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.

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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Clostridium botulinum is anaerobic pathogenic bacterium causing food-born botulism in human and animals by producing botulinum neurotoxins A-H, C2, and C3 cytotoxins. Physiological group III strains (type C and D) of this bacterium are capable of producing C2 and C3 toxins in cattle and avian. Herein, we have revealed the structure-function disparity of C3 toxins from two different C. botulinum type C phage (CboC) and type D phage (CboD) to design avirulent toxins rationally. Structure-function discrepancy of the both toxins was computationally evaluated from their homology models based on the conservation in sequence-structure-function relationships upon covariation and point mutations. It has shown that 8 avirulent mutants were generated from CboC of 34 mutants while 27 avirulent mutants resulted from CboD mutants. No major changes were found in tertiary structure of these toxins; however, some structural variations appeared in the coiled and loop regions. Correlated mutation on the first residue would disorder or revolutionize the hydrogen bonding pattern of the coevolved pairs. It suggested that the residues coupling in the local structural environments were compensated with coevolved pairs so as to preserve a pseudocatalytic function in the avirulent mutants. Avirulent mutants of C3 toxins have shown a stable structure with a common blue print of folding process and also attained a near-native backrub ensemble. Thus, we concluded that selecting the site-directed mutagenesis sites are very important criteria for designing avirulent toxins, in development of rational subunit vaccines, to cattle and avian, but the vaccine specificity can be determined by the C3 toxins of C. botulinum harboring phages.

The sponge (Porifera) microbiome is an indicator of both natural and anthropogenic stressors. Studying Baikal sponge microbial communities could help reveal if there is a connection between bacterial symbionts and a mass sponge bleaching event that was recently detected; 16S rRNA sequencing was performed among healthy and diseased freshwater sponges of Lubomirskia baikalensis and Baikalospongia intermedia, which were collected from Lake Baikal, Russia. A phylum-based taxonomic classification showed that Chlorophyta, Acidobacteria, Bacteroidetes, Actinobacteria and Cyanobacteria were most abundant across samples. When comparing healthy and diseased L. baikalensis samples, large variations in microbial composition were found at the phylum level. Comparative analyses, which were performed for the first time for B. intermedia, showed a decrease in Chlorophyta (unicellular green algae) and an increase in Bacteroidetes and Cyanobacteria in diseased specimens. At the genus level, the Opitutus (Verrucomicrobia), Planctomyces, and Nitrospira content increased in all diseased sponges, which reflected a general tendency toward an increase in Cyanobacteria in diseased sponges. Comparative analysis of the diseased and healthy sponge metagenomes showed that diseased sponges underwent various nonspecific changes in bacterial composition. The bacterial community composition is probably influenced by sponge type and degree of disease affection.

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