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Comparative and phylogenetic analysis of viruses in the University Hospital Brno
Švestková, Tereza ; Sedlář, Karel (referee) ; Nykrýnová, Markéta (advisor)
This thesis is focused on the SARs-CoV-2 coronavirus associated with severe acute respiratory syndrome, which was first identified in 2019. This coronavirus caused a pandemic that affected almost the entire world. Knowledge of the genetic information is needed for vaccine development, to determine infectivity and to predict the evolution of SARs-CoV-2 variants. To obtain genetic information, RNA must be sequenced and these genomic sequences must be assembled. By comparing the assembled genomes, it is possible to find out which part of the organism has mutated. Phylogenetic analysis is performed on the basis of the concordance or divergence in the assembled genomes, which indicates the evolution of the organism and shows the evolutionary relationship with other organisms. The practical part is focused on the assembly of genomes from samples from patients in the University Hospital Brno and evaluation of the quality of the assembly. After the genomes are assembled, the next goal is to evaluate the variability and subsequent phylogenetic analysis.
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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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Comparative and phylogenetic analysis of viruses in the University Hospital Brno
Švestková, Tereza ; Sedlář, Karel (referee) ; Nykrýnová, Markéta (advisor)
This thesis is focused on the SARs-CoV-2 coronavirus associated with severe acute respiratory syndrome, which was first identified in 2019. This coronavirus caused a pandemic that affected almost the entire world. Knowledge of the genetic information is needed for vaccine development, to determine infectivity and to predict the evolution of SARs-CoV-2 variants. To obtain genetic information, RNA must be sequenced and these genomic sequences must be assembled. By comparing the assembled genomes, it is possible to find out which part of the organism has mutated. Phylogenetic analysis is performed on the basis of the concordance or divergence in the assembled genomes, which indicates the evolution of the organism and shows the evolutionary relationship with other organisms. The practical part is focused on the assembly of genomes from samples from patients in the University Hospital Brno and evaluation of the quality of the assembly. After the genomes are assembled, the next goal is to evaluate the variability and subsequent phylogenetic analysis.
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