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Structure of SARS-CoV-2 MTase nsp14 with the inhibitor STM957 reveals inhibition mechanism that is shared with a poxviral MTase VP39.
J Struct Biol X
December 2024
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic.
Nsp14 is an RNA methyltransferase (MTase) encoded by all coronaviruses. In fact, many viral families, including DNA viruses, encode MTases that catalyze the methylation of the RNA precap structure, resulting in fully capped viral RNA. This capping is crucial for efficient viral RNA translation, stability, and immune evasion.
View Article and Find Full Text PDF7-Deaza-2'-deoxyisoguanosine, a Noncanonical Nucleoside for Nucleic Acid Code Expansion and New DNA Constructs: Nucleobase Functionalization of Inverse Watson-Crick and Purine-Purine Base Pairs.
Bioconjug Chem
August 2024
Laboratory of Bioorganic Chemistry and Chemical Biology, Center for Nanotechnology, Heisenbergstrasse 11, 48149 Münster, Germany.
7-Deaza-2'-deoxyisoguanosine forms stable inverse Watson-Crick base pairs with 5-methyl-2'-deoxyisocytidine and purine-purine base pairs with 2'-deoxyguanosine or 5-aza-7-deaza-2'-deoxyguanosine. Both base pairs expand the genetic coding system. The manuscript reports on the functionalization of these base pairs with halogen atoms and clickable side chains introduced at 7-position of the 7-deazapurine base.
View Article and Find Full Text PDFImproved synthesis and polymerase recognition of 7-deaza-7-modified α-l-threofuranosyl guanosine analogs.
RSC Adv
June 2024
Department of Pharmaceutical Sciences, University of California Irvine CA 92697-3958 USA
Threofuranosyl nucleic acid (TNA), an artificial genetic polymer known for its nuclease resistance and acid stability, has grown in popularity as a genetically-encoded material for applications in synthetic biology and biomedicine. TNA oligonucleotide synthesis requires enzymatic or solid phase synthesis pathways that rely on monomer building blocks that are not commercially available and can only be obtained by chemical synthesis. Here we present a synthetic route to 7-deaza-7-modified tGTP and phosphoramidite analogs that is operationally simpler than our previously described strategy.
View Article and Find Full Text PDFAtomic Mutagenesis of -Methyladenosine Reveals Distinct Recognition Modes by Human mA Reader and Eraser Proteins.
J Am Chem Soc
March 2024
Institute of Organic Chemistry, University of Würzburg, Am Hubland, Würzburg 97074, Germany.
-methyladenosine (mA) is an important modified nucleoside in cellular RNA associated with multiple cellular processes and is implicated in diseases. The enzymes associated with the dynamic installation and removal of mA are heavily investigated targets for drug research, which requires detailed knowledge of the recognition modes of mA by proteins. Here, we use atomic mutagenesis of mA to systematically investigate the mechanisms of the two human mA demethylase enzymes FTO and ALKBH5 and the binding modes of YTH reader proteins YTHDF2/DC1/DC2.
View Article and Find Full Text PDFMolnupiravir inhibits human norovirus and rotavirus replication in 3D human intestinal enteroids.
Antiviral Res
March 2024
KU Leuven, Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, Belgium. Electronic address:
Human norovirus (HuNoV) and human rotavirus (HRV) are the leading causes of gastrointestinal diarrhea. There are no approved antivirals and rotavirus vaccines are insufficient to cease HRV associated mortality. Furthermore, treatment of chronically infected immunocompromised patients is limited to off-label compassionate use of repurposed antivirals with limited efficacy, highlighting the urgent need of potent and specific antivirals for HuNoV and HRV.
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