Background: Severe acute respiratory syndrome (SARS) has been initiating pandemics since the beginning of the century. In December 2019, the world was hit again by a devastating SARS episode that has so far infected almost four million individuals worldwide, with over 200,000 fatalities having already occurred by mid-April 2020, and the infection rate continues to grow exponentially. SARS coronavirus 2 (SARS-CoV-2) is a single stranded RNA pathogen which is characterised by a high mutation rate. It is vital to explore the mutagenic capability of the viral genome that enables SARS-CoV-2 to rapidly jump from one host immunity to another and adapt to the genetic pool of local populations.

Methods: For this study, we analysed 2301 complete viral sequences reported from SARS-CoV-2 infected patients. SARS-CoV-2 host genomes were collected from The Global Initiative on Sharing All Influenza Data (GISAID) database containing 9 genomes from pangolin-CoV origin and 3 genomes from bat-CoV origin, Wuhan SARS-CoV2 reference genome was collected from GeneBank database. The Multiple sequence alignment tool, Clustal Omega was used for genomic sequence alignment. The viral replicating enzyme, 3-chymotrypsin-like cysteine protease (3CL^pro) that plays a key role in its pathogenicity was used to assess its affinity with pharmacological inhibitors and repurposed drugs such as anti-viral flavones, biflavanoids, anti-malarial drugs and vitamin supplements.

Results: Our results demonstrate that bat-CoV shares>96% similar identity, while pangolin-CoV shares 85.98% identity with Wuhan SARS-CoV-2 genome. This in-depth analysis has identified 12 novel recurrent mutations in South American and African viral genomes out of which 3 were unique in South America, 4 unique in Africa and 5 were present in-patient isolates from both populations. Using state of the art in silico approaches, this study further investigates the interaction of repurposed drugs with the SARS-CoV-2 3CL^pro enzyme, which regulates viral replication machinery

Conclusions: Overall, this study provides insights into the evolving mutations, with implications to understand viral pathogenicity and possible new strategies for repurposing compounds to combat the nCovid-19 pandemic.

Juncao grass (Cenchrus fungigraminus Z.X. Lin, D.M. Lin, and S.R. Lan) is a recently developed C4 forage which has been introduced to several tropical countries supported by different aid programs. However, there is no information on the potential of forage production, nutritive value, and agronomic characteristics of this new species to support management recommendations. This research aimed to compare two cultivars of Juncao to Guatemala (Tripsacum andersonii J.R. Gray) and Elephant grass [Cenchrus purpureus (Schumach.) Morrone cv. Napier] in relation to annual forage production and nutritive value subjected to different pre-harvest canopy heights. The trial was designed using randomised blocks (n = 3) in a split-plot arrangement where pre-harvesting canopy heights (0.5, 1.0, 1.5, and 2.0 m) composed the main plots and forage species/cultivars (n = 4) as the subplots. The annual forage accumulation of Juncao green and purple was approximately double that of Elephant and Guatemala grass when averaged across 2 years, while crude protein and metabolisable energy concentration was similar to Elephant and higher than Guatemala grass. Juncao green and purple cultivars should be harvested between 1 and 2 m of pre-harvest canopy height, with shorter pre-harvest targets favouring nutritional value and taller targets promoting greater biomass production per harvest, although no increments in annual forage accumulation were observed when pre-harvesting canopy height was over 1 m. The high forage production of Juncao grass, combined with its nutritional value comparable to other tropical forage, indicates substantial potential for its adoption in cut-and-carry systems in the wet tropics.

The caveolin (Cav) family of proteins comprises key constituents of caveolar structures in cell membranes, which are involved in receptor-independent endocytosis and cellular signalling pathways. Three isoforms of caveolin viz. cav-1, cav-2 and cav-3 encoded by CAV1, CAV2 and CAV3 genes respectively, have been reported to be expressed in various tissues. Genetic polymorphism in CAV has been identified as associated with the development of pathological changes in the cardiovascular system, chronic kidney disease as well as neurodegenerative diseases of the brain and retina such as Alzheimer's disease, Parkinson's disease and glaucoma. In this study, we investigate and characterise various polymorphisms associated with CAV1, CAV2 and CAV3 by using a combination of in silico algorithms such as SIFT, Polyphen 2.0, I-Mutant, PROVEAN, PANTHER, SNP&Go, PhD-SNP, MutPred and SNPEffects. Three-dimensional comparative modelling was performed using Phyre2 server, ab initio modelling, using the I-TASSER and RaptorX program. The predicted models were evaluated using Ramachandran plot to establish the accuracy of the models generated. The resulting mutant and wild type proteins obtained were energy minimized in Swiss Deep Viewer and evaluated. The study has identified two of the non-synonymous single nucleotide polymorphism (nsSNP) in CAV3 gene that may have a damaging effect on the protein stability. The surface residues in the wild type and mutant forms highlight different accessible surface area (ASA) of amino acid residues in the corresponding proteins. Our analysis predicted that none of the known nsSNPs have a negative effect on the CAV1 and CAV2 protein structures. Phylogenetic analysis using ConSurf further identified that most of the disease-associated nsSNPs were within the conserved regions in human cav3.

Background: Retinal ganglion cell (RGC) degeneration is a major feature of glaucoma pathology. Neuroprotective approaches that delay or halt the progression of RGC loss are needed to prevent vision loss which can occur even after conventional medical or surgical treatments to lower intraocular pressure.

Objective: The aim of this review was to examine the progress in genetics and cellular mechanisms associated with endoplasmic reticulum (ER) stress, RGC dysfunction and cell death pathways in glaucoma.

Materials and Methods: Here, we review the involvement of neurotrophins like brain derived neurotrophic factor (BDNF) and its high affinity receptor tropomyosin receptor kinase (TrkB) in glaucoma. The role of ER stress markers in human and animal retinas in health and disease conditions is also discussed. Further, we analysed the literature highlighting genetic linkage in the context of primary open angle glaucoma and suggested mechanistic insights into potential therapeutic options relevant to glaucoma management.

Results: The literature review of the neurobiology underlying neurotrophin pathways, ER stress and gene associations provide critical insights into association of RGCs death in glaucoma. Alteration in signalling pathway is associated with increased risk of misfolded protein aggregation in ER promoting RGC apoptosis. Several genes that are linked with neurotrophin signalling pathways have been reported to be associated with glaucoma pathology.

Conclusion: Understanding genetic heterogeneity and involvement of neurotrophin biology in glaucoma could help to understand the complex pathophysiology of glaucoma. Identification of novel molecular targets will be critical for drug development and provide neuroprotection to the RGCs and optic nerve.