Thermodynamic and structural characterization of an optimized peptide-based inhibitor of the influenza polymerase PA-PB1 subunit interaction

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F22%3A00563164" target="_blank" >RIV/61388963:_____/22:00563164 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/22:10448909 RIV/00216208:11310/22:10448909
Result on the web
<a href="https://doi.org/10.1016/j.antiviral.2022.105449" target="_blank" >https://doi.org/10.1016/j.antiviral.2022.105449</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.antiviral.2022.105449" target="_blank" >10.1016/j.antiviral.2022.105449</a>

Result language
angličtina
Original language name
Thermodynamic and structural characterization of an optimized peptide-based inhibitor of the influenza polymerase PA-PB1 subunit interaction
Original language description
Influenza virus causes severe respiratory infection in humans. Current antivirotics target three key proteins in the viral life cycle: neuraminidase, the M2 channel and the endonuclease domain of RNA-dependent-RNA polymerase. Due to the development of novel pandemic strains, additional antiviral drugs targetting different viral proteins are still needed. The protein-protein interaction between polymerase subunits PA and PB1 is one such possible target. We recently identified a modified decapeptide derived from the N-terminus of the PB1 subunit with high affinity for the C-terminal part of the PA subunit. Here, we optimized its amino acid hotspots to maintain the inhibitory potency and greatly increase peptide solubility. This allowed thermodynamic characterization of peptide binding to PA. Solving the X-ray structure of the peptide-PA complex provided structural insights into the interaction. Additionally, we optimized intracellular delivery of the peptide using a bicyclic strategy that led to improved inhibition in cell-based assays.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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