Computational analysis of affinity dynamics between the variants of SARS-CoV-2 spike protein (RBD) and human ACE-2 receptor.

The novel coronavirus SARS-CoV-2 resulted in a significant worldwide health emergency known as the COVID-19 pandemic. This crisis has been marked by the widespread of various variants, with certain ones causing notable apprehension. In this study, we harnessed computational techniques to scrutinize these Variants of Concern (VOCs), including various Omicron subvariants. Our approach involved the use of protein structure prediction algorithms and molecular docking techniques, we have investigated the effects of mutations within the Receptor Binding Domain (RBD) of SARS-CoV-2 and how these mutations influence its interactions with the human angiotensin-converting enzyme 2 (hACE-2) receptor. Further we have predicted the structural alterations in the RBD of naturally occurring SARS-CoV-2 variants using the tr-Rosetta algorithm. Subsequent docking and binding analysis employing HADDOCK and PRODIGY illuminated crucial interactions occurring at the Receptor-Binding Motif (RBM). Our findings revealed a hierarchy of increased binding affinity between the human ACE2 receptor and the various RBDs, in the order of wild type (Wuhan-strain) < Beta < Alpha < Gamma < Omicron-B.1.1.529 < Delta < Omicron-BA.2.12.1 < Omicron-BA.5.2.1 < Omicron-BA.1.1. Notably, Omicron-BA.1.1 demonstrated the highest binding affinity of -17.4 kcal mol-1 to the hACE2 receptor when compared to all the mutant complexes. Additionally, our examination indicated that mutations occurring in active residues of the Receptor Binding Domain (RBD) consistently improved the binding affinity and intermolecular interactions in all mutant complexes. Analysis of the differences among variants has laid a foundation for the structure-based drug design targeting the RBD region of SARS-CoV-2.

Molecular characterization and antifungal activity of lipopeptides produced from Bacillus subtilis against plant fungal pathogen Alternaria alternata.

Over 380 host plant species have been known to develop leaf spots as a result of the fungus Alternaria alternata. It is an aspiring pathogen that affects a variety of hosts and causes rots, blights, and leaf spots on different plant sections. In this investigation, the lipopeptides from the B. subtilis strains T3, T4, T5, and T6 were evaluated for their antifungal activities. In the genomic DNA, iturin, surfactin, and fengycin genes were found recovered from B. subtilis bacterium by PCR amplification. From different B. subtilis strains, antifungal Lipopeptides were extracted, identified by HPLC, and quantified with values for T3 (24 g/ml), T4 (32 g/ml), T5 (28 g/ml), and T6 (18 g/ml). To test the antifungal activity, the isolated lipopeptides from the B. subtilis T3, T4, T5, and T6 strains were applied to Alternaria alternata at a concentration of 10 g/ml. Lipopeptides were found to suppress Alternaria alternata at rates of T3 (75.14%), T4 (75.93%), T5 (80.40%), and T6 (85.88%). The T6 strain outperformed the other three by having the highest antifungal activity against Alternaria alternata (85.88%).

Comparative study on anti-oxidant and anti-inflammatory activities of Caesalpinia crista and Centella asiatica leaf extracts.

BACKGROUND: Amyloidosis, oxidative stress and inflammation have been strongly implicated in neurodegenerative disorders like Alzheimer's disease. Traditionally, Caesalpinia crista and Centella asiatica leaf extracts are used to treat brain related diseases in India. C. crista is used as a mental relaxant drink as well as to treat inflammatory diseases, whereas C. asiatica is reported to be used to enhance memory and to treat dementia. OBJECTIVE: The present study is aimed to understand the anti-oxidant and anti-inflammatory potential of C. asiatica and C. crista leaf extracts. MATERIALS AND METHODS: Phenolic acid composition of the aqueous extracts of C. crista and C. asiatica were separated on a reverse phase C18 column (4.6 x 250 mm) using HPLC system. Antioxidant properties of the leaf extracts were determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay and the reducing potential assay. The anti-inflammatory activities of aqueous extracts of C. crista and C. asiatica were studied using 5-lipoxygenase assay. Polymorphonuclear leukocytes (PMNLs) were isolated from blood by Ficoll-Histopaque density gradient followed by hypotonic lysis of erythrocytes. RESULTS: Gallic, protocatechuic, gentisic, chlorogenic, caffeic, p-coumaric and ferulic acids were the phenolic acids identified in C. crista and C. asiatica leaf aqueous extracts. However, gallic acid and ferulic acid contents were much higher in C. crista compared to C. asiatica. Leaf extracts of C. asiatica and C. crista exhibited antioxidant properties and inhibited 5-lipoxygenase (anti-inflammatory) in a dose dependent manner. However, leaf extracts of C. crista had better antioxidant and anti-inflammatory activity compared to that of C. asiatica. The better activity of C. crista is attributed to high gallic acid and ferulic acid compared to C. asiatica. CONCLUSIONS: Thus, the leaf extract of C. crista can be a potential therapeutic role for Alzheimer's disease.

Aß(42) induced MRI changes in aged rabbit brain resembles AD brain.

