Novel Antiviral Investigation of Annona squamosa Leaf Extract against the Dengue Virus Type-2: In vitro Study

Introduction: Dengue virus (DENV) infection is general mosquito-transmitted viral taint. It can lead to the dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Dengue is a solemn illness with no endowed antiviral medication or recognized vaccine. Therefore, we aimed to investigate the activity of Annona squamosa leaf extract (ASLE) against dengue virus type-2 (DENV-2) isolated from Surabaya, Indonesia in 2013 (NCBI accession number: KT012509). Methods: In this study, the antiviral activity of ASLE was evaluated against DENV- 2 in Vero cells using Viral ToxGlo™ Assay. In addition, we used CellTiter-Glo® Luminescent Cell Viability Assay to set the amount of viable cells in culture based on quantitation of the ATP. Results: DENV-2 replication inhibited by ASLE in Vero cells with IC50 = 73.78 μg/mL and SI = 4.49 when cells were treated two days after virus infection, whereas its CC50 for cytotoxicity to Vero cells was 331.54 μg/mL. Interestingly, this is the first report on the investigation of ASLE against DENV-2. Conclusion: In summary, ASLE demonstrated the antiviral activity against DENV-2 with less toxicity, and high possibility as a drug candidate. Therefore, it might be suggested for in vivo assessment in the progress of a potent antiviral against DENV-2

The Antioxidant, Antidiabetic, Anticancer Activities And Toxicity Of Extract Of Sargassum Duplicatum And Padina Tetrastromatica

In this current study, the two seaweed species of Sargassum duplicatum and Padina tetrastromatica were collected from oil extraction site and non-oil extraction site at Madura Island. The collected seaweeds were investigated for their phytochemical constituents, total phenolic contents (TPC), antioxidant activities, antidiabetic activities, anticancer activities, toxicities by using Folin-Ciocalteus method, the 2,2-diphernyl-1 picrylhydrazyl (DPPH), α-glucosidase enzyme, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Brine Shrimp Lethality Test (BSLT) , respectively. The crude extracts (C), normal hexane (N), ethyl acetate (E), methanol residue fractions (M) were studied. The higher TCP (589.79±7.14g and 102.36±5.77e mg GAE/g) were observed in ethyl acetate fraction of S. duplicatum and P. tetrastromatica from non-oil extraction site. Meanwhile, crude extracts and all fractions showed potent antioxidant, antidiabetic and cytotoxic activities with ethyl acetate fraction of P. tetrastromatica from non-oil extraction site displaying with the best activity (IC50 25.25±5.15a,b, 249.12±1.77b and 70.56±2.56a μg/mL, respectively). In brine shrimp assay, all fractions of S. duplicatum and P. tetrastromatica from two different sits were non-toxic after 24 h of incubation times. However, normal hexane fraction of S. duplicatum and P. tetrastromatica from oil extraction site were considered to be mild toxic while those from non-oil extraction had nontoxic after 48 h of incubation. Based on the findings of the current study, it is factual to conclude that the marine seaweed extracts from Mudra Island have antioxidant, antidiabetic, and cytotoxic activity, which could be recommended for future submission in medicinal way and exploring novel drugs from the marine product

Prediction of Aflatoxin-B1 (AFB1) Molecular Mechanism Network and Interaction to Oncoproteins Growth Factor in Hepatocellular Carcinoma

Aflatoxin-B1 (AFB1) is a common contaminant for staple foods during the storage process. Chronic exposure to AFB1 is widely known to induce the development of hepatocellular carcinoma (HCC). However, there is a lack of understanding of AFBi role in HCC mechanism. This research aims to identify protein(s) in HCC that might interact with AFB1 and to predict the pathway effected by AFB1. Analyses were performed using bioinformatics tools. SMILES notation of AFB1 was submitted into Swiss Target Prediction. Interaction among predicted proteins were analyzed by using STRING. The 3D structure of target protein was constructed by homology modeling. Reverse docking was performed, and the result was ranked based on binding affinity score. Furthermore, protein interaction network was constructed and analyzed by using Cytoscape. Results showed that three protein groups were predicted as target of AFB1, such as kinases, phosphatases, and G protein-coupled receptor with probability of 46.7%, 20%, and 6.7%, respectively. Seven proteins of kinases were strongly related to HCC, including RAF1, MAPK1, MAPK3, AKT1, EGFR, GSK3B, and mTOR. Reverse docking considered the AKT1-AFB1 as the most potential complex with the lowest affinity score -10.2 kcal.mol-1. It has hydrophobic bonds in Trp80, Val270, Tyr272, Asp292, Thr211, Leu210, Leu264, and Lys268 residues, whereas hydrogen bond in Ser205 residues. Moreover, further analysis demonstrated that interaction of AKT1-AFB1 is related to the metastasis pathway in HCC mechanism