Coronavirus disease (COVID-19) rapidly expands to a global pandemic and its impact on public health varies from country to country. It is caused by a new virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is imperative for relapsing current antiviral therapeutics owing to randomized genetic drift in global SARS-CoV-2 isolates. A molecular mechanism behind the emerging genomic variants is not yet understood for the prioritization of selective antivirals. The present computational study was aimed to repurpose existing antivirals for Indian SARS-CoV-2 isolates by uncovering a hijack mechanism based on structural and functional characteristics of protein variants. Forty-one protein mutations were identified in 12 Indian SARS-CoV-2 isolates by analysis of genome variations across 460 genome sequences obtained from 30 geographic sites in India. Two unique mutations such as W6152R and N5928H found in exonuclease of Surat (GBRC275b) and Gandhinagar (GBRC239) isolates. We report for the first time the impact of folding rate on stabilizing/retaining a sequence-structure-function-virulence link of emerging protein variants leading to accommodate hijack ability from current antivirals. Binding affinity analysis revealed the effect of point mutations on virus infectivity and the drug-escaping efficiency of Indian isolates. Emodin and artinemol suggested herein as repurposable antivirals for the treatment of COVID-19 patients infected with Indian isolates. Our study concludes that a protein folding rate is a key structural and evolutionary determinant to enhance the receptor-binding specificity and ensure hijack ability from the prevalent antiviral therapeutics.

The symptomatology of novel Severe Acute Respiratory Syndrome Corona virus type 2 infection runs the entire gamut of mild to moderate and serious illness among the affected individuals. As listed in recent literature, respiratory, cardiovascular, gastrointestinal, olfactory and gustatory systems are commonly involved. With the growing knowledge about the disease, varied manifestations have been identified and lately, otorhinolaryngology dysfunctions in COVID 19 have been described. Hearing loss in COVID era is one of the emerging areas of concern and calls for further research in the field for the better understanding and treatment of this entity. This study was designed to assess the audiological profile among 100 mild to moderately affected COVID-19 individuals, so as to make a contribution to the emerging literature on otologic manifestations in COVID 19. In our case series, high frequency hearing loss and referred OAE was noted among significant number of COVID 19 positive patients. This was even observed in patients without any otologic symptoms. Hence, early identification and intervention if required helps to give a better quality of life to the patient.

Methanobacterium formicicum (Methanobacteriaceae family) is an endosymbiotic methanogenic Archaean found in the digestive tracts of ruminants and elsewhere. It has been significantly implicated in global CH 4 emission during enteric fermentation processes. In this review, we discuss current genomic and metabolic aspects of this microorganism for the purpose of the discovery of novel veterinary therapeutics. This microorganism encompasses a typical H 2 scavenging system, which facilitates a metabolic symbiosis across the H 2 producing cellulolytic bacteria and fumarate reducing bacteria. To date, five genome-scale metabolic models (iAF692, iMG746, iMB745, iVS941 and iMM518) have been developed. These metabolic reconstructions revealed the cellular and metabolic behaviors of methanogenic archaea. The characteristics of its symbiotic behavior and metabolic crosstalk with competitive rumen anaerobes support understanding of the physiological function and metabolic fate of shared metabolites in the rumen ecosystem. Thus, systems biological characterization of this microorganism may provide a new insight to realize its metabolic significance for the development of a healthy microbiota in ruminants. An in-depth knowledge of this microorganism may allow us to ensure a long term sustainability of ruminant-based agriculture.

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Bacterial ADP-ribosyltransferases (BADPRTs) are extensively contributed to determine the strain-specific virulence state and pathogenesis in human hosts. Understanding molecular evolution and functional diversity of the BADPRTs is an important standpoint to describe the fundamental behind in the vaccine designing for bacterial infections. In the present study, we have evaluated the origin and functional evolution of conserved domains within the BADPRTs by analyzing their sequence-function relationship. To represent the evolution history of BADPRTs, phylogenetic trees were constructed based on their protein sequence, structure and conserved domains using different evolutionary programs. Sequence divergence and genetic diversity were studied herein to deduce the functional evolution of conserved domains across the family and superfamily. The results of sequence similarity search have shown that three hypothetical proteins (above 90%) were identical to the members of BADPRTs and their functions were annotated by phylogenetic approach. Phylogenetic analysis of this study has revealed the family members of BADPRTs were phylogenetically related to one another, functionally diverged within the same family, and dispersed into closely related bacteria. The presence of core substitution pattern in the conserved domains would determine the family-specific function of BADPRTs. Functional diversity of the BADPRTs was exclusively distinguished by Darwinian positive selection (diphtheria toxin C and pertussis toxin S) and neutral selection (arginine ADP-ribosyltransferase, enterotoxin A and binary toxin A) acting on the existing domains. Many of the family members were sharing their sequence-specific features from members in the arginine ADP-ribosyltransferase family. Conservative functions of members in the BADPRTs have shown to be expanded only within closely related families, and retained as such in pathogenic bacteria by evolutionary process (domain duplication or recombination events). Hence, we conclude that evolutionary significance of the members in the BADPRTs would provide an insight for experimental set-up on site-directed mutagenesis and vaccine engineering.

