Effect of Egyptian spitting cobra Naja nubiae crude venom on immunogenic activity of rats.

Snakes show defensive activities, often counting visual or auditory displays against an aggressor. The study observed what happens to rats administered subcutaneously sub-lethal doses of crude venom Naja nubiae. The pro-inflammatory cytokines, such as tumor necrosis alpha (TNF-α) and interleukin-6 (IL-6), as well as the anti-inflammatory cytokines such as interleukin-10 (IL-10), and inflammatory mediator's prostaglandin E-2 (PG-E2), were evaluated. Vascular permeability (VP) was employed to assess how leaky or permeable blood vessels are in various tissues and organs, including the rat peritoneal cavity and lymphoid organs. Lymphoid organs' histological alterations brought on by Nubiae venom. The study found that the two venom doses-1/4 and 1/2 LD50-induced high levels of inflammatory activity as evidenced by the production of inflammatory cytokines. These findings demonstrated that venom enhanced innate immunity through specifically increased T helper cells, IL-6, TNF-α, IL-10, and PG-E2. The results reveal whether the venom has an immunomodulatory effect and promotes inflammation. The data have a substantial impact on the development of new drugs and treatments for inflammatory conditions.

Screening Stability, Thermochemistry, and Chemical Kinetics of 3-Hydroxybutanoic Acid as a Bifunctional Biodiesel Additive.

The thermo-kinetic aspects of 3-hydroxybutyric acid (3-HBA) pyrolysis in the gas phase were investigated using density functional theory (DFT), specifically the M06-2X theoretical level in conjunction with the cc-pVTZ basis set. The obtained data were compared with benchmark CBS-QB3 results. The degradation mechanism was divided into 16 pathways, comprising 6 complex fissions and 10 barrierless reactions. Energy profiles were calculated and supplemented with computations of rate coefficients and branching ratios over the temperature range of 600-1700 K at a pressure of 1 bar using transition state theory (TST) and Rice-Ramsperger-Kassel-Marcus (RRKM) methods. Thermodynamics results indicated the presence of six stable conformers within a 4 kcal mol-1 energy range. The estimated chemical kinetics results suggested that TST and RRKM approaches are comparable, providing confidence in our calculations. The branching ratio analysis reveals that the dehydration reaction pathway leading to the formation of H2O and CH3CH═CHCO2H dominates entirely at T ≤ 650 K. At these temperatures, there is a minor contribution from the simple homolytic bond fission reaction, yielding related radicals [CH3•CHOH + •CH2CO2H]. However, at T ≥ 700 K, this reaction becomes the primary decomposition route. At T = 1700 K, there is a minor involvement of a reaction pathway resulting in the formation of CH3CH(OH)•CH2 + •CHO(OH) with an approximate contribution of 16%, and a reaction leading to [•CH3 + •CH2OHCH2CO2H] with around 9%.

Identification of potential antiviral compounds from Egyptian sea stars against MERS-CoV with the in vitro and in silico experiments.

Recently, the world faced many epidemics which were caused by viral respiratory pathogens. Marine creatures including Asteroidea class have been one of the recent research topics due to their diverse and complex secondary metabolites. Some of these constituents exhibit antiviral activities. The present study aimed to extract and identify the potential antiviral compounds from Pentaceraster cumingi, Astropecten polyacanthus and Pentaceraster mammillatus. The results showed that promising activity of the methanolic extract of P. cumingi with 50% inhibitory concentration (IC50) of 3.21 mg/ml against MERS-CoV with a selective index (SI) of 13.975. The biochemical components of the extracts were identified by GC/MS analysis. The Molecular docking study highlighted the virtual mechanism of binding the identified compounds towards three PDB codes of MERS-CoV non-structural protein 10/16. Interestingly, 2-mono Linolein showed promising binding energy of -14.75 Kcal/mol with the second PDB code (5YNI) and -15.22 Kcal/mol with the third PDB code (5YNQ).

Computational analysis of substituent effects on proton affinity and gas-phase basicity of TEMPO derivatives and their hydrogen bonding interactions with water molecules.

The study investigates the molecular structure of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and its derivatives in the gas phase using B3LYP and M06-2X functional methods. Intermolecular interactions are analyzed using natural bond orbital (NBO) and atoms in molecules (AIM) techniques. NO2-substituted TEMPO displays high reactivity, less stability, and softer properties. The study reveals that the stability of TEMPO derivatives is mainly influenced by LP(e) → σ∗ electronic delocalization effects, with the highest stabilization observed on the oxygen atom of the nitroxide moiety. This work also considers electron density, atomic charges, and energetic and thermodynamic properties of the studied NO radicals, and their relative stability. The proton affinity and gas-phase basicity of the studied compounds were computed at T = 298 K for O-protonation and N-protonation, respectively. The studied DFT method calculations show that O-protonation is more stable than N-protonation, with an energy difference of 16.64-20.77 kcal/mol (22.80-25.68 kcal/mol) at the B3LYP (M06-2X) method. The AIM analysis reveals that the N-O…H interaction in H2O complexes has the most favorable hydrogen bond energy computed at bond critical points (3, - 1), and the planar configurations of TEMPO derivatives exhibit the highest EHB values. This indicates stronger hydrogen bonding interactions between the N-O group and water molecules.

