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National Repository of Grey Literature 2 records found  Search took 0.00 seconds. 
Methyltransferases of human +ssRNA viruses
 Skořepa, Jan ; Bouřa, Evžen (advisor) ; Otava, Tomáš (referee)
The aim of this bachelor's thesis is a structural and functional description of viral methyltransferases of important human +ssRNA viruses from the families Coronaviridae and Flaviviridae. Over 400 million people are infected with diseases such as Dengue, Yellow fever, or Japanese encephalitis (Flaviviridae) every year. During the current pandemic of the SARS-CoV-2 virus (Coronaviridae), more than 750 million people have already been infected worldwide. Methyltransferases are involced in the synthesiz of the cap structure at the 5' end of the viral RNA, which increases its stability and facilitates translation. A detailed structural understanding of proteins NS5 (Flaviviridae methyltransferase), nsp14 and nsp16 (Coronaviridae methyltransferases) is necessary for the subsequent development of their inhibitors. As antivirals, these could help with the treatment of viral diseases caused by coronaviruses and flaviviruses.
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Design and evaluation of potential viral methyltransferase inhibitors
 Kocek, Hugo ; Nencka, Radim (advisor) ; Grantz Šašková, Klára (referee)
A global pandemic of SARS-CoV-2 confirmed the pandemic potential of the Coronaviridae family and pointed out the need for novel antiviral drugs. The SARS-CoV-2 pandemic has been tamed thanks to mRNA vaccines; however, monoclonal antibodies and small molecules such as nirmatrelvir (protease inhibitor), remdesivir (polymerase inhibitor), or molnupiravir (mutagen) are currently also available. It is worth noting that remdesivir and molnupiravir were previously investigated as antivirals against different pathogens. SARS-CoV-2 encodes 16 non-structural proteins, and two of them - methyltransferases (MTases) nsp14 and nsp16 - participate in RNA capping as the virus must mimic the host's mRNA to evade the cellular antiviral sensors (e.g., IFIT1) and replicate. These MTases are structurally very similar to those of SARS-Co-V; therefore, we might expect that inhibitors of SARS-CoV-2 MTases could be used in the future against different coronaviruses. For the reasons mentioned above, this thesis focuses on developing novel MTase inhibitors targeting SARS-CoV-2 nsp14 and nsp16. The design was based on S-adenosyl-L-homocysteine (SAH; endogenous inhibitor of MTases) and an in silico compound library was constructed with various replacements for SAH's amino acid moiety. The potential inhibitory activity was...
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