• Ramanathan Sowdhamini

      Articles written in Journal of Biosciences

    • Genome inventory and analysis of nuclear hormone receptors in Tetraodon nigroviridis

      Raghu Prasad Rao Metpally Ramakrishnan Vigneshwar Ramanathan Sowdhamini

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      Nuclear hormone receptors (NRs) form a large superfamily of ligand-activated transcription factors, which regulate genes underlying a wide range of (patho) physiological phenomena. Availability of the full genome sequence of Tetraodon nigroviridis facilitated a genome wide analysis of the NRs in fish genome. Seventy one NRs were found in Tetraodon and were compared with mammalian and fish NR family members. In general, there is a higher representation of NRs in fish genomes compared to mammalian ones. They showed high diversity across classes as observed by phylogenetic analysis. Nucleotide substitution rates show strong negative selection among fish NRs except for pregnane X receptor (PXR), estrogen receptor (ER) and liver X receptor (LXR). This may be attributed to crucial role played by them in metabolism and detoxification of xenobiotic and endobiotic compounds and might have resulted in slight positive selection. Chromosomal mapping and pairwise comparisons of NR distribution in Tetraodon and humans led to the identification of nine syntenic NR regions, of which three are common among fully sequenced vertebrate genomes. Gene structure analysis shows strong conservation of exon structures among orthologoues. Whereas paralogous members show different splicing patterns with intron gain or loss and addition or substitution of exons played a major role in evolution of NR superfamily.

    • Computational search for potential COVID-19 drugs from FDAapproved drugs and small molecules of natural origin identifies several anti-virals and plant products

      ABHISHEK SHARMA VIKAS TIWARI RAMANATHAN SOWDHAMINI

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      The world is currently facing the COVID-19 pandemic, for which mild symptoms include fever and dry cough.In severe cases, it could lead to pneumonia and ultimately death in some instances. Moreover, the causativepathogen is highly contagious and there are no drugs or vaccines for it yet. The pathogen, SARS-CoV-2, is oneof the human coronaviruses which was identified to infect humans first in December 2019. SARS-CoV-2shares evolutionary relationship to other highly pathogenic viruses such as Severe Acute Respiratory Syndrome(SARS) and Middle East respiratory syndrome (MERS). We have exploited this similarity to model atarget non-structural protein, NSP1, since it is implicated in the regulation of host gene expression by the virusand hijacking of host machinery. We next interrogated the capacity to repurpose around 2300 FDA-approveddrugs and more than 3,00,000 small molecules of natural origin towards drug identification through virtualscreening and molecular dynamics. Interestingly, we observed simple molecules like lactose, previously knownanti-virals and few secondary metabolites of plants as promising hits. These herbal plants are already practicedin Ayurveda over centuries to treat respiratory problems and inflammation. Disclaimer: we would not like torecommend uptake of these small molecules for suspect COVID patients until it is approved by competentnational or international authorities.

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