A Computational Approach Identified Andrographolide as a Potential Drug for Suppressing COVID-19-Induced Cytokine Storm.

BACKGROUND: The newly identified betacoronavirus SARS-CoV-2 is the causative pathogen of the coronavirus disease of 2019 (COVID-19) that killed more than 3.5 million people till now. The cytokine storm induced in severe COVID-19 patients causes hyper-inflammation, is the primary reason for respiratory and multi-organ failure and fatality. This work uses a rational computational strategy to identify the existing drug molecules to target host pathways to reduce the cytokine storm. RESULTS: We used a "host response signature network" consist of 36 genes induced by SARS-CoV-2 infection and associated with cytokine storm. In order to attenuate the cytokine storm, potential drug molecules were searched against "host response signature network". Our study identified that drug molecule andrographolide, naturally present in a medicinal plant Andrographis paniculata, has the potential to bind with crucial proteins to block the TNF-induced NFkB1 signaling pathway responsible for cytokine storm in COVID-19 patients. The molecular docking method showed the binding of andrographolide with TNF and covalent binding with NFkB1 proteins of the TNF signaling pathway. CONCLUSION: We used a rational computational approach to repurpose existing drugs targeting host immunomodulating pathways. Our study suggests that andrographolide could bind with TNF and NFkB1 proteins, block TNF-induced cytokine storm in COVID-19 patients, and warrant further experimental validation.

Silicon and its application method effects on modulation of cadmium stress responses in Triticum aestivum (L.) through improving the antioxidative defense system and polyamine gene expression.

Identification of the optimum application method of exogenous supports for crop plants to improve their growth under environmental stresses such as heavy metals represents key priorities for researchers worldwide. Influences of different application methods of silicon (Si; 3 mM); soil treatment, foliar spray and seed soaking on growth, chlorophyll fluorescence, photosynthetic gas exchange, cell membrane injury, osmoprotectants contents, antioxidative defense system activity, and polyamines contents and their gene expression in wheat plants grown under normal and 2 mM cadmium (Cd) stress conditions were investigated in 3-repeated pot experiment. Cd stress severely depressed growth, chlorophyll fluorescence, photosynthetic gas exchange, tissue health, water use efficiency (WUE) and Si content, and elevated osmoprotectants and Cd2+ contents, antioxidative defense system activity, and polyamines contents and their gene expression. However, Si in different application methods alleviated the Cd stress effects and significantly reduced Cd2+ and MDA contents and electrolyte leakage, significantly increased growth, chlorophyll fluorescence, photosynthetic gas exchange, WUE, membrane stability index, relative water content and Si content, and further increased proline and soluble sugars contents, antioxidative (enzymatic and non-enzymatic) defense system activity, and polyamines contents and their gene expression. Among the three methods, Si applied as soil addition was the best and most effective in alleviating the Cd stress effects.

A novel Moringa oleifera leaf extract can mitigate the stress effects of salinity and cadmium in bean (Phaseolus vulgaris L.) plants.

Phaseolus vulgaris plants were grown in the presence of NaCl and/or CdCl2 beginning from the second week, sprayed twice with moringa leaf extract (MLE) at 21 and 28 days after sowing (DAS), and were sampled at 35 DAS for growth and chemical analyses and yielded at the end of experiment. Growth traits, level of photosynthetic pigments, green pod yield and pod protein were significantly reduced with exposing the plants to NaCl and/or CdCl2. However, the follow up foliar application with MLE detoxified the stress generated by NaCl and/or CdCl2 and significantly enhanced the aforementioned parameters. Either individual or combined used stresses increased the electrolyte leakage (EL), lipid peroxidation and plant Cd(2+) content, and decreased the membrane stability index (MSI) and relative water content (RWC). However, the foliar application of MLE in the absence of the stress improved the MSI and RWC and minimized plant Cd(2+) content but could not affect EL and lipid peroxidation. Proline content and the activity of antioxidant enzymes showed a significant increase in response to MLE as well as to NaCl and/or CdCl2 stress.