Methanobrevibacter ruminantium M1 (MRU) is a rod-shaped rumen methanogen with the ability to use H2 and CO2, and formate as substrates for methane formation in the ruminants. Enteric methane emitted from this organism can also be influential to the loss of dietary energy in ruminants and humans. To date, there is no successful technology to reduce methane due to a lack of knowledge on its molecular machinery and 73% conserved hypothetical proteins (HPs; operome) whose functions are still not ascertained perceptively. To address this issue, we have predicted and assigned a precise function to HPs and categorize them as metabolic enzymes, binding proteins, and transport proteins using a combined bioinformatics approach. The results of our study show that 257 (34%) HPs have well-defined functions and contributed essential roles in its growth physiology and host adaptation. The genome-neighborhood analysis identified 6 operon-like clusters such as hsp, TRAM, dsr, cbs and cas, which are responsible for protein folding, sudden heat-shock, host defense, and protection against the toxicities in the rumen. The functions predicted from MRU operome comprised of 96 metabolic enzymes with 17 metabolic subsystems, 31 transcriptional regulators, 23 transport, and 11 binding proteins. Functional annotation of its operome is thus more imperative to unravel the molecular and cellular machinery at the systems-level. The functional assignment of its operome would advance strategies to develop new anti-methanogenic targets to mitigate methane production. Hence, our approach provides new insight into the understanding of its growth physiology and lifestyle in the ruminants and also to reduce anthropogenic greenhouse gas emissions worldwide.

30 Polysomnography proved OSA patients, age between 20 and 60 years have been selected for Drug Induced Sleep Endoscopy (DISE) after taking informed consent for proposed surgery. Inj propofol infusion given throughout the DISE procedure and upper airway nasal endoscopy performed for assessment of site of collapse (Retropalatal, Retrolingual, Hypopharyngral), type of collapse (circumferential, lateral) and severity of obstruction, Lowest SpO, apnoeic episodes and DISE findings were recorded. Out of these thirty patients 90% were male and 10% were female, observed that 66.7% of males and 40.7% of females belonged to 31-40 age group, and BMI of 63.3% of patient population were overweight, 20% were obese and 5% were normal. Mean fall in SpO was 90.20 ± 2.77 in normal subjects, 83.05 ± 5.14 in overweight subjects and 68.83 ± 9.11 in obese subjects. Normal subjects had 0.4 ± 0.9 apnoeic episodes, overweight subjects had 0.9 ± 1.6 episodes and obese subjects had 4.0 ± 2 apnoeic episodes. We observed that 40% had retropalatal airway collapse, 23.3% had airway obstruction at the base of the tongue, 20% had airway obstruction with floppy epiglottis, 12% multiple level collapse, 6.7% of patient population had grade 4 enlarged tonsils, 3.3% had lateral pharyngeal wall collapse, and 0% hypopharyngeal collapse. Out of 30, 29 Patients underwent surgery (Expansion sphincter pharyngo plasty-14, Hyoid advancement-4, Uuvulopalatoplasty-10, Epiglottic surgery-6, Zeta pharyngoplasty-2, midline glossectomy-3, Endoscopic septoplasty-5, Inferio turbinoplasty-2, LASSER Assisted lingual tonsillectomy-1), All these 29 patient were followed for 3 months, at the end of 3rd month again Each subject was evaluated with a baseline Epworth Sleepiness Scale and LEVEL-3 PSG, the results were impressive with statistically significant. DISE is a dynamic, safe, and easy-to-perform technique that visualizes, the anatomical sites of snoring or apneas for assessment site of collapse (Retropalatal, Retrolingual, Hypopharyngral), type of collapse (Circumferential, Lateral) and severity of obstruction and guides the design of a tailor-made treatment plan for a OSA SURGEON in individual cases, which will improves perioperative outcome.

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