design and discovery of pan coronavirus small molecule anti-virals targeting 3CL protease.

Coronaviruses (CoV), belonging to the family , were not considered dangerous pathogens until the outbreaks of SARS, MERS, and more recently, COVID-19. The coronaviruses causing these respective diseases/syndromes, SARS, MERS, and SARS-CoV2, share high sequence and structural similarities. COVID-19 continues to have a global impact on human health and the economy.

Dengue outbreak and severity prediction: current methods and the future scope.

Dengue virus (DENV) is the causative agent of dengue fever and severe dengue. Every year, millions of people are infected with this virus. There is no vaccine available for this disease.

Effect of ACGT motif in spatiotemporal regulation of AtAVT6D, which improves tolerance to osmotic stress and nitrogen-starvation.

Plasma membrane-localized AtAVT6D importing aspartic acid can be targeted to develop plants with enhanced osmotic and nitrogen-starvation tolerance. AtAVT6D promoter can be exploited as a stress-inducible promoter for genetic improvements to raise stress-resilient crops. The AtAVT6 family of amino acid transporters in Arabidopsis thaliana has been predicted to export amino acids like aspartate and glutamate.

An discovery of potential 3CL protease inhibitors of SARS-CoV-2 based upon inactivation of the cysteine 145-Histidine 41 catalytic dyad.

Coronavirus disease 19 (COVID19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, several countries are at risk of the pandemic caused by this virus. In the absence of any vaccine or virus-specific antiviral treatments, the need is to fast track search for potential drug candidates to combat the virus.

The RNA Secondary Structure Analysis Reveals Potential for Emergence of Pathogenic Flaviviruses.

The Flavivirus genus is divided into four groups: Mosquito-borne flaviviruses, Tick-borne flaviviruses, no-known vector flaviviruses, and Insect specific flaviviruses. Millions of people are affected worldwide every year due to the flaviviral infections. The 5' UTR of the RNA genome plays a critical role in the biology of flaviviruses.

LipGene: Lipschitz Continuity Guided Adaptive Learning Rates for Fast Convergence on Microarray Expression Data Sets.

Hyperparameter tuning, specifically tuning of learning rate, can often be a time-consuming process, especially when dealing with large data sets. A mathematical foundation in the choice of learning rate can minimize tuning efforts. We propose the application of a novel adaptive learning rate paradigm, guided by Lipschitz continuity of the loss functions (LipGene), to the task of Gene Expression Inference using shallow neural networks.

Global analysis of RNA-protein interactions in TNF-α induced alternative splicing in metabolic disorders.

In this report, using the database of RNA-binding protein specificities (RBPDB) and our previously published RNA-seq data, we analyzed the interactions between RNA and RNA-binding proteins to decipher the role of alternative splicing in metabolic disorders induced by TNF-α. We identified 13 395 unique RNA-RBP interactions, including 385 unique RNA motifs and 35 RBPs, some of which (including MBNL-1 and 3, ZFP36, ZRANB2, and SNRPA) are transcriptionally regulated by TNF-α. In addition to some previously reported RBPs, such as RBMX and HuR/ELAVL1, we found a few novel RBPs, such as ZRANB2 and SNRPA, to be involved in the regulation of metabolic syndrome-associated genes that contain an enrichment of tetrameric RNA sequences (AUUU).

The RNA secondary structural variation in the cyclization elements of the dengue genome and the possible implications in pathogenicity.

Dengue virus (DENV), the causative agent of dengue fever and severe dengue, exists as four antigenically different serotypes. These serotypes are further classified into genotypes and have varying degrees of pathogenicity. The 5' and 3' ends of the genomic RNA play a critical role in the viral life cycle.

Type II diabetes mellitus and obesity: Common links, existing therapeutics and future developments.

Type II diabetes mellitus (T2DM) and obesity are two common pathophysiological conditions of metabolic syndrome (MetS), a collection of similar metabolic dysfunctions due to sedentary lifestyle and overnutrition. Obesity arises from improper adipogenesis which otherwise has a crucial role in maintaining proper metabolic functions. Downstream events arising from obesity have been linked to T2DM.

Finding small molecules with pan-serotype activity to target Dengue non-structural protein 1.

Dengue virus (DENV) is a mosquito-borne flavivirus which causes Dengue fever and severe Dengue. It exists as four antigenically different serotypes that are further classified into genotypes with varying degrees of pathogenicity. The non-structural protein 1 (NS1) of DENV has an important role in viral replication and its pathogenesis.

A Data Driven Model for Predicting RNA-Protein Interactions based on Gradient Boosting Machine.

RNA protein interactions (RPI) play a pivotal role in the regulation of various biological processes. Experimental validation of RPI has been time-consuming, paving the way for computational prediction methods. The major limiting factor of these methods has been the accuracy and confidence of the predictions, and our in-house experiments show that they fail to accurately predict RPI involving short RNA sequences such as TERRA RNA.

Structure modulation of helix 69 from Escherichia coli 23S ribosomal RNA by pseudouridylations.

Helix 69 (H69) is a 19-nt stem-loop region from the large subunit ribosomal RNA. Three pseudouridine (Ψ) modifications clustered in H69 are conserved across phylogeny and known to affect ribosome function. To explore the effects of Ψ on the conformations of Escherichia coli H69 in solution, nuclear magnetic resonance spectroscopy was used to reveal the structural differences between H69 with (ΨΨΨ) and without (UUU) Ψ modifications.

Molecular determinants of HIV-1 NCp7 chaperone activity in maturation of the HIV-1 dimerization initiation site.

Human immunodeficiency virus genome dimerization is initiated through an RNA-RNA kissing interaction formed via the dimerization initiation site (DIS) loop sequence, which has been proposed to be converted to a more thermodynamically stable linkage by the viral p7 form of the nucleocapsid protein (NC). Here, we systematically probed the role of specific amino acids of NCp7 in its chaperone activity in the DIS conversion using 2-aminopurine (2-AP) fluorescence and nuclear magnetic resonance spectroscopy. Through comparative analysis of NCp7 mutants, the presence of positively charged residues in the N-terminus was found to be essential for both helix destabilization and strand transfer functions.

Pseudouridines in rRNA helix 69 play a role in loop stacking interactions.

The (1)H NMR spectra of RNAs representing E. coli 23S rRNA helix 69 with [1,3-(15)N]pseudouridine modification at specific sites reveal unique roles for pseudouridine in stabilizing base-stacking interactions in the hairpin loop region.

AMBER Force Field Parameters for the Naturally Occurring Modified Nucleosides in RNA.

Classical molecular dynamics (MD) simulations are useful for characterizing the structure and dynamics of biological macromolecules, ultimately, resulting in elucidation of biological function. The AMBER force field is widely used and has well-defined bond length, bond angle, partial charge, and van der Waals parameters for all the common amino acids and nucleotides, but it lacks parameters for many of the modifications found in nucleic acids and proteins. Presently there are 107 known naturally occurring modifications that play important roles in RNA stability, folding, and other functions.