Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

BackgroundAntibacterial, immunomodulatory and antioxidant properties of aerial parts of Barleria lupulina Lindl were investigated in the present communication.MethodsThe antibacterial, antioxidant and immunomodulatory properties of B. lupulina (methanol soluble leaf and stem extracts) was analyzed by minimum inhibitory concentration, total phenolic contents, DPPH radical scavenging activity, determination of toxicity, hemagglutination antibody titre, delayed type hypersensitivity and neutrophil adhesion test, respectively.ResultsMethanol soluble leaf extract (MLE) contains more soluble bioactive compounds inhibiting the growth of five bacterial pathogens viz., Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Salmonella typhi even at MICs of 1.25 and 2.5 mg/mL. Aqueous stem extract (ASE) was least effective while MLE was highly effective in inhibiting the growth and survival of bacterial pathogens. While testing the effect of these extracts in animal model, no mortality of albino rats was recorded by using MLE and MSE at the concentrations from 200 to 600 mg/kg of their body weight. The MLE showed significant result in agglutination reaction and induced paw edema volumes when compared with untreated group (control). Both MLE and MSE extracts significantly increased neutrophil adhesion with increase in doses of extracts. MLE was found to have more potent immune-stimulant properties than the MSE. High phenolic contents were found in MSE while lowest IC50 values were found in MLE in term of DPPH radical scavenging activity.ConclusionsMethanol soluble leaf and stem extract of Barleria lupulina contains antibacterial, antioxidants and immunomodulating phytochemical compounds that was effective for antibacterial, antioxidant and immunomodulatory properties. These may be used as synthetic drug.

Both human and animals, for their nutritional requirements, mainly rely on the plant-based foods, which provide a wide range of nutrients. Minerals, proteins, vitamins are among the nutrients which are essential and need to be available in adequate amount in edible portion of the staple crops. Increasing nutritional content in staple crops either through agronomic biofortification or through conventional plant-breeding strategies continue to be a huge task for scientists around the globe. Although some success has been achieved in recent past, in most cases, we have fallen short of expected targets. To maximize the nutrient uptake and partitioning to different economic part of plants, scientists have employed and tailored several biofortification strategies. But in present agricultural and environmental concerns, these approaches are not much effective. Henceforth, we are highlighting the recent developments and promising aspects of microbial-assisted and genomic-assisted breeding as candidate biofortification approach, that have contributed significantly in increasing nutritional content in grains of different crops. The methods used to date to accomplish nutrient enrichment with recently emerging strategies that we believe could be the most promising and holistic approach for future biofortification program. Results are encouraging, but for future perspective, the existing knowledge about the strategies needs to be confined. Concerted scientific investment are required to widen up these biofortification strategies, so that it could play an important role in ensuring nutritional security of ever-growing population in growing agricultural and environmental constraints.

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