Unveiling Annona Reticulata's Bioactive Arsenal for Enhanced Antibiotic Effects.

OBJECTIVE: To study the antibacterial and phytochemical activities of bioactive elements in the leaves of Annona reticulata Linn, a historically used Bangladeshi medicinal plant. METHODS: Shade-dried and crushed plant leaves were soaked with various solvents to obtain samples for different chemical analyses. All extracts were selected for antimicrobial, physicochemical, and Pharmacological investigations. The antimicrobial activity was evaluated using disc diffusion assay, and broth microdilution methods determined potentiation of the activities of the antibiotic antibacterial activity of the plant extracts was investigated using either gram-positive or gram-negative pathogenic wild-type bacteria. RESULTS: From the initial phytochemical and pharmacological studies, it was clear that all extracts, methanol, chloroform, and ethyl acetate, of the leaves of A. reticulata, were proven to process potent bioactive constituents. While differential antimicrobial properties were found to be possessed by all extracts, methanolic extract was the most potent one against all tested microorganisms. It also has potentiated the activities of antibiotics in E. coli. CONCLUSION: Bioactive constituents in the plant extracts were shown to possess phytochemical and antimicrobial activities. More investigation is needed to segregate the chemical components responsible for the respective phytochemical and antimicrobial activities.

Natural flavonols: actions, mechanisms, and potential therapeutic utility for various diseases.

Background: Flavonols are phytoconstituents of biological and medicinal importance. In addition to functioning as antioxidants, flavonols may play a role in antagonizing diabetes, cancer, cardiovascular disease, and viral and bacterial diseases. Quercetin, myricetin, kaempferol, and fisetin are the major dietary flavonols. Quercetin is a potent scavenger of free radicals, providing protection from free radical damage and oxidation-associated diseases. Main body of the abstract: An extensive literature review of specific databases (e.g., Pubmed, google scholar, science direct) were conducted using the keywords "flavonol," "quercetin," "antidiabetic," "antiviral," "anticancer," and "myricetin." Some studies concluded that quercetin is a promising antioxidant agent while kaempferol could be effective against human gastric cancer. In addition, kaempferol prevents apoptosis of pancreatic beta-cells via boosting the function and survival rate of the beta-cells, leading to increased insulin secretion. Flavonols also show potential as alternatives to conventional antibiotics, restricting viral infection by antagonizing the envelope proteins to block viral entry. Short conclusion: There is substantial scientific evidence that high consumption of flavonols is associated with reduced risk of cancer and coronary diseases, free radical damage alleviation, tumor growth prevention, and insulin secretion improvement, among other diverse health benefits. Nevertheless, more studies are required to determine the appropriate dietary concentration, dose, and type of flavonol for a particular condition to prevent any adverse side effects.

Implementation of computational approaches to explore the deleterious effects of non-synonymous SNPs on pRB protein.

Retinoblastoma 1 (RB1) is the first discovered tumor suppressor gene and recognized as the simple model system whose encoded defective protein can cause a pediatric cancer retinoblastoma. It functions as a negative regulator of the cell cycle through the interactions with members of the E2F transcription factors family. The protein of the RB1 gene (pRB) is engaged in various cell cycle processes including apoptosis, cell cycle arrest and chromatin remodeling. Recent studies on Retinoblastoma also exhibited multiple sets of point mutation in the associated protein due to its large polymorphic information in the local database. In this study, we identified the list of disease associated non-synonymous single nucleotide polymorphisms (nsSNPs) in RB1 by incorporating different computational algorithms, web servers, modeling of the mutants and finally superimposing it. Out of 826 nsSNPs, W516G and W563G were predicted to be highly deleterious variants in the conserved regions and found to have an impact on protein structure and protein-protein interaction. Moreover, our study concludes the effect of W516G variant was more detrimental in destabilizing protein's nature as compared to W563G variant. We also found defective binding of pRB having W516G mutation with E2F2 protein. Findings of this study will aid in shortening of the expensive experimental cost of identifying disease associated SNPs in retinoblastoma for which specialized personalized treatment or therapy can be formulated.Communicated by Ramaswamy H. Sarma.

Computational and structural based approach to identify malignant nonsynonymous single nucleotide polymorphisms associated with CDK4 gene.

Cycline-dependent kinase 4 (CDK4), an enzyme of the cycline dependent or Ser/Thr protein kinase family, plays a role in cell cycle progression (G1 phase) by phosphorylating a tumor suppressor protein called pRB. Alteration of this enzyme due to missense mutation/ nonsynonymous single nucleotide polymorphisms (nsSNPs) are responsible for various types of cancer progression, e.g. melanoma, lung cancer, and breast cancer. Hence, this study is designed to identify the malignant missense mutation of CDK4 from the single nucleotide polymorphism database (dbSNP) by incorporating computational algorithms. Out of 239 nsSNPs; G15S, D140Y and D140H were predicted to be highly malignant variants which may have a devastating impact on protein structure or function. We also found defective binding motif of these three mutants with the CDK4 inhibitor ribociclib and ATP. However, by incorporating molecular dynamic simulation, our study concludes that the superiority of G15S than the other two mutants (D140Y and D140H) in destabilizing proteins nature.

