COVID-19 brought a scientific revolution since its emergence in Wuhan, China, in December 2019. Initially, the SARS-CoV-2 virus came to attention through its effects on the respiratory system. However, its actions in many other organs also have been discovered almost daily. As enzymes are indispensable to uncountable biochemical reactions in the human body, it is not surprising that some enzymes are of relevance to COVID-19 pathophysiology. Past evidence from SARS-CoV and MERS-CoV outbreaks provided hints about the role of enzymes in SARS-CoV-2 infection. In this setting, ACE-2 is an enzyme of great importance since it is the cell entry receptor for SARS-CoV-2. Clinical data elucidate patterns of enzymatic alterations in COVID-19, which could be associated with organ damage, prognosis, and clinical complications. Further, viral mutations can create new disease behaviors, and these effects are related to the activity of enzymes. This review will discuss the main enzymes related to COVID-19, summarizing the findings on their role in viral entry mechanism, the consequences of their dysregulation, and the effects of SARS-CoV-2 mutations on them.
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http://dx.doi.org/10.1016/j.biochi.2022.01.015 | DOI Listing |
Pept Sci (Hoboken)
November 2024
Department of Pediatrics, Section of Hematology/Oncology, The University of Chicago, Chicago, Illinois 60637, United States of America.
The COVID-19 pandemic drove a uniquely fervent pursuit to explore the potential of peptide, antibody, protein, and small-molecule based antiviral agents against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). The interaction between the SARS-CoV2 spike protein with the angiotensin-converting enzyme 2 (ACE2) receptor that mediates viral cell entry was a particularly interesting target given its well described protein-protein interaction (PPI). This PPI is mediated by an α-helical portion of ACE2 binding to the receptor binding domain (RBD) of the spike protein and thought to be susceptible to blockade through molecular mimicry.
View Article and Find Full Text PDFACS Omega
January 2025
Institute of Bioinformatics and Medical Engineering, School of Electrical and Information Engineering, Jiangsu University of Technology, Changzhou 213001, P.R. China.
The main protease (M) is a pivotal target in the life cycle of feline coronavirus (FCoV), which causes a high mortality feline disease, feline infectious peritonitis (FIP). Virtual screening was performed against the feline coronavirus M to find active compounds with low toxicity from a library of natural products. Eighty-six compounds were selected by using the rank of docking score and binding pose analysis.
View Article and Find Full Text PDFBiofactors
January 2025
Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Japan.
SARS-CoV-2-related proteins, ACE2 and TMPRSS2, are determinants of SARS-CoV-2 infection. Although these proteins are expressed in oral-related tissues, their expression patterns and modulatory mechanisms in the salivary glands remain unknown. We herein showed that full-length ACE2, which has both a fully functional enzyme catalytic site and high-affinity SARS-CoV-2 spike S1-binding sites, was more highly expressed in salivary glands than in oral mucosal epithelial cells and the lungs.
View Article and Find Full Text PDFJ Transl Med
January 2025
Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Beijing, 100730, China.
Background: Immunotherapy is a significant risk factor for severe COVID-19 in multiple myeloma (MM) patients. Understanding how immunotherapies lead to severe COVID-19 is crucial for improving patient outcomes.
Methods: Human protein microarrays were used to examine the expression of 440 protein molecules in MM patients treated with bispecific T-cell engagers (BiTe) (n = 9), anti-CD38 monoclonal antibodies (mAbs) (n = 10), and proteasome inhibitor (PI)-based regimens (n = 10).
Biochemistry (Mosc)
December 2024
National Research Centre "Kurchatov Institute", Moscow, 123182, Russia.
Bacterial and viral RNA polymerases are promising targets for the development of new transcription inhibitors. One of the potential blockers of RNA synthesis is 7,8-dihydro-8-oxo-1,-ethenoadenine (oxo-εA), a synthetic compound that combines two adenine modifications: 8-oxoadenine and 1,-ethenoadenine. In this study, we synthesized oxo-εA triphosphate (oxo-εATP) and showed that it could be incorporated by the RNA-dependent RNA polymerase of SARS-CoV-2 into synthesized RNA opposite template residues A and G in the presence of Mn ions.
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