Publications by authors named "T D Meek"
SARS-CoV-2 3CL protease (Main protease) and human cathepsin L are proteases that play unique roles in the infection of human cells by SARS-CoV-2, the causative agent of COVID-19. Both proteases recognize leucine and other hydrophobic amino acids at the P position of a peptidomimetic inhibitor. At the P position, cathepsin L accepts many amino acid side chains, with a partial preference for phenylalanine, while 3CL-PR protease has a stringent specificity for glutamine or glutamine analogues.
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- The 3-chymotrypsin-like protease (3CL-PR) of SARS-CoV-2 is essential for virus replication and is targeted by the COVID-19 drug Paxlovid, making it important for understanding its catalytic behavior.
- Research indicates that the activity of 3CL-PR is pH-dependent, with specific acidic and basic groups necessary for optimal enzymatic function, suggesting a neutral catalytic dyad involving cysteine and histidine.
- Kinetic studies reveal faster rates in certain conditions, highlighting the influence of the active form of the enzyme, and a full catalytic mechanism for 3CL-PR is proposed based on these findings.
The methyltransferase complex (MTC) deposits N6-adenosine (mA) onto RNA, whereas the microprocessor produces microRNA. Whether and how these two distinct complexes cross-regulate each other has been poorly studied. Here we report that the MTC subunit B tends to form insoluble condensates with poor activity, with its level monitored by the 20S proteasome.
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- The main protease (M) of SARS-CoV-2 is crucial for the virus's maturation and is the target of the COVID-19 treatment Paxlovid, but there's a pressing need to find new inhibitors due to potential viral resistance.
- The study utilized advanced techniques like native mass spectrometry and UV photodissociation to analyze the structure of M and how it interacts with potential covalent inhibitors.
- Results indicated that certain inhibitors enhance the stability of M by creating dimeric complexes with higher melting temperatures and lower charge states, providing valuable insights into how these inhibitors work.