Immunoinformatics and molecular dynamics approaches: Next generation vaccine design against West Nile virus.

West Nile Virus (WNV) is a life threatening flavivirus that causes significant morbidity and mortality worldwide. No preventive therapeutics including vaccines against WNV are available for human use. In this study, immunoinformatics approach was performed to design a multi epitope-based subunit vaccine against this deadly pathogen. Human (HLA) and Mice (H-2) allele specific potential T-cell and B-cell epitopes were shortlisted through a stringent procedure. Molecular docking showed selected epitopes that have stronger binding affinity with human TLR-4. Molecular dynamics simulation confirmed the stable nature of the docked complex. Furthermore, in silico cloning analysis ensures efficient expression of desired gene in the microbial system. Interestingly, previous studies showed that two of our selected epitopes have strong immune response against WNV. Therefore, selected epitopes could be strong vaccine candidates to prevent WNV infections in human. However, further in vitro and in vivo investigations could be strengthening the validation of the vaccine candidate against WNV.

Immunoinformatics and molecular modeling approach to design universal multi-epitope vaccine for SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmittable and pathogenic human coronavirus that caused a pandemic situation of acute respiratory syndrome, called COVID-19, which has posed a significant threat to global health security. The aim of the present study is to computationally design an effective peptide-based multi-epitope vaccine (MEV) against SARS-CoV-2. The overall model quality of the vaccine candidate, immunogenicity, allergenicity, and physiochemical analysis have been conducted and validated. Molecular dynamics studies confirmed the stability of the candidate vaccine. The docked complexes during the simulation revealed a strong and stable binding interactions of MEV with human and mice toll-like receptors (TLR), TLR3 and TLR4. Finally, candidate vaccine codons have been optimized for their in silico cloning in E. coli expression system, to confirm increased expression. The proposed MEV can be a potential candidate against SARS-CoV-2, but experimental validation is needed to ensure its safety and immunogenicity status.

Implementation of in silico methods to predict common epitopes for vaccine development against Chikungunya and Mayaro viruses.

Being a Positive sense RNA virus the recent reemergence of Chikungunya and Mayaro virus has taken the concern of the leading scientific communities of the world. Though the outbreak of Mayaro virus is limited to Neotropical region only, Chikungunya is already identified in over 60 countries around the world. Besides, the lack of a strong protective treatment, misdiagnosis issue and co-circulation of both the viruses calls for a new strategy which could potentially prevent these infections from spreading. In this study, we therefore, identified the peptide based vaccine candidates e.g. epitopes for B cell and T cell from Chikungunya virus which also showed to be homologous to the Mayaro virus through immuno-informatics and computational approaches. Final epitopes identified from the most antigenic structural polyprotein of both the viruses were 5 for CD8+ T cell Epitopes (209KPGDSGRPI217, 219TGTMGHFIL227, 239ALSVVTWNK247, 98KPGRRERMC106 and 100GRRERMCMK108), 2 epitopes for CD4+ T cell (105MCMKIENDCIFEVKH119 and 502DRTLLSQQSGNVKIT516) and a single epitope for B cell (504GGRFTIPTGAGKPGDSGRPI518). Analysis of our predicted epitopes for population coverage showed prominent population coverage (92.43%) around the world. Finally, molecular docking simulation of the foreseen T cell epitopes with respondent HLA alleles secured good HLA-epitope interaction. This study was directed towards the discovery of potential antigenic epitopes which can open up a new skyline to design novel vaccines for combating both of the diseases at the same time.

Women's Knowledge, Attitude, and Perceptions Toward COVID-19 in Lower-Middle-Income Countries: A Representative Cross-Sectional Study in Bangladesh.

The coronavirus disease 2019 (COVID-19) is a global health emergency of unprecedented proportions. Countries around the world have taken extraordinary steps to control the disease. The preventive measures face challenges in low and lower middle income countries (LICs and LMICs). Especially the marginalized communities, e.g., women are the hardest hit of the virus. This study took Bangladesh as a representative LMIC and aimed to determine the level of knowledge, perception, attitude, and preparedness related to COVID-19 among the adult women in the country. Using a comprehensive questionnaire, we channeled a cross-sectional study among adult women in Bangladesh. Participant's self-reported data on the knowledge, attitude, and preparedness were tabulated and analyzed using suitable statistical tools. A total of 1,869 adults from 61 districts of Bangladesh took part in this study. Ninety seven percentage of the participants claimed to have heard of COVID-19 before it arrived in Bangladesh. Regarding the general knowledge related to COVID-19's causal agent, symptoms, and treatment, the positive response rate was nearly 80%, with a mean of 10.68 ± 1.72. Younger and educated women had better knowledge levels compared to the older and lower-educated participants (p < 0.01). More efforts are required to educate women with older age and lower socioeconomic status. An overall positive attitude and perception were observed, although a significant proportion of the participants opined that the Government's efforts in controlling the outbreak were not adequate. Although the participants had a satisfactory level of knowledge and a positive attitude in adopting preventive measures against COVID-19, greater efforts are needed from the healthcare authorities and Government.