Potential of artificial intelligence to accelerate diagnosis and drug discovery for COVID-19.

The coronavirus disease (COVID-19) pandemic has caused havoc worldwide. The tests currently used to diagnose COVID-19 are based on real time reverse transcription polymerase chain reaction (RT-PCR), computed tomography medical imaging techniques and immunoassays. It takes 2 days to obtain results from the RT-PCR test and also shortage of test kits creating a requirement for alternate and rapid methods to accurately diagnose COVID-19. Application of artificial intelligence technologies such as the Internet of Things, machine learning tools and big data analysis to COVID-19 diagnosis could yield rapid and accurate results. The neural networks and machine learning tools can also be used to develop potential drug molecules. Pharmaceutical companies face challenges linked to the costs of drug molecules, research and development efforts, reduced efficiency of drugs, safety concerns and the conduct of clinical trials. In this review, relevant features of artificial intelligence and their potential applications in COVID-19 diagnosis and drug development are highlighted.

An immunoinformatics approach for the design of a multi-epitope vaccine targeting super antigen TSST-1 of Staphylococcus aureus.

BACKGROUND: TSST-1 is a secretory and pyrogenic superantigen that is being responsible for staphylococcal mediated food poisoning and associated clinical manifestations. It is one of the main targets for the construction of vaccine candidates against Staphylococcus aureus. Most of the vaccines have met failure due to adverse reactions and toxicity reported during late clinical studies. To overcome this, an immunoinformatics approach is being used in the present study for the design of a multi-epitope vaccine to circumvent the problems related to toxicity and allergenicity. RESULTS: In this study, a multi-epitope vaccine against Staphylococcus aureus targeting TSST-1 was designed through an immunoinformatics approach. B cell and T cell epitopes were predicted in silico and mapped with linkers to avoid junctional immunogenicity and to ensure the efficient presentation of exposed epitopes through HLA. ß-defensin and PADRE were adjusted at the N-terminal end of the final vaccine as adjuvants. Physiochemical parameters, antigenicity, and allergenicity of the vaccine construct were determined with the help of online servers. The three-dimensional structure of the vaccine protein was predicted and validated with various tools. The affinity of the vaccine with TLR-3 was studied through molecular docking studies and the interactions of two proteins were visualized using LigPlot+. The vaccine was successfully cloned in silico into pET-28a (+) for efficient expression in E. coli K12 system. Population coverage analysis had shown that the vaccine construct can cover 83.15% of the global population. Immune simulation studies showed an increase in the antibody levels, IL-2, IFN-γ, TGF-ß, B cell, and T cell populations and induced primary, secondary, and tertiary immune responses. CONCLUSION: Multi-epitope vaccine designed through a computational approach is a non-allergic and non-toxic antigen. Preliminary in silico reports have shown that this vaccine could elicit both B cell and T cell responses in the host as desired.

Application of IgY antibodies against staphylococcal protein A (SpA) of Staphylococcus aureus for detection and prophylactic functions.

In the present study, immunoglobulin Y (IgY) antibodies were raised in hens against the surface staphylococcal protein A (SpA) of Staphylococcus aureus. Anti-SpA IgY were tested in vitro for diagnostic applications, bacteriostatic, and biofilm inhibition effects. A specific and sensitive immunocapture PCR (IPCR) was developed to detect S. aureus from food, clinical, and environmental samples. Anti-SpA IgY were used for capturing S. aureus cells from different matrices. Chicken antibodies were chosen over mammalian antibodies based on its inertness to immunoglobulin (Ig)-binding property of SpA protein. No cross-reactivity was encountered with closely related Gram-positive and Gram-negative food pathogens. Inter-assay variation is < 10%. The assay was found suitable for testing on solid and liquid food samples, skin, and nasal swabs. The assay showed limit of detection of ≥ 102 CFU/mL from broth cultures and 102 to 103 CFU/ml from diverse natural samples. This assay overcomes the false positives commonly encountered while using mammalian immunoglobulins (IgG). Anti-SpA IgY antibodies were tested for their bacteriostatic effect on the growth of S. aureus. IgY antibodies at a concentration of 150 µg/ml inhibited the growth of S. aureus completely indicating the potential of IgY antibodies in neutralization of infectious pathogens. Similarly, anti-SpA IgY at MIC50 concentration reduced biofilm formation by ~ 45%. In view of advantages offered by IgY antibodies for specific detection of S. aureus in immunocapture PCR (IPCR) assay and in vitro neutralization potential of S. aureus, we recommend using IgY over conventional IgG of mammals involving S. aureus and its antigens. KEY POINTS: • IPCR with anti-SpA IgY for S. aureus was specific and sensitive for natural samples. • Anti-SpA IgY at 150 ug/ml displayed growth inhibition of S. aureus strains temporarily. • Anti-SpA IgY at MIC50 concentrations inhibited the biofilm formation partially.

Evaluation of haplotype diversity of Achatina fulica (Lissachatina) [Bowdich] from Indian sub-continent by means of 16S rDNA sequence and its phylogenetic relationships with other global populations.

Achatina fulica (Lissachatina fulica) is one of the most invasive species found across the globe causing a significant damage to crops, vegetables, and horticultural plants. This terrestrial snail is native to east Africa and spread to different parts of the world by introductions. India, a hot spot for biodiversity of several endemic gastropods, has witnessed an outburst of this snail population in several parts of the country posing a serious threat to crop loss and also to human health. With an objective to evaluate the genetic diversity of this snail, we have sampled this snail from different parts of India and analyzed its haplotype diversity by means of 16S rDNA sequence information. Apart from this, we have studied the phylogenetic relationships of the isolates sequenced in the present study in relation with other global populations by Bayesian and Maximum-likelihood approaches. Of the isolates sequenced, haplotype 'C' is the predominant one. A new haplotype 'S' from the state of Odisha was observed. The isolates sequenced in the present study clustered with its conspecifics from the Indian sub-continent. Haplotype network analyses were also carried out for studying the evolution of different haplotypes. It was observed that haplotype 'S' was associated with a Mauritius haplotype 'H', indicating the possibility of multiple introductions of A. fulica to India.

Diabetes-Role of epigenetics, genetics,and physiological factors / 中南大学学报(医学版)

Cells of organ systems are endowed with a relatively similar genome while epigenome niches keep varying chronologically and defined explicitly in the respective tissues. The genome of an individual is always influenced by parental, embryonic, tissue-specific, and environmental epigenomes and the same must have been the possible reason for invariable inquiries relating to familial, environmental and life style patterns in the preliminary investigations of diabetic complications. Unprecedented methylation of lysine residues of histones and cytosines of CpG islands of promoter DNA impede the transcription of genes and homocysteine is the metabolic key player of methyl groups. Gck and COX7A1 are the 2 examples in the present review to elucidate the epigenetic influence on the onset of diabetes. miRNAs are additional promising cellular components influencing both at transcriptional and translational levels and promoting either in favour or against (i.e., feed back) TFs, signaling factors and proteins through their pliotropic effects and thus are reported to regulate cellular physiology. miR-124a and miR-9 are primarily endemic to nervous tissue and they are now being exploited in islets for their function in executing exocytosis of insulin, which of course is one of the fundamental canons of diabetes. miR-375 persuades beta cells for glucose-induced insulin gene expression. The current approach to evaluate the constellation of genes and their products involved in diabetes in huge number of samples through GWA studies may unravel intricacies involved in the management of diabetes and its associated consequences.