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.

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.