Medicinal chemistry of viral polymerases and proteases

0567307 - ÚOCHB 2023 RIV CZ eng A - Abstract
Kožíšek, Milan - Král, Michal - Radilová, Kateřina - Gregor, Jiří - Kotačka, Tomáš - Machara, Aleš - Reiberger, Róbert - Majerová, Taťána - Novotný, Pavel
Medicinal chemistry of viral polymerases and proteases.
Czech Chemical Society Symposium Series. Roč. 20, č. 6 (2022), s. 350-350. ISSN 2336-7202.
[Annual meeting of the National Institute of Virology and Bacteriology (NIVB) /1./. 30.11.2022-02.12.2022, Kutná Hora]
R&D Projects: GA MŠMT(CZ) LX22NPO5103
Institutional support: RVO:61388963
Keywords : viral protease * viral polymerase
OECD category: Virology
http://www.ccsss.cz/index.php/ccsss/issue/view/37/67

The influenza virus causes severe infectious diseases that represents a serious threat to public health. There is an urgent need for the development of new anti-influenza drugs effective against resistant viral strains and different viral subtypes. In this project we plan to study endonuclease and cap-binding small molecule inhibitors, as well as peptide inhibitors targeting protein-protein interaction in viral polymerase. Furthermore, due to the functional and presumed structural similarity between influenza A polymerase and L-protein of the emerging Rift Valley Fever virus (RVFV), we plan to utilize our prior experience1–6to develop and identify novel inhibitors of the endonuclease and polymerase activity of RVFV. This project will thus allow the development of active compounds against these important pathogens.In the second part of the project, we focus on viral proteases which are key enzymes in virion maturation that contribute to viral pathogenesis. Targeting viral proteases represents a viable strategy of antiviral therapy. The main focus of this research objective involves proteases of HIV, SARS-CoV-2, Zika and Dengue viruses. Detailed understanding of regulatory steps during autoactivation of these enzymes, their role in virion maturation and pathogenesis is still lacking. We plan to combine biological, chemical and biophysical approaches to study proteases activation, regulation of maturation, intra and their interactions with low-molecular-weight ligands or other viral and host proteins.
Permanent Link: https://hdl.handle.net/11104/0338568