Sour Tamarind Is More Antihypertensive than the Sweeter One, as Evidenced by In Vivo Biochemical Indexes, Ligand-Protein Interactions, Multitarget Interactions, and Molecular Dynamic Simulation.

This research investigated the antihypertensive effects of tamarind products and compared their potentials based on an animal model's data verified by molecular docking, multitarget interactions, and dynamic simulation assays. GC-MS-characterized tamarind products were administered to cholesterol-induced hypertensive albino rat models. The two-week-intervened animals were dissected to collect their serum and organs and respectively subjected to analyses of their hypertension-linked markers and tissue architectures. The lead biometabolites of tamarinds interacted with eight target receptors in the molecular docking and dynamic simulation studies and with multitarget in the network pharmacological analyses. The results show that the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), C-reactive protein (CRP), troponin I, and lipid profiles were maximally reinstated by the phenolic-enriched ripened sour tamarind extract compared to the sweet one, but the seed extracts had a smaller influence. Among the tamarind's biometabolites, ϒ-sitosterol was found to be the best ligand to interact with the guanylate cyclase receptor, displaying the best drug-likeliness with the highest binding energy, -9.3 Kcal. A multitargeted interaction-based degree algorithm and a phylogenetic tree of pathways showed that the NR3C1, REN, PPARG, and CYP11B1 hub genes were consistently modulated by ϒ-sitosterol to reduce hypertension and related risk factors. The dynamic simulation study showed that the P-RMSD values of ϒ-sitosterol-guanylate cyclase were stable between 75.00 and 100.00 ns at the binding pocket. The findings demonstrate that ripened sour tamarind extract may be a prospective antihypertensive nutraceutical or supplement target affirmed through advanced preclinical and clinical studies.

Whole proteome screening and identification of potential epitopes of SARS-CoV-2 for vaccine design-an immunoinformatic, molecular docking and molecular dynamics simulation accelerated robust strategy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the most cryptic pandemic outbreak of the 21st century, has gripped more than 1.8 million people to death and infected almost eighty six million. As it is a new variant of SARS, there is no approved drug or vaccine available against this virus. This study aims to predict some promising cytotoxic T lymphocyte epitopes in the SARS-CoV-2 proteome utilizing immunoinformatic approaches. Firstly, we identified 21 epitopes from 7 different proteins of SARS-CoV-2 inducing immune response and checked for allergenicity and conservancy. Based on these factors, we selected the top three epitopes, namely KAYNVTQAF, ATSRTLSYY, and LTALRLCAY showing functional interactions with the maximum number of MHC alleles and no allergenicity. Secondly, the 3D model of selected epitopes and HLA-A*29:02 were built and Molecular Docking simulation was performed. Most interestingly, the best two epitopes predicted by docking are part of two different structural proteins of SARS-CoV-2, namely Membrane Glycoprotein (ATSRTLSYY) and Nucleocapsid Phosphoprotein (KAYNVTQAF), which are generally target of choice for vaccine designing. Upon Molecular Docking, interactions between selected epitopes and HLA-A*29:02 were further validated by 50 ns Molecular Dynamics (MD) simulation. Analysis of RMSD, Rg, SASA, number of hydrogen bonds, RMSF, MM-PBSA, PCA, and DCCM from MD suggested that ATSRTLSYY is the most stable and promising epitope than KAYNVTQAF epitope. Moreover, we also identified B-cell epitopes for each of the antigenic proteins of SARS CoV-2. Findings of our work will be a good resource for wet lab experiments and will lessen the timeline for vaccine construction.Communicated by Ramaswamy H. Sarma.

Nature-Derived Hit, Lead, and Drug-Like Small Molecules: Current Status and Future Aspects Against Key Target Proteins of Coronaviruses.

BACKGROUND: COVID-19 pandemic, the most unprecedented event of the year 2020, has brought millions of scientists worldwide in a single platform to fight against it. Though several drugs are now in the clinical trial, few vaccines are available on the market already, but the lack of an effect of those is making the situation worse. AIM OF THE STUDY: In this review, we demonstrated comprehensive data of natural antiviral products showing activities against different proteins of Human Coronaviruses (HCoV) that are responsible for its pathogenesis. Furthermore, we categorized the compounds into the hit, lead, and drug based on the IC50/EC50 value, drug-likeness, and lead-likeness test to portray their potentiality to be a drug. We also demonstrated the present status of our screened antiviral compounds with respect to clinical trials and reported the lead compounds that can be promoted to clinical trial against COVID-19. METHODS: A systematic search strategy was employed focusing on Natural Products (NPs) with proven activity (in vitro, in vivo, or in silico) against human coronaviruses, in general, and data were gathered from databases like PubMed, Web of Science, Google Scholar, SciVerse, and Scopus. Information regarding clinical trials retrieved from the Clinical Trial Database. RESULTS: Total "245" natural compounds were identified initially from the literature study. Among them, Glycyrrhizin, Caffeic acid, Curcumin is in phase 3, and Tetrandrine, Cyclosporine, Tacrolimus, Everolimus are in phase 4 clinical trial. Except for Glycyrrhizin, all compounds showed activity against COVID-19. CONCLUSION: In summary, our demonstrated specific small molecules with lead and drug-like capabilities clarified their position in the drug discovery pipeline and proposed future research against COVID-19.

Comparative proteomic analysis to annotate the structural and functional association of the hypothetical proteins of S. maltophilia k279a and predict potential T and B cell targets for vaccination.

Stenotrophomonas maltophilia is a multidrug-resistant bacterium with no precise clinical treatment. This bacterium can be a vital cause for death and different organ failures in immune-compromised, immune-competent, and long-time hospitalized patients. Extensive quorum sensing capability has become a challenge to develop new drugs against this pathogen. Moreover, the organism possesses about 789 proteins which function, structure, and pathogenesis remain obscured. In this piece of work, we tried to enlighten the aforementioned sectors using highly reliable bioinformatics tools validated by the scientific community. At first, the whole proteome sequence of the organism was retrieved and stored. Then we separated the hypothetical proteins and searched for the conserved domain with a high confidence level and multi-server validation, which resulted in 24 such proteins. Furthermore, all of their physical and chemical characterizations were performed, such as theoretical isoelectric point, molecular weight, GRAVY value, and many more. Besides, the subcellular localization, protein-protein interactions, functional motifs, 3D structures, antigenicity, and virulence factors were also evaluated. As an extension of this work, 'RTFAMSSER' and 'PAAPQPSAS' were predicted as potential T and B cell epitopes, respectively. We hope our findings will help in better understating the pathogenesis and smoothen the way to the cure.