Bioinformatics Exploration of Ginseng: A Review

Ginseng contains an extraordinarily complex mixture of chemical constituents that can vary with the species used, the place of origin, and the growing conditions. Various computational analyses which include genomics, transcriptomics, proteomics and bioinformatics have been used to study ginseng plant. A genome-scale metabolic network offers a holistic view of ginsenoside biosynthesis, helps to predict genes associated with the production of pharmacologically vital dammarane-type ginsenosides, and provides insight for improving medicinal values of ginseng by genomics-based breeding. The draft genomic architecture of tetraploid P. ginseng cultivar (cv.) Chunpoong (ChP) by de novo genome assembly, was found to be 2.98 Gbp and consist of 59,352 annotated genes. Presently, bioinformatics exploration of ginseng includes studies on its P-glycoproteins, the impact of cytochrome P-450 on ginseng pharmacokinetics, as well as target prediction and differential gene expression network analyses. This study applauded Betasitosterol and Daucosterin as ginseng bioactive constituents that have several potential pharmacological effects in human, by modulating several proteins which include androgen receptor, HMG-CoA reductase, interlukin-2, and consequently impact the signaling cascade of several kinases such as mitogen-activated protein kinases (MAPKs), as well as many transcription factors such as polycomb protein SUZ12

Human adenovirus DNA polymerase is evolutionarily and functionally associated with human telomerase reverse transcriptase based on in silico molecular characterization that implicate abacavir and zidovudine

Human adenoviruses (HAdVs) are non-enveloped, small double stranded DNA (dsDNA) viruses that cause asymptomatic infections, clinical syndromes and significant susceptibility to infections in immunocompromised people. The aim of the present study was to identify critical host proteins and HAdV hypothetical proteins that could be developed as potential host-viral targets for antiHAdV therapy. Here, the function of selected hypothetical proteins of HAdV based on phylogenetic relationship with the therapeutic targets of antiretroviral drugs of human immunodeficiency virus (HIV) was predicted computationally, and characterized the molecular dynamics and binding affinity of DNA polymerase of HAdV. Thirty-eight hypothetical proteins (HPs) of human adenovirus (HAdV) were used in this study. The results showed that HAdV DNA polymerase (P03261) is related to Human TERT (O14746) and HLA-B (P01889) genes. The protein-protein interaction of human five molecular targets (PNP, TERT, CCR5, HLA-B, and NR1I2) of ARVDs are well-coordinated/networked with CD4, AHR, FKBP4, NR3C1, HSP90AA1, and STUB1 proteins in the anti-HIV infection mechanism. The results showed that the free energy score of abacavir and zidovudine binding to HAdV DNA polymerase are −5.8 and −5.4 kcal mol-1 respectively. Also, the control drug, cidofovir and ganciclovir have less binding affinity for DNA polymerase of HAdV when compare to that of abacavir and zidovudine. Similarity was observed in the binding of abacavir and zidovudine to HAdV DNA polymerase (ASP742, ALA743, LEU772, ARG773 and VAL776). In conclusion, combination of abacavir and zidovudine was predicted to be potential therapy for controlling HAdV infection targeting HAdV DNA polymerase

Melanogenesis, Its Regulatory Process, and Insights on Biomedical, Biotechnological, and Pharmacological Potentials of Melanin as Antiviral Biochemical

