Peptide modelling and screening against human ACE2 and spike glycoprotein RBD of SARS-CoV-2.

Outbreak of Coronavirus Disease 2019 (COVID-19) has become a great challenge for scientific community globally. Virus enters cell through spike glycoprotein fusion with ACE2 (Angiotensin-Converting Enzyme 2) human receptor. Hence, spike glycoprotein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a potential target for diagnostics, vaccines, and antibodies. Also, virus entry can be prevented by blocking ACE2 thus, ACE2 can be considered potential target for therapeutics. As being highly specific, safe and efficacious, peptides hold their place in therapeutics. In present study, we retrieved sequence of 70 peptides from Antiviral Peptide Database (AVPdb), modelled them using 3D structure predicting web tool and docked them with receptor binding domain (RBD) of spike protein and human host receptor ACE2 using peptide-protein docking. It was observed that peptides have more affinity towards ACE2 in comparison with spike RBD. Interestingly it was noticed that most of the peptides bind to RBM (residue binding motif) which is responsible for ACE2 binding at the interface of RBD while, for ACE2, peptides prefer to bind the core cavity rather than RBD binding interface. To further investigate how peptides at the interface of RBD or ACE2 alter the binding between RBD and ACE2, protein-protein docking of RBD and ACE2 with and without peptides was performed. Peptides, AVP0671 at RBD and AVP1244 at ACE2 interfaces significantly reduce the binding affinity and change the orientation of RBD and ACE2 binding. This finding suggests that peptides can be used as a drug to inhibit virus entry in cells to stop COVID-19 pandemic in the future after experimental evidences.

Bayesian QTL analyses using pedigreed families of an outcrossing species, with application to fruit firmness in apple.

KEY MESSAGE: Proof of concept of Bayesian integrated QTL analyses across pedigree-related families from breeding programs of an outbreeding species. Results include QTL confidence intervals, individuals' genotype probabilities and genomic breeding values. Bayesian QTL linkage mapping approaches offer the flexibility to study multiple full sib families with known pedigrees simultaneously. Such a joint analysis increases the probability of detecting these quantitative trait loci (QTL) and provide insight of the magnitude of QTL across different genetic backgrounds. Here, we present an improved Bayesian multi-QTL pedigree-based approach on an outcrossing species using progenies with different (complex) genetic relationships. Different modeling assumptions were studied in the QTL analyses, i.e., the a priori expected number of QTL varied and polygenic effects were considered. The inferences include number of QTL, additive QTL effect sizes and supporting credible intervals, posterior probabilities of QTL genotypes for all individuals in the dataset, and QTL-based as well as genome-wide breeding values. All these features have been implemented in the FlexQTL(™) software. We analyzed fruit firmness in a large apple dataset that comprised 1,347 individuals forming 27 full sib families and their known ancestral pedigrees, with genotypes for 87 SSR markers on 17 chromosomes. We report strong or positive evidence for 14 QTL for fruit firmness on eight chromosomes, validating our approach as several of these QTL were reported previously, though dispersed over a series of studies based on single mapping populations. Interpretation of linked QTL was possible via individuals' QTL genotypes. The correlation between the genomic breeding values and phenotypes was on average 90 %, but varied with the number of detected QTL in a family. The detailed posterior knowledge on QTL of potential parents is critical for the efficiency of marker-assisted breeding.

Environmental genotoxicity and cancer risk in humans: a combined evaluation correlating the results of the Tradescantia micronucleus assay in the field and human biomarker assessments in serum. I. The TRAD-MCN assay.

It is well documented that environmental pollution from industrial activity, sewage farms, hazardous waste sites, incinerators, etc, contributes to the overall cancer risk and that this contribution can be considerable under certain circumstances. It is important, therefore, to identify the level of genotoxic activity in the environment and to relate it to biomarkers of cancer risk in humans. After reviewing a range of cytogenetic assays, we have selected the Tradescantia micronucleus assay (TRAD-MCN) developed by Ma et al to be used in indoor and field evaluations. The meiotic pollen mother cells of T clone 4430 are particularly sensitive to chemical pollutants; the buds are exposed for 6-8 h. We describe assays made down wind from a coal-fired power station and from the vicinity of two waste sites. Statistically significant results were obtained at 200 m and 600 m down wind from the power station; higher levels of micronucleus frequencies (MN) were found in foggy rather than dry conditions. Similarly, in the vicinity of two waste sites the MN frequencies were significantly increased in both dry and foggy conditions up to 1.5 km down wind; this was despite previous efforts to rehabilitate the sites. The TRAD-MCN assay is sensitive, reproducible, easy to perform, well standardized, inexpensive and undemanding in equipment. We propose that it be the primary test for genotoxicity evaluation and mapping followed, in suspicious areas, by human biomarker assays.