Alzheimer's disease is the most common form of dementia and is structurally characterized by brain atrophy and loss of brain volume. Aß is one of the widely accepted causative factors of AD. Aß deposition is positively correlated with brain atrophy in AD. In the present study, structural brain imaging techniques such as Magnetic Resonance Imaging (MRI) were used to measure neuroanatomical alterations in Alzheimer's disease brain. MRI is a non-invasive method to study brain structure. The objective of the present study was to elucidate the role of Aß on brain structure in the aged rabbit brain. Among 20 aged rabbits, one batch (n=10) rabbits was injected chronically with Aß(1-42) and another batch (n=10) with saline. The MRI was conducted before Aß(1-42)/saline injection and after 45 days of Aß(1-42)/saline injection. All the aged rabbits underwent MRI analysis and were euthanized after 45 days. The MRI results showed a significant reduction in thickness of frontal lobe, hippocampus, midbrain, temporal lobe and increases in the lateral ventricle volume. We also conducted an MRI study on AD (n=10) and normal (n=10) cases and analyzed for the thicknesses of frontal lobe, hippocampus, midbrain, temporal lobe and lateral ventricle lobe. We found significant reductions in thickness of the frontal lobe and the hippocampus. However, no significant reduction in the thickness of midbrain, temporal lobe or increase in the lateral ventricle volume was observed compared to normal. Correlations in brain atrophy changes between rabbit brain and human AD brain were found for frontal lobe and hippocampal regions. In contrast, other regions such as midbrain, temporal lobe, and lateral ventricles were not correlated with rabbit brain atrophy changes in the corresponding regions. The relevance of these changes in AD is discussed.

A comprehensive study on the serum lipid profile and risk factor analysis for cardiovascular diseases in a cross-sectional Indian population.

Several epidemiological studies have established that Indians have a higher incidence of coronary heart disease. Because of vast differences in ethnicity, food habits and sociocultural background of Indians, it is essential that survey be conducted for profiling risk factor indicators in subjects from different parts of the country with adequate sample size. This study was carried out on CFTRI employees whose population is originally drawn from different parts of the country with diverse food habits. The population consisting of 624 subjects (514 men and 110 women) were subjected to general health check-up, blood and urine analysis under the supervision of a medical officer. Sixty-one individuals (9.77%) were found to be diabetic and 73 individuals (11.69%) were hypertensive of which 11.7% were also found to have diabetes. The mean serum cholesterol concentration in men was found to be 158 mg % and that in women was 165 mg %. Ratio of total cholesterol to HDL-cholesterol was found to be greater than 6.5 in all the cases. Blood group analysis indicated that 41.5% of the subjects belonged to O(+) group (n = 259) followed by B(+) 25.6% (n = 160), A(+) 24.6% (n = 154) and AB(+) 4.48% (n = 28). Twenty-three individuals were Rh-negative. It was observed that serum cholesterol and triglycerides were lower in O(+) groups, compared to individuals in other groups. The incidence of diabetes and hypertension in O(+) was 5.79% and 10.4%, B(+)12.5% and 15.6%, A(+) 11.0% and 12.3% and AB(+) 21.4% and 7.1% respectively. Eight individuals were found to have myocardial infarction. Among them four belonged to A(+), two to B(+) and one each to AB(+)and O(+).

Anti-amyloidogenic property of leaf aqueous extract of Caesalpinia crista.

Amyloid beta (Abeta) is the major etiological factor implicated in Alzheimer's disease (AD). Abeta(42) self-assembles to form oligomers and fibrils via multiple aggregation process. The recent studies aimed to decrease Abeta levels or prevention of Abeta aggregation which are the major targets for therapeutic intervention. Natural products as alternatives for AD drug discovery are a current trend. We evidenced that Caesalpinia crista leaf aqueous extract has anti-amyloidogenic potential. The studies on pharmacological properties of C. crista are very limited. Our study focused on ability of C. crista leaf aqueous extract on the prevention of (i) the formation of oligomers and aggregates from monomers (Phase I: Abeta(42)+extract co-incubation); (ii) the formation of fibrils from oligomers (Phase II: extract added after oligomers formation); and (iii) dis-aggregation of pre-formed fibrils (Phase III: aqueous extract added to matured fibrils and incubated for 9 days). The aggregation kinetics was monitored using thioflavin-T assay and transmission electron microscopy (TEM). The results showed that C. crista aqueous extract could able to inhibit the Abeta(42) aggregation from monomers and oligomers and also able to dis-aggregate the pre-formed fibrils. The study provides an insight on finding new natural products for AD therapeutics.

Molecular biology research in neuropsychiatry: India's contribution.

Neuropsychiatric disorders represent the second largest cause of morbidity worldwide. These disorders have complex etiology and patho-physiology. The major lacunae in the biology of the psychiatric disorders include genomics, biomarkers and drug discovery, for the early detection of the disease, and have great application in the clinical management of disease. Indian psychiatrists and scientists played a significant role in filling the gaps. The present annotation provides in depth information related to research contributions on the molecular biology research in neuropsychiatric disorders in India. There is a great need for further research in this direction as to understand the genetic association of the neuropsychiatric disorders; molecular biology has a tremendous role to play. The alterations in gene expression are implicated in the pathogenesis of several neuropsychiatric disorders, including drug addiction and depression. The development of transgenic neuropsychiatric animal models is of great thrust areas. No studies from India in this direction. Biomarkers in neuropsychiatric disorders are of great help to the clinicians for the early diagnosis of the disorders. The studies related to gene-environment interactions, DNA instability, oxidative stress are less studied in neuropsychiatric disorders and making efforts in this direction will lead to pioneers in these areas of research in India. In conclusion, we provided an insight for future research direction in molecular understanding of neuropsychiatry disorders.