Melanin is s most widely distributed pigment and is found in bacteria, fungi, plants, and animals. Melanogenesis is under complex regulatory control by multiple agents interacting through pathways activated by hormonal and receptor-dependent and -independent mechanisms. There are about 20 genes that are involved in the biochemical pathway of melanogenesis and its regulation, which include: tyrosinase, microphthalmia-associated transcription factor, melanocortin1 receptor, adenylate cyclase, protein kinase A. Human melanogenesis regulatory proteins such as MAPK1, CREB3, and CREBP, have binary interaction with the protein of herpesvirus, hepatitis C virus, Human immunodeficiency virus type 1, Simian virus 40, and Human adenovirus A and C. Melanin is a double-edged sword in host-pathogen interaction (e.g., human-bacteria and/or fungi interaction). The inducers of upregulation of melanogenesis include fluvoxamine, famotidine, terbutaline, heliotrine, sirolimus, dicoumarol, Prestwick-860, carbimazole, (-)-MK-801, rilmenidine, hydrastine hydrochloride, haloperidol, scopolamine N-oxide, raubasine, and dihydroergocristine. In melanogenesis, GSK3B, CSNK2A, MAPK1, MAPK3, MAPK14, ERK1, and HIPK2 were the major kinases, while RUNX1, GATA1, and REST, SUN12, and RCOR1 were the major transcription factors. This study has reviewed the melanogenesis pathway, its regulations as well as applications to viral infection. The antiviral activity of melanin and its complex in the presence of antibacterial and antifungal compounds should be investigated to further provide insight for biomedical, biotechnological, and pharmacological applications

A Mini Review of Novel Topoisomerase II Inhibitors as Future Anticancer Agents

Several reviews of inhibitors of topoisomerase II have been published, covering research before 2018. Therefore, this review is focused primarily on more recent publications with relevant points from the earlier literature. Topoisomerase II is an established target for anticancer drugs, which are further subdivided into poisons and catalytic inhibitors. While most of the topoisomerase II-based drugs in clinical use are mostly topoisomerase II poisons, their mechanism of action has posed severe concern due to DNA damaging potential, including the development of multi-drug resistance. As a result, we are beginning to see a gradual paradigm shift towards non-DNA damaging agents, such as the lesser studied topoisomerase II catalytic inhibitors. In addition, this review describes some novel selective catalytic topoisomerase II inhibitors. The ultimate goal is to bring researchers up to speed by curating and delineating new scaffolds as the leads for the optimization and development of new potent, safe, and selective agents for the treatment of cancer

Bioinformatics exploration of olive oil: molecular targets and properties of major bioactive constituents

Olive oil possesses medicinal properties which include antimicrobial, antioxidant and anti-inflammatory, anti-diabetes, and anti-cardiovascular diseases. Oleic acid is the most abundant (95%) constituent of olive oil and others include linoleic acid, oleuropein, oleanolic acid, maslinic acid, melatonin, and others. The objective of this study is to predict the molecular targets and properties of key bioactive components of olive oil in human. Bioinformatics methods, which involved pharmacokinetics prediction, target prediction and gene network analyses, were used. The results showed that oleic acid has similar targets with linoleic acid, and showed significant probability of binding to several targets such as fatty acid-binding proteins in the adipose, epidermal, liver and muscle as well as alpha, delta and gamma peroxisome proliferator-activated receptors (PPARs). Carbonic anhydrase showed to be the only significant target of tyrosol, while protein-tyrosine phosphatase 1B, and CD81 antigen were targeted by maslinic acid and oleanolic acid. This study has applauded oleic acid, linoleic acid and tyrosol as olive oil bioactive constituents that have several potential pharmacological effects in humans that modulate several enzymes, receptors and transcription factors. The future work will be to investigate the effects of oleic acid on fatty acid-binding proteins and telomerase reverse transcriptase; melatonin on quinone reductase 2; tyrosol on carbonic anhydrase II; maslinic acid and oleanolic acid on protein-tyrosine phosphatase 1B

In Silico Evaluation of the Antioxidant, Anti-Inflammatory, and Dermatocosmetic Activities of Phytoconstituents in Licorice (<i>Glycyrrhiza glabra</i> L.)

