An all-atom, active site exploration of antiviral drugs that target Flaviviridae polymerases

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F16%3AN0000037" target="_blank" >RIV/00027162:_____/16:N0000037 - isvavai.cz</a>
Alternative codes found
RIV/60077344:_____/16:00468801 RIV/60076658:12310/16:43891958
Result on the web
<a href="http://jgv.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.000569" target="_blank" >http://jgv.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.000569</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1099/jgv.0.000569" target="_blank" >10.1099/jgv.0.000569</a>

Result language
angličtina
Original language name
An all-atom, active site exploration of antiviral drugs that target Flaviviridae polymerases
Original language description
Natural 2'-modified nucleosides are the most widely used antiviral therapy. In their triphosphorylated form, a.k.a. nucleotide analogues target the active site of viral polymerases. Viral polymerases have an overall right handed structure that include the palm, fingers and thumb domains. These domains are further subdivided into structurally conserved motifs A-G common to all viral polymerases. The structural motifs encapsulate the allosteric/initiation (N1) and orthosteric/catalytic (N2) nucleotide-binding sites. The current study investigated how nucleotide analogues explore the N2 site of viral polymerases from three genera of the Flaviviridae family using a stochastic, biophysical, Metropolis Monte Carlo-based software. The biophysical simulations showed a statistical distinction in nucleotide binding energy and exploration between phylogenetically related viral polymerases. This distinction is clearly demonstrated by the respective analogue contacts made with conserved viral polymerase residues, the heterogeneous dynamics of structural motifs, and the orientation of the nucleotide analogues within the N2 site. Being able to simulate what occurs within viral polymerase binding sites can prove useful in rational drug designs against viruses.
Czech name
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Czech description
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Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
EE - Microbiology, virology
OECD FORD branch
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Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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