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.

Sequential Antioxidants Foliar Application Can Alleviate Negative Consequences of Salinity Stress in Vicia faba L.

Salinity is one of the most limiting abiotic stresses in agricultural productivity. Exogenously applied antioxidants successfully enabled salt-stressed plants to cope with stress. Two-season field experiments were conducted consecutively in 2016/17 and 2017/18 to study the effects of foliar applications of singular (ascorbate, AsA; proline, Pro; and glutathione, GSH) or sequential (AsA-Pro-GSH and GSH-Pro-AsA) antioxidants on growth, yield, physio-biochemical attributes, and enzymatic and non-enzymatic antioxidative defense system of Vicia faba L. (CV. Sakha-1) plants grown under saline soil conditions (EC = 4.53 dS m-1). Under soil salinity conditions, AsA, Pro, or GSH-Pro-ASA improved growth and productivity, photosynthesis efficiency, stomatal conductance (gs), plant water status, as well as enzymatic and non-enzymatic antioxidants. However, sequential AsA-Pro-GSH foliar application followed by singular GSH significantly exceeded all other treatments (i.e., AsA, Pro, and GSH-Pro-AsA), improving growth characteristics (shoot length, shoot fresh and dry weights, and leaves area), photosynthesis efficiency, stomatal conductance, plant water status, and yield and its components (green pods weight/plant-1, green pods yield/hectare-1, and seed yield/hectare-1), as well as enzymatic (ascorbate peroxidase, catalase, superoxide dismutase, and glutathione reductase) and non-enzymatic (AsA, GSH, Pro, phenolic aglycone, phenolic glycosides) antioxidants compared to control. Overall, our results clearly demonstrate that sequential AsA-Pro-GSH foliar application has a positive effect on salt-stressed Vicia faba plants.

Shelf life extension of wheat bread by alhydwan flour and Carboxymethylcellulose and improvement of their quality characteristics, dough rheological and microstructure.

Alhydwan, has been used in bakery products for many years in South of Yemen. Alhydwan primary function in bakery products is to inhibit moisture content during storage, leading to improved shelf life. However, as a fresh strategy to bread staling, no extensive study has been conducted to evaluate its potential. The present study therefore examined the alhydwan as a comparison with Carboxymethylcellulose (CMC) at 0.5% (w/w) level in dough rheology improvement, microstructure, quality parameters and delayed wheat bread staling. The CMC or alhydwan for farinograph characteristics comprising the dough's portrayed showed greater water absorption, while growth and stability time was significantly decreased. Staling of bread, the findings showed that in both alhydwan and CMC minimized crumb hardening frequency and enhanced freshness, quality and retention ability for moisture, making the bread softer and postponed staling. The microstructure of CMC or alhydwan supplemented formulation showed the distinguishable characteristics and constituents that could explain, to some degree, that the CMC and alhydwan had antistaling effect. The incorporation of alhydwan such as CMC into the formulation of bread could thus play a sustainable role in improving the quality of bread by having an extended shelf life.

A Comprehensive Analysis of cis-Acting RNA Elements in the SARS-CoV-2 Genome by a Bioinformatics Approach.

The emergence of a new coronavirus (CoV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for severe respiratory disease in humans termed coronavirus disease of 2019 (COVID-19), became a new global threat for health and the economy. The SARS-CoV-2 genome is about a 29,800-nucleotide-long plus-strand RNA that can form functionally important secondary and higher-order structures called cis-acting RNA elements. These elements can interact with viral proteins, host proteins, or other RNAs and be involved in regulating translation and replication processes of the viral genome and encapsidation of the virus. However, the cis-acting RNA elements and their biological roles in SARS-CoV-2 as well as their comparative analysis in the closely related viral genome have not been well explored, which is very important to understand the molecular mechanism of viral infection and pathogenies. In this study, we used a bioinformatics approach to identify the cis-acting RNA elements in the SARS-CoV-2 genome. Initially, we aligned the full genomic sequence of six different CoVs, and a phylogenetic analysis was performed to understand their evolutionary relationship. Next, we predicted the cis-acting RNA elements in the SARS-CoV-2 genome using the structRNAfinder tool. Then, we annotated the location of these cis-acting RNA elements in different genomic regions of SARS-CoV-2. After that, we analyzed the sequence conservation patterns of each cis-acting RNA element among the six CoVs. Finally, the presence of cis-acting RNA elements across different CoV genomes and their comparative analysis was performed. Our study identified 12 important cis-acting RNA elements in the SARS-CoV-2 genome; among them, Corona_FSE, Corona_pk3, and s2m are highly conserved across most of the studied CoVs, and Thr_leader, MAT2A_D, and MS2 are uniquely present in SARS-CoV-2. These RNA structure elements can be involved in viral translation, replication, and encapsidation and, therefore, can be potential targets for better treatment of COVID-19. It is imperative to further characterize these cis-acting RNA elements experimentally for a better mechanistic understanding of SARS-CoV-2 infection and therapeutic intervention.

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.