The global demand for herbal cosmetics is vastly increasing due to their health benefits and relative safety. Glycyrrhiza spp. extracts are used in cosmetic preparations due to their skin-whitening, antisensitizing, and anti-inflammatory properties. The aim of this work is to computationally evaluate the bioactive constituents of licorice (Glycyrrhiza glabra L.) that possess antioxidant, anti-inflammatory, and dermatocosmetic activities, and elucidate the dynamics of their molecular targets. The used methods are skin permeability prediction, target prediction, molecular docking, and molecular dynamic simulation (MDS). The results show that, at a skin permeation cut-off value of −6.0 cm/s, nine phytoconstituents of licorice (furfuraldehyde, glucoliquiritin apioside, glycyrrhizin, isoliquiritin, licopyranocoumarin, licuraside, liquiritigenin, liquiritin, and liquiritin apioside) were workable. Molecular target prediction results indicate probability for tyrosinase, 11-beta-hydroxysteroid dehydrogenase 1 (HSD11B1), monoamine oxidase B, steroid 5-alpha-reductase 1, and cyclo-oxygenase-1. On the basis of molecular docking, glucoliquiritin apioside and glycyrrhizin had the best antioxidant, anti-inflammation, and dermatocosmetic activities. MDS results show that the complexes had good stability, and MMGBSA results indicate that the complexes had satisfactory binding energy. Overall, this study demonstrates that licorice extracts are potential antioxidants that could enhance histological dermal and epidermal properties, and reduce the level of inflammatory and wrinkling markers

In Silico Investigation of First-Pass Effect on Selected Small Molecule Excipients and Structural Dynamics of P-glycoprotein

In this study, the interaction of selected pharmaceutical excipients on the function of P-glycoprotein (P-gp) and activity of 6 cytochrome P450 (CYP) isoforms were computationally investigated. At binding free energy cut-off value of −5.0 kcal/mol, the result showed possible modulatory or inhibitory effect by cethyl alcohol on CPY3A4 and P-gp; cetyltrimethyl-ammonium bromide (CTAB) on CYP1A2 and P-gp; dibutyl sebacate on CYP2C9, CYP2E1, and P-gp; sodium caprylate on CYP1A2 and CYP3A4; while most of the tested excipients have good interaction with the cytochromes and P-gp. The predicted pharmacokinetics provided possible inhibitors of the CYPs and P-gp and suggested that aspartame and acetyl tributyl citrate may not permeate blood–brain barrier and not act as P-gp substrates. Target prediction for CTAB showed 100% and 35% probability of target to dynamin-1 (UniProt ID: Q05193) and histamine H3 receptor (UniProt ID: Q9Y5N1), respectively, whereas tricaprylin showed 40% probability of target to 5 Protein kinase C (UniProt IDs: P17252, Q02156, Q04759, P24723, and P05129). This study shows that synergistic effect of some excipients present in a drug formulation and multiple drugs administration is possible through modulation of CYPs activities and P-gp function, and this is crucial for consideration to mitigate toxicity in pediatric and adult populations

In silico assessment of Hibiscus sabdariffa as a possible therapeutic agent for breast cancer management

Breast cancer remains the most frequently diagnosed cancer worldwide. Several drugs have been identified and found to be active against the pathogenesis of breast cancer, however, the uniqueness each tumor cell exhibit remains a major issue. The difference in the phenotypes of tumor cells and the high metastatic activity they exhibit have heightened the incurability of breast cancer. It is completely necessary to continue to discover potentially active molecular species that can effectively treat all breast cancer types. To this end, this study employs a biomolecular simulation protocol to screen the compounds of Hibiscus sabdariffa and identify compounds that can bind to and potentially inhibit the activities of selected target enzymes and receptors. Using a molecular docking approach, several compounds were identified in each protein category and reported herein. The top five compounds had docking scores ranging from −9.52 to −11.79 kcal mol−1 on Human Epidermal Growth Factor Receptor 2 (HER2), −11.09 to −13.63 kcal mol−1 on Epidermal Growth Factor Receptor (EGFR), −11.07 to −14.03 kcal mol−1 on Progesterone receptor (PR), −11.53 to −14.71 on Phosphatidylinositol 3-kinase (PI3K) and −8.16 to −9.31 on Estrogen receptor (ER). Subsequently, MM/GBSA protocol was employed to rescore the docked complexes and calculate the binding energy. Further ADMET screening on the top-scoring compounds returned good pharmacokinetic behaviors. Conclusively, the results showed that these compounds could be explored as natural alternatives to available drugs, however, validatory tests are recommended