Edited by Jesus Avila Keywords:Tau protein (4R/1N) Microtubule protein Homocysteine thiolactone N-Homocysteinylation a b s t r a c t Tau isoforms promote neuronal integrity through binding and stabilization of microtubule proteins (MTP). It has been shown that hyperphosphorylation of tau contributes to Alzheimer's disease (AD) pathology and related tauopathies. However, other pathogenic modifications of tau have not been well characterized. It is well accepted that elevated level of homocysteine (Hcy) is associated with neurodegenerative diseases such as AD. As a result of N-homocysteinylation of lysine residues, Hcy becomes a component of proteins, as a protein-homocystamide adduct, which affects protein structure and function. Here we demonstrate that N-homocysteinylation of human tau (4R/1N isoform) inhibits its function via impaired tau-tubulin specific binding and MTP assembly dynamics in vitro.

Despite using effective drugs and vaccines for Covid 19, due to some limitations of current strategies and the high rate of coronavirus mutation, the development of medicines with effective inhibitory activity against this infection is essential. The SARS-CoV-2 enters the cell by attaching its receptor-binding domain (RBD) of Spike to angiotensin-converting enzyme-2 (ACE2). According to previous studies, the natural peptide Urtica dioica agglutinin (UDA) exhibited an antiviral effect on SARS-CoV, but its mechanism has not precisely been elucidated. Here, we studied the interaction between UDA and RBD of Spike protein of SARS-CoV-2. So, protein-protein docking of RBD-UDA was performed using Cluspro 2.0. To further confirm the stability of the complex, the RBD-UDA docked complex with higher binding affinity was studied using Molecular Dynamic simulation (via Gromacs 2020.2), and MM-PBSA calculated the binding free energy of the system. In addition, ELISA assay was used to examine the binding of UDA with RBD protein. Results were compared to ELISA of RBD-bound samples of convalescent serum IgG (from donors who recovered from Covid 19). Finally, the toxicity of UDA is assessed by using MTT assay. The docking results show UDA binds to the RBD binding site. MD simulation illustrates the UDA-RBD complex is stable during 100 ns of simulation, and the average binding energy was calculated to be -47.505 kJ/mol. ELISA and, MTT results show that UDA binds to RBD like IgG-RBD binding and may be safe in human cells. Data presented here indicate UDA interaction with S-protein inhibits the binding sites of RBD, it can prevent the virus from attaching to ACE2 and entering the host cell.

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In the present study, organophosphorus hydrolase enzyme on Functionalized ferric magnetic nanoparticles was immobilized by the covalent binding method. The Optimized amount for parameters of mg EDAC/mg nanoparticles, enzyme units (U)/mg nanoparticles, reaction time, and pH were determined to be 6.125, 0.1341, 3 h and 6.15 respectively. The amount of immobilization yield according to the enzyme activity was obtained to be 70% and also the amount of immobilized enzyme on nanoparticles was 0.25 U/mg nanoparticles. Stability studies showed significant increase in immobilized enzyme stability at 4, 25 and 45°C. The stability of Immobilized enzyme showed a 6.3-fold increase in comparison to free enzyme at 4°C. The results demonstrated that the pH stability of the immobilized enzyme significantly increased in comparison with free enzyme. The immobilized enzyme was usable and recoverable for seven cycles. The results depicted that 80% of enzyme activity was retained after fifth cycle. FTIR test showed the covalent binding of enzyme to magnetic nanoparticles’ surface and the modified enzyme magnetic nanoparticles property was superparamagnetic by vibrating sample magnetometer test.