PHE377 / PharmaEssentia - LARVOL DELTA

Molecular mechanistic exploration of conformational shifts induced by class IV anti-RBD antibody IY2A. (PubMed, Int J Biol Macromol) - "Following unfolding, IY2A interacts with the RBD via interatomic hydrogen bonds and hydrophobic contacts involving LEU368, PHE377, LYS378, and SER383. This study provides theoretical insights to guide the development of Class IV antibodies against emerging and future Omicron variants."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Discovery of small molecule entry inhibitors targeting the linoleic acid binding pocket of SARS-CoV-2 spike protein. (PubMed, J Biomol Struct Dyn) - "These molecules showed stable binding on MD simulations over 100 ns and maintained stable interactions with TYR365, PHE338, PHE342, PHE377, TYR369, PHE374 and LEU368 of the spike protein RBD that are found to be conserved among SARS-CoV-2 variants. Our findings were further validated with free energy landscape, principal component analysis and dynamic cross-correlation analysis. Our in silico analysis of binding mode and MD simulation analyses suggest that the identified compounds may impede viral entrance by interacting with the linoleic acid binding site of the spike protein of SARS-CoV-2 regardless of its variants, and they thus demand for further in vitro and in vivo research.Communicated by Ramaswamy H. Sarma."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Discovery, Synthesis, and In Vitro Characterization of 2,3 Derivatives of 4,5,6,7-Tetrahydro-Benzothiophene as Potent Modulators of Retinoic Acid Receptor-Related Orphan Receptor γt. (PubMed, J Med Chem) - "Independent of the two mechanisms, we observed a basal modulatory activity of the tested 2,3 derivatives of 4,5,6,7-tetrahydro-benzothiophene toward RORγt due to the interactions with the Cys320-Glu326 and Arg364-Phe377 hydrophilic regions. The drug discovery approach reported in the current study can be employed to discover modulators of nuclear receptors and other globular protein targets."

Journal • Preclinical • Immunology • Metabolic Disorders • Oncology • ABCB1

A novel shark single-domain antibody targeting OGT as a tool for detection and intracellular localization. (PubMed, Front Immunol) - "VNAR 3F7 was predicted to bind the amino acid residues of Ser375, Phe377, Cys379 and Tyr 380 on OGT. Our results show that shark single-domain antibodies targeting OGT can be used for in vitro detection and intracellular co-localization of OGT, providing a powerful tool for the study of OGT and O-GlcNAcylation."

Journal • OGA

Mechanistic Insights to the Binding of Antibody CR3022 Against RBD from SARS-CoV and HCoV-19/SARS-CoV-2: A Computational Study. (PubMed, Comb Chem High Throughput Screen) - "There were common conservative amino acids on the β2 sheet of RBD, including Tyr369, Phe377, Lys378, Tyr380, Gly381, Lys386, Leu390 and others. Therefore, the binding of CR3022 and HCoV19-RBD only draws on the partial mode of the binding of CR3022 and SARS-CoV-RBD, so there is a loss of affinity. Thus, in order to better fight the epidemic of COVID-19 with the CR3022 antibody, this antibody needs to further improve the neutralization efficiency of HCoV-19 through mutation of it's CDR region."

Journal • Infectious Disease • Novel Coronavirus Disease

4-Methylesculetin, a natural coumarin with intestinal anti-inflammatory activity, elicits a glutathione antioxidant response by different mechanisms. (PubMed, Chem Biol Interact) - "Molecular modelling calculation showed Lys70-B, Arg81-A, Glu381-B, Asp443-A, Ser444-A, Glu447-B and Ser475-A participated in electrostatic interaction, Lys70-B, Glu381-B and Arg81-A acted in the hydrophobic interactions and Trp73, Phe377 and Ala446 are responsible for the hydrogen bonds. Based on this, our results showed 4 ME acted by different mechanisms to control oxidative stress induced by intestinal damage, controlling the imbalance between myeloperoxidase activity and glutathione production, upregulating the glutathione S-transferase and glutathione reductase activities, preventing the Nrf2 and glutathione gene expression downregulation with consequent glutathione maintenance. Finally, 4 ME interacted at molecular level with glutathione reductase, stabilizing its enzymatic activity and reducing oxidative stress to take place in intestinal inflammatory process."

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