Benchmarking the ability of novel compounds to inhibit SARS-CoV-2 main protease using steered molecular dynamics simulations.

Background: The SARS-CoV-2 main protease (M) is an attractive target in the COVID-19 drug development process. It catalyzes the polyprotein's translation from viral RNA and specifies a particular cleavage site. Due to the absence of identical cleavage specificity in human cell proteases, targeting M with chemical compounds can obstruct the replication of the virus.

A lesson for the maestro of the replication fork: Targeting the protein-binding interface of proliferating cell nuclear antigen for anticancer therapy.

The proliferating cell nuclear antigen (PCNA) has emerged as a promising candidate for the development of novel cancer therapeutics. PCNA is a nononcogenic mediator of DNA replication that regulates a diverse range of cellular functions and pathways through a comprehensive list of protein-protein interactions. The hydrophobic binding pocket on PCNA offers an opportunity for the development of inhibitors to target various types of cancers and modulate protein-protein interactions.

Identification of 11β-HSD1 inhibitors through enhanced sampling methods.

Aminoarylbenzosuberene (AAB) molecules were chosen for analysis to develop effective and more competent 11β-hydroxysteroid dehydrogenase (11β-HSD1) protein inhibitors. The AAB4 molecule was shown to have stronger interactions and binding affinity than standard inhibitors (co-crystallized molecules). These results were based on conventional, steered and enhanced umbrella sampling simulations.

Identification of acridinedione scaffolds as potential inhibitor of DENV-2 C protein: An in silico strategy to combat dengue.

Dengue is a prominent viral disease transmitted by mosquitoes to humans that affects mainly tropical and subtropical countries worldwide. The global spread of dengue virus (DENV) is mainly occurred by Aedes aegypti and Aedes albopictus mosquitoes. The dengue virus serotypes-2 (DENV-2) is a widely prevalent serotype of DENV, that causes the hemorrhagic fever and bleeding in the mucosa, which can be fatal.

Mechanistic behavior and subtle key events during DNA clamp opening and closing in T4 bacteriophage.

Clamp loaders ensure processive DNA replication by loading the toroidal shaped sliding clamps onto the DNA. The sliding clamps serve as a platform for the attachment of polymerases and several other proteins associated with the regulation of various cellular processes. Clamp loaders are fascinating as nanomachines that engage in protein-protein and protein-DNA interactions.

Promising protein biomarkers in the early diagnosis of Alzheimer's disease.

Alzheimer's disease (AD) is an insidious, multifactorial disease that involves the devastation of neurons leading to cognitive impairments. Alzheimer's have compounded pathologies of diverse nature, including proteins as one important factor along with mutated genes and enzymes. Although various review articles have proposed biomarkers, still, the statistical importance of proteins is missing.

A Comprehensive Review on Biology, Genetic Improvement, Agro and Process Technology of German Chamomile ( L.).

German chamomile () is recognized as a star herb due to its medicinal and aromatic properties. This plant is found across a wide range of climatic and soil conditions. Both the flower heads and blue essential oils of German chamomile possess several pharmacological properties of an anti-inflammatory, antimicrobial, antiseptic, antispasmodic and sedative, etc.

Genome-wide identification and characterization of functionally relevant microsatellite markers from transcription factor genes of Tea (Camellia sinensis (L.) O. Kuntze).

Tea, being one of the most popular beverages requires large set of molecular markers for genetic improvement of quality, yield and stress tolerance. Identification of functionally relevant microsatellite or simple sequence repeat (SSR) marker resources from regulatory "Transcription factor (TF) genes" can be potential targets to expedite molecular breeding efforts. In current study, 2776 transcripts encoding TFs harbouring 3687 SSR loci yielding 1843 flanking markers were identified from traits specific transcriptome resource of 20 popular tea cultivars.

Immuno-informatics analysis predicts B and T cell consensus epitopes for designing peptide vaccine against SARS-CoV-2 with 99.82% global population coverage.

The current global pandemic due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has taken a substantial number of lives across the world. Although few vaccines have been rolled-out, a number of vaccine candidates are still under clinical trials at various pharmaceutical companies and laboratories around the world. Considering the intrinsic nature of viruses in mutating and evolving over time, persistent efforts are needed to develop better vaccine candidates.

RBPSpot: Learning on appropriate contextual information for RBP binding sites discovery.

Identifying the factors determining the RBP-RNA interactions remains a big challenge. It involves sparse binding motifs and a suitable sequence context for binding. The present work describes an approach to detect RBP binding sites in RNAs using an ultra-fast inexact k-mers search for statistically significant seeds.

Potential of turmeric-derived compounds against RNA-dependent RNA polymerase of SARS-CoV-2: An in-silico approach.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic. Currently, there are no particular antivirals available to battle with COVID-19. The RNA-dependent RNA polymerase (RdRp) has emerged as a novel drug target due to its essential role in virus replication.

Site-directed mutagenesis (P61G) of copper, zinc superoxide dismutase enhances its kinetic properties and tolerance to inactivation by HO.

Superoxide dismutases (SODs) protect the cells by catalyzing the dismutation of harmful superoxide radicals (O) into molecular oxygen (O) and hydrogen peroxide (HO). Here, a Cu, Zn SOD (WT) from a high altitude plant (Potentilla atrosanguinea) was engineered by substituting a conserved residue proline to glycine at position 61 (P61G). The computational analysis showed higher structural flexibility and clusters in P61G than WT.

miRbiom: Machine-learning on Bayesian causal nets of RBP-miRNA interactions successfully predicts miRNA profiles.

Formation of mature miRNAs and their expression is a highly controlled process. It is very much dependent upon the post-transcriptional regulatory events. Recent findings suggest that several RNA binding proteins beyond Drosha/Dicer are involved in the processing of miRNAs.

