Preprocesamiento de los fármacos antivirales candidatos contra COVID-19 en modelos de SARS cov2. Objetivos / Preprocessing of the candidate antiviral drugs against COVID-19 in models of SARS cov2 targets

Although many viral infections are self-limiting, other are real health challenges like COVID-19 since many viruses possess just few drug gable targets to be treated with small drug molecules. Corona virus genome encodes for up to 17 main proteins. Orf1ab encodes for polyprotein. COVID-19 structural proteins are the spike S, membrane M, envelope E and the nucleocapsid N protein while other are non-structural proteins designated as NSP1-13 for non-structural proteins. Among NSP the most important corona virus targets for developing antiviral drugs are the papain-like protease, PDB ID: 6m03 and RNA polymerase NSP12, PDB ID: 6nur. NCBI, NIH Genbank, Uniprot, PDB, DrugBank, ChemSpider databases and bioinformatics editor softwares like ICM Mol soft pro and Swiss Dock were used in addition to the in vitro lab model of viral protease were integrated to retrieve and analyze corona virus targets and to select the candidate ligands in an attempt to evaluate the inhibitory efficacy of different experimental and approved drugs which were further optimized and searched for the highly similar approved drug. This step aims to adopt drug repurposing to speed the development of antiviral drugs and recommend rational in vivo and clinical studies. After COVID-19 targets had been analyzed the drugs that shared > 70% similarity to the binding sites of those targets were reversin, pentagastrin, remdesivir, norfloxacin and nitazoxanide against COVID-19 papain-like protease whereas benzyl glutathione, lopinavir and hydroxymethylglutathione against RNA polymerase. The anti-resistance reversin showed the highest inhibitory efficacy against COVID-19 papain-like protease as indicated by the ligand-protease binding energy with Mol soft pro analysis. The calculated inhibitory binding was -137.30 kJ/mol z > 1.9 as compared with the tetrazapentadecanoate -129.57 kJ/mol z = 4.0, whereas remdesivir, pentagastrin, nitazoxanide and norfloxacin had a moderate antiprotease activity (>- 100 kJ/mol). Norfloxacin shoresults showed a slight consistency between in vitro and in silico models. Although benzyl glutathione is an experimental compound, however it had the highest RNA polymerase inhibiting efficacy with -129 kJ/mol binding energy which is even higher than lopinavir and Favinavir. From the overall results, reversin, oligopeptides, quinolones and antiviral drugs may widen the treatment options for COVID-19 if further evaluated in clinical studies

Combinación de bardoxolona y DMF Mejora la isquemia cerebral/reperfusión Lesión en ratas macho / Combination of Bardoxolone and DMF Ameliorates Cerebral Ischemia / Reperfusion Injury in Male Rats

Background: Ischemic stroke has been ranked as the second cause of death in patients worldwide. Inflammation which is activated during cerebral ischemia/reperfusion (I/R) is an important mechanism leading to brain injury. The present study aimed to investigate the effect of Berberine on cerebral I/R injury and the role of inflammation in this process. Material and Methods: The study was carried out on 36 Wistar-albino rats, divided into four groups including: Sham group, I/R group, I/R+ (control-vehicle DMSO) and I/R+ Berberine 5 mg/kg injected intraperitoneally 1 hour before induction of ischemia. Measurement of brain tissue IL-1ß, ICAM1, caspase-3, Notch 1 and Jagged 1 was done after one hour of reperfusion in addition to assessment of the brain infracted area and histopathological analysis. Results: Berberine attenuates cerebral I/R injury induced increase in inflammatory cytokine (IL-1ß), adhesion molecule (ICAM-1) and proapoptotic enzyme (caspase-3). Additionally, it reduces the size of infracted area and histopathological damage; such protective effect could be mediated by Notch 1 signaling pathway since Berberine further unregulated the increased levels of Notch 1 and Jagged 1 seen in brain with I/R injury. Conclusions: Berberine has a neurocytoprotective outcome against cerebral I/R injury which is manifested as anti-inflammatory anti-apoptotic effect that preserved cell structure and viability, in the meantime this effect could be mediated by Notch 1 signaling pathway.

Improve Markers of Oxidative Stress and Coagulation Parameters in Response to Atorvastatin Therapy.

Aims: This study was undertaken to investigate the antioxidant effects of atorvastatin in treating cases of atherosclerosis associated with hyperlipidemia. Methodology: Forty local domestic rabbits were assigned to five groups (eight rabbits in each group): After two weeks acclimatization period, a group of 8 rabbits (Group I) were used as the baseline values of the study parameters. Another 8 rabbits were selected and maintained on standard chow diet (4% fat, 18% protein, 60% carbohydrate, and 4% fibers) throughout the experiment (12 weeks) and served as a normal diet control (Group II). The rest 24 rabbits were fed on an atherogenic diet for 8 weeks to induce atherogenesis. At the end of 8th week, a group of 8 atherogenic rabbits (Group III) were separated and sacrificed and served as an atherogenic-baseline group. The remaining 16 atherogenic rabbits were randomly allocated into two groups; first group received atherogenic diet only for the next four weeks and served as an atherogenic control (Group IV). The other group received atorvastatin (Group V). Results: Blood samples were collected for serum lipids, coagulation parameters and oxidation parameters. Results showed a significant improvement in the coagulation parameters and oxidation parameters in the atorvastatin treated group compared to the atherogenic control group (P= .01). Conclusion: This study illustrated the beneficial anti-oxidant effects of atorvastatin in treating atherosclerosis associated with hyperlipidemia.