5040009915 @default.
• W2024771806 creator A5048305174 @default.
• W2024771806 creator A5049782797 @default.
• W2024771806 creator A5054688016 @default.
• W2024771806 creator A5061744168 @default.
• W2024771806 creator A5073716313 @default.
• W2024771806 creator A5074343525 @default.
• W2024771806 creator A5078734256 @default.
• W2024771806 creator A5079545175 @default.
• W2024771806 creator A5081748856 @default.
• W2024771806 date "2010-12-21" @default.
• W2024771806 modified "2023-09-23" @default.
• W2024771806 title "Inhibitors of Foot and Mouth Disease Virus Targeting a Novel Pocket of the RNA-Dependent RNA Polymerase" @default.
• W2024771806 cites W1567952953 @default.
• W2024771806 cites W1744409238 @default.
• W2024771806 cites W1817236034 @default.
• W2024771806 cites W1969118676 @default.
• W2024771806 cites W1975106131 @default.
• W2024771806 cites W1976534088 @default.
• W2024771806 cites W1991001144 @default.
• W2024771806 cites W1991492628 @default.
• W2024771806 cites W2003803262 @default.
• W2024771806 cites W2012916378 @default.
• W2024771806 cites W2014119797 @default.
• W2024771806 cites W2017436619 @default.
• W2024771806 cites W2023016206 @default.
• W2024771806 cites W2023089361 @default.
• W2024771806 cites W2026034630 @default.
• W2024771806 cites W2026065136 @default.
• W2024771806 cites W2027166401 @default.
• W2024771806 cites W2036465650 @default.
• W2024771806 cites W2037691295 @default.
• W2024771806 cites W2037772484 @default.
• W2024771806 cites W2042234088 @default.
• W2024771806 cites W2050495992 @default.
• W2024771806 cites W2050747066 @default.
• W2024771806 cites W2053792903 @default.
• W2024771806 cites W2067939631 @default.
• W2024771806 cites W2069622512 @default.
• W2024771806 cites W2071605848 @default.
• W2024771806 cites W2072041078 @default.
• W2024771806 cites W2074454030 @default.
• W2024771806 cites W2087940972 @default.
• W2024771806 cites W2089387552 @default.
• W2024771806 cites W2091902745 @default.
• W2024771806 cites W2100886241 @default.
• W2024771806 cites W2103554874 @default.
• W2024771806 cites W2110670926 @default.
• W2024771806 cites W2114430694 @default.
• W2024771806 cites W2116262829 @default.
• W2024771806 cites W2123050578 @default.
• W2024771806 cites W2125923988 @default.
• W2024771806 cites W2126589642 @default.
• W2024771806 cites W2128402268 @default.
• W2024771806 cites W2135732933 @default.
• W2024771806 cites W2138524557 @default.
• W2024771806 cites W2139630684 @default.
• W2024771806 cites W2151535433 @default.
• W2024771806 cites W2159808261 @default.
• W2024771806 cites W2317554121 @default.
• W2024771806 cites W2322441340 @default.
• W2024771806 doi "https://doi.org/10.1371/journal.pone.0015049" @default.
• W2024771806 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3006429" @default.
• W2024771806 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21203539" @default.
• W2024771806 hasPublicationYear "2010" @default.
• W2024771806 type Work @default.
• W2024771806 sameAs 2024771806 @default.
• W2024771806 citedByCount "21" @default.
• W2024771806 countsByYear W20247718062012 @default.
• W2024771806 countsByYear W20247718062013 @default.
• W2024771806 countsByYear W20247718062014 @default.
• W2024771806 countsByYear W20247718062015 @default.
• W2024771806 countsByYear W20247718062016 @default.
• W2024771806 countsByYear W20247718062018 @default.
• W2024771806 countsByYear W20247718062019 @default.
• W2024771806 countsByYear W20247718062020 @default.
• W2024771806 crossrefType "journal-article" @default.
• W2024771806 hasAuthorship W2024771806A5003623192 @default.
• W2024771806 hasAuthorship W2024771806A5006337398 @default.
• W2024771806 hasAuthorship W2024771806A5010028441 @default.
• W2024771806 hasAuthorship W2024771806A5011805768 @default.
• W2024771806 hasAuthorship W2024771806A5015805528 @default.
• W2024771806 hasAuthorship W2024771806A5016248392 @default.
• W2024771806 hasAuthorship W2024771806A5031948894 @default.
• W2024771806 hasAuthorship W2024771806A5040009915 @default.
• W2024771806 hasAuthorship W2024771806A5048305174 @default.
• W2024771806 hasAuthorship W2024771806A5049782797 @default.
• W2024771806 hasAuthorship W2024771806A5054688016 @default.
• W2024771806 hasAuthorship W2024771806A5061744168 @default.

• next