Myricetin inhibits transmissible gastroenteritis virus replication by targeting papain-like protease deubiquitinating enzyme activity

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 15

Published: July 10, 2024

Myricetin, a natural flavonoid found in various foods, was investigated for its antiviral effect against transmissible gastroenteritis virus (TGEV). This α-coronavirus causes significant economic losses the global swine industry. The study focused on papain-like protease (PLpro), which plays crucial role coronavirus immune evasion by mediating deubiquitination. Targeting PLpro could potentially disrupt viral replication and enhance responses. results demonstrated that myricetin effectively inhibited TGEV-induced cytopathic effects dose-dependent manner, with an EC50 value of 31.19 μM. Myricetin significantly reduced TGEV load within 48 h after 8-h co-incubation period. Further investigations revealed at concentration 100 μM directly inactivated suppressed intracellular stage. Moreover, pretreatment conferred protective PK-15 cells infection. competitively IC50 6.563 Molecular docking experiments show binds to Cys102 residue through conventional hydrogen bonds, Pi-sulfur, Pi-alkyl interactions. binding confirmed site-directed mutagenesis experiments, indicating as potential candidate preventing treating

Language: Английский

A Comparative Analysis of SARS-CoV-2 Variants of Concern (VOC) Spike Proteins Interacting with hACE2 Enzyme

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8032 - 8032

Published: July 23, 2024

In late 2019, the emergence of a novel coronavirus led to its identification as SARS-CoV-2, precipitating onset COVID-19 pandemic. Many experimental and computational studies were performed on SARS-CoV-2 understand behavior patterns. this research, Molecular Dynamic (MD) simulation is utilized compare behaviors Variants Concern (VOC)-Alpha, Beta, Gamma, Delta, Omicron-with hACE2 protein. Protein structures from Data Bank (PDB) aligned trimmed for consistency using Chimera, focusing receptor-binding domain (RBD) responsible ACE2 interaction. MD simulations Visual Dynamics (VMD) Nanoscale (NAMD2), salt bridges hydrogen bond data extracted results these simulations. The last 5 ns 10 visualized, providing insights into comparative stability each variant's interaction with ACE2. Moreover, electrostatics hydrophobic protein surfaces calculated, analyzed. Our comprehensive are helpful drug discovery future vaccine designs they provide information regarding vital amino acids in protein-protein interactions (PPIs). analysis reveals that Original Omicron variants two most structurally similar proteins. Gamma variant forms strongest through bonds, while Alpha Delta form stable bridges; dominated by positive potential binding site, which makes it easy attract receptor; meanwhile, Original, show varying levels both bonds bridges, indicating targeted therapeutic agents can disrupt critical prevent infection.

Language: Английский

Rabbit and Human Angiotensin-Converting Enzyme-2: Structure and Electric Properties

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12393 - 12393

Published: Nov. 19, 2024

The angiotensin-converting enzyme-2 (ACE2) is a transmembrane glycoprotein, consisting of two segments: large carboxypeptidase catalytic domain and small collectrin-like segment. This protein plays an essential role in blood pressure regulation, transforming the peptides angiotensin-I angiotensin-II (vasoconstrictors) into angiotensin-1-9 angiotensin-1-7 (vasodilators). During COVID-19 pandemic, ACE2 became best known as receptor S-protein SARS-CoV-2 coronavirus. purpose following research to reconstruct 3D structure rabbit enzyme rACE2 using its primary amino acid sequence, then compare it with human analog hACE2. For this purpose, we have calculated electric properties thermodynamic stability globules employing computer programs for electrostatics. analysis content sequence demonstrates 85% identity between polypeptide chains. alignment domains enzymes shows coincidence α-helix segments, difference unstructured segments chain. charge rACE2, determined by 70 positively chargeable residues, 114 negatively ones, positive charges Zn

Language: Английский