Improving the catalytic efficiency and dimeric stability of Cu,Zn superoxide dismutase by combining structure-guided consensus approach with site-directed mutagenesis.

Superoxide dismutase (SOD) leads the front line of defense against injuries mediated by the reactive oxygen species (ROS). The SOD from a high-altitude plant Potentilla atrosanguinea is a unique thermostable enzyme. In this study, we applied a structure-guided consensus approach on Cu,Zn SOD from Potentilla atrosanguinea plant, to improve its enzymatic properties.

Time-series eco-metabolomics reveals extensive reshuffling in metabolome during transition from cold acclimation to de-acclimation in an alpine shrub.

Recording environmentally induced variations in the metabolome in plants can be a promising approach for understanding the complex patterns of metabolic regulation and their eco-physiological consequences. Here, we studied metabolome-wide changes and eco-physiological adjustments occurring across the year at high elevation environments in the leaf tissue of Rhododendron anthopogon, an alpine evergreen shrub of the Himalaya. New leaves of R.

The first draft genome of Picrorhiza kurrooa, an endangered medicinal herb from Himalayas.

Picrorhiza kurrooa is an endangered medicinal herb which is distributed across the Himalayan region at an altitude between 3000-5000 m above mean sea level. The medicinal properties of P. kurrooa are attributed to monoterpenoid picrosides present in leaf, rhizome and root of the plant.

Identification of potential plant bioactive as SARS-CoV-2 Spike protein and human ACE2 fusion inhibitors.

The Spike receptor binding domain (S-RBD) from SARS-CoV-2, a crucial protein for the entrance of the virus into target cells is known to cause infection by binding to a cell surface protein. Hence, reckoning therapeutics for the S-RBD of SARS-CoV-2 may address a significant way to target viral entry into the host cells. Herein, through in-silico approaches (Molecular docking, molecular dynamics (MD) simulations, and end-state thermodynamics), we aimed to screen natural molecules from different plants for their ability to inhibit S-RBD of SARS-CoV-2.

A computational approach for rational discovery of inhibitors for non-structural protein 1 of SARS-CoV-2.

Background: Non-structural protein 1 (Nsp1), a virulence agent of SARS-CoV-2, has emerged as an important target for drug discovery. Nsp1 shuts down the host gene function by associating with the 40S ribosomal subunit.

Methods: Molecular interactions, drug-likeness, physiochemical property predictions, and robust molecular dynamics (MD) simulations were employed to discover novel Nsp1 inhibitors.

Bioactive Molecules of Tea as Potential Inhibitors for RNA-Dependent RNA Polymerase of SARS-CoV-2.

The coronavirus disease (COVID-19), a worldwide pandemic, is caused by the severe acute respiratory syndrome-corona virus-2 (SARS-CoV-2). At this moment in time, there are no specific therapeutics available to combat COVID-19. Drug repurposing and identification of naturally available bioactive molecules to target SARS-CoV-2 are among the key strategies to tackle the notorious virus.

In-silico evaluation of bioactive compounds from tea as potential SARS-CoV-2 nonstructural protein 16 inhibitors.

Background And Aim: A novel coronavirus, called the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been found to cause COVID-19 in humans and some other mammals. The nonstructural protein 16 (NSP16) of SARS-CoV-2 plays a significant part in the replication of viruses and suppresses the ability of innate immune system to detect the virus. Therefore, inhibiting NSP16 can be a secure path towards identifying a potent medication against SARS-CoV-2.

Plant-based analogues identified as potential inhibitor against tobacco mosaic virus: A biosimulation approach.

Benzosuberene compounds with a pyrrolone group adhered to it are compounds extracted from the oils of Cedrus deodara plant, that bear inhibitory capabilities. Tobacco mosaic virus is known to affect crop production every year. The currently known inhibitors against TMV have a weak inhibition effect and also tend to be toxic towards non-target living organisms as well as the environment.

Underpinning the molecular programming attributing heat stress associated thermotolerance in tea (Camellia sinensis (L.) O. Kuntze).

The most daunting issue of global climate change is the deleterious impact of extreme temperatures on tea productivity and quality, which has resulted in a quest among researchers and growers. The current study aims to unravel molecular programming underpinning thermotolerance by characterizing heat tolerance and sensitivity response in 20 tea cultivars. The significantly higher negative influence of heat stress was recorded in a sensitive cultivar with reduced water retention (47%), chlorophyll content (33.

Genome-wide transcriptional analysis unveils the molecular basis of organ-specific expression of isosteroidal alkaloids biosynthesis in critically endangered Fritillaria roylei Hook.

Fritillaria roylei Hook. is a critically endangered high altitude Himalayan medicinal plant species with rich source of pharmaceutically active structurally diverse steroidal alkaloids. Nevertheless, except few marker compounds, the chemistry of the plant remains unexplored.

Identification of selective cyclin-dependent kinase 2 inhibitor from the library of pyrrolone-fused benzosuberene compounds: an in silico exploration.

The over-expression of cyclin-dependent kinase 2 is related to multiple cancers, which has led them to be a widely researched topic for nearly two decades. The prime focus of the present research is to design new potent and specific inhibitors against CDK2 to suppress cancer cell proliferation. In this study, we have chosen Flavopiridol, SU9516, and CVT-313 as standard inhibitors to compare with in-house synthesized pyrrolone-fused benzosuberene (PBS) compounds.

Introduction, adaptation and characterization of monk fruit (Siraitia grosvenorii): a non-caloric new natural sweetener.

Siraitia grosvenorii, an herbaceous perennial plant, native to the southern parts of China, is commonly used as a low-calorie natural sweetener. It contains cucurbitane-type triterpene glycosides known as mogrosides. The extract from monk fruit is about 300 times sweeter than sucrose.