Venomous gland transcriptome and venom proteomic analysis of the scorpion Androctonus amoreuxi reveal new peptides with anti-SARS-CoV-2 activity.

The recent COVID-19 pandemic shows the critical need for novel broad spectrum antiviral agents. Scorpion venoms are known to contain highly bioactive peptides, several of which have demonstrated strong antiviral activity against a range of viruses. We have generated the first annotated reference transcriptome for the Androctonus amoreuxi venom gland and used high performance liquid chromatography, transcriptome mining, circular dichroism and mass spectrometric analysis to purify and characterize twelve previously undescribed venom peptides. Selected peptides were tested for binding to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and inhibition of the spike RBD - human angiotensin-converting enzyme 2 (hACE2) interaction using surface plasmon resonance-based assays. Seven peptides showed dose-dependent inhibitory effects, albeit with IC50 in the high micromolar range (117-1202 µM). The most active peptide was synthesized using solid phase peptide synthesis and tested for its antiviral activity against SARS-CoV-2 (Lineage B.1.1.7). On exposure to the synthetic peptide of a human lung cell line infected with replication-competent SARS-CoV-2, we observed an IC50 of 200 nM, which was nearly 600-fold lower than that observed in the RBD - hACE2 binding inhibition assay. Our results show that scorpion venom peptides can inhibit the SARS-CoV-2 replication although unlikely through inhibition of spike RBD - hACE2 interaction as the primary mode of action. Scorpion venom peptides represent excellent scaffolds for design of novel anti-SARS-CoV-2 constrained peptides. Future studies should fully explore their antiviral mode of action as well as the structural dynamics of inhibition of target virus-host interactions.

Conus vexillum venom induces oxidative stress in Ehrlich's ascites carcinoma cells: an insight into the mechanism of induction

Background: It is estimated that venoms of marine cone snails (genus Conus) contain more than 100,000 different small peptides with a wide range of pharmacological and biological actions. Some of these peptides were developed into potential therapeutic agents and as molecular tools to understand biological functions of nervous and cardiovascular systems. In this study we examined the cytotoxic and anticancer properties of the marine vermivorous cone snail Conus vexillum (collected from Hurgada and Sharm El-Shaikh, Red Sea, Egypt) and suggest the possible mechanisms involved. The in vitro cytotoxic effects of Conus venom were assessed against Ehrlich's ascites carcinoma (EAC) cells. Results: Conus venom treatment resulted in concentration-dependent cytotoxicity as indicated by a lactate dehydrogenase leakage assay. Apoptotic effects were measured in vivo by measuring levels of reactive oxygen species and oxidative defense agents in albino mice injected with EAC cells. Conus venom (1.25 mg/kg) induced a significant increase (p < 0.05) in several oxidative stress biomarkers (lipid peroxidation, protein carbonyl content and reactive nitrogen intermediates) of EAC cells after 3, 6, 9 and 12 hours of venom injection. Conus venom significantly reduced (p < 0.05) the activities of oxidative defense enzymes (catalase and superoxide dismutase) as well as the total antioxidant capacity of EAC cells, as evidenced by lowered levels of reduced glutathione. Conclusions: These results demonstrate the cytotoxic potential of C. vexillum venom by inducing oxidative stress mediated mechanisms in tumor cells and suggest that the venom contains novel molecules with potential anticancer activity.(AU)

Conus vexillum venom induces oxidative stress in Ehrlich's ascites carcinoma cells: an insight into the mechanism of induction

It is estimated that venoms of marine cone snails (genus Conus) contain more than 100,000 different small peptides with a wide range of pharmacological and biological actions. Some of these peptides were developed into potential therapeutic agents and as molecular tools to understand biological functions of nervous and cardiovascular systems. In this study we examined the cytotoxic and anticancer properties of the marine vermivorous cone snail Conus vexillum (collected from Hurgada and Sharm El-Shaikh, Red Sea, Egypt) and suggest the possible mechanisms involved. The in vitro cytotoxic effects of Conus venom were assessed against Ehrlich’s ascites carcinoma (EAC) cells. Results Conus venom treatment resulted in concentration-dependent cytotoxicity as indicated by a lactate dehydrogenase leakage assay. Apoptotic effects were measured in vivo by measuring levels of reactive oxygen species and oxidative defense agents in albino mice injected with EAC cells. Conus venom (1.25 mg/kg) induced a significant increase ( p  < 0.05) in several oxidative stress biomarkers (lipid peroxidation, protein carbonyl content and reactive nitrogen intermediates) of EAC cells after 3, 6, 9 and 12 hours of venom injection. Conus venom significantly reduced ( p  < 0.05) the activities of oxidative defense enzymes (catalase and superoxide dismutase) as well as the total antioxidant capacity of EAC cells, as evidenced by lowered levels of reduced glutathione.Conclusions These results demonstrate the cytotoxic potential of C. vexillum venom by inducing oxidative stress mediated mechanisms in tumor cells and suggest that the venom contains novel.