Anti-Periodontopathogenic Ability of Mangrove Leaves (Aegiceras corniculatum) Ethanol Extract: In silico and in vitro study.

OBJECTIVE: Mangrove (Aegiceras corniculatum) is an abundant natural marine resource of Indonesia, which can be explored for treating periodontal disease due to its potential as immunoregulatory, antibacterial, and antioxidant properties. The objective of this study was to investigate the active compound from Indonesian mangrove leaf extract (A. corniculatum) (MLE) for developing a herbal-based mouthwash through in silico and in vitro studies. MATERIALS AND METHODS: Phytochemistry and liquid chromatography-high resolution mass spectrometry (LC-HRMS) were done to explore the active compounds in MLE. Chemistry screening and interaction, absorption, distribution, metabolism, and excretion (ADME), molecular docking simulation, and visualization of MLE active compounds as anti-inflammatory, antioxidant, and antibacterial were investigated in silico The inhibition zone of MLE against Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), and Fusobacterium nucleatum (Fn) as periodontopathogenic bacterias was performed by diffusion method. Doxycycline 100 mg was used as a positive control, as a treatment group, there were five groups, namely 0%, 25%, 50%, 75%, and 100% MLE. RESULTS: Alkaloid, saponin, flavonoid, triterpenoid, steroid, tannin, and quinone were detected in MLE. A high concentration of (-)epicatechin and coumaric acid (CA) were found in MLE. MLE in 100% concentration has the most effective ability to inhibit Fn, Pg, Aa growth in vitro. (-)-Epicatechin has a higher negative binding affinity than CA that can enhance heat shock protein (HSP)-30, HSP-70, HSP-90, interleukin-10, and FOXP3 and also inhibit interleukin-6, peptidoglycan, flagellin, and dectin in silico. CONCLUSION: MLE of A. corniculatum has antioxidant, anti-inflammatory, and antibacterial activities that can be a potential raw material for developing a herbal-based mouthwash.

Anti-Peri-implantitis Bacteria's Ability of Robusta Green Coffee Bean (Coffea Canephora) Ethanol Extract: An In Silico and In Vitro Study.

OBJECTIVE: This study was aimed to investigate RGCBE extract as antioxidant and anti-peri-implantitis bacteria through in vitro study and its potential as antioxidant, antibacterial, anti-inflammatory, antibone resorption, and proosteogenic through in silico study. MATERIALS: AND METHODS: Absorption, distribution, metabolism, excretion and toxicity prediction, molecular docking simulation, and visualization of chlorogenic acid (CGA) and coumaric acid (CA) as anti-inflammatory, antioxidant, and antibacterial were investigated in silico. Inhibition zone by diffusion method, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) of RGCBE extract against Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Fusobacterium nucleatum (Fn), and Prevotella intermedia (Pi) were done. STATISTICAL ANALYSIS: the analysis of variance (ANOVA) difference test, and the post-hoc Tukey's Honest Significant Different (HSD) with a different significance value of p<0.05 RESULTS: GCA and CA compounds are good drug molecules and it has low toxicity. Chlorogenic acid have higher binding activity than coumaric acid to tumor necrosis factor (TNF)-α, nuclear factor (NF)-κB, receptor activation NF-κB (RANK) and its ligand (RANKL), interleukin (IL)-6, IL-10, runt related transcription factor (RUNX2), receptor activator nuclear Kappa beta Ligand-osteoprotegrin osteocalcin (RANKL-OPG), osteocalcin, nuclear factor associated T-cell 1 (NFATc1), tartate resistant acid phosphatase (TRAP), peptidoglycan, flagellin, dectin, Hsp70, and Hsp10 protein. RGCB ethanol extract has high antioxidant ability and it has MIC, MBC, and inhibit the growth of Aa, Pg, Fn, and Pi at 50% concentration with significantly different (p=0.0001 and<0.05). CONCLUSION: RGCB ethanol extract has high antioxidant ability and 50% RGCB ethanol extract may act as strong anti-peri-implantitis bacteria in vitro. In addition, CGA in RGCB potential as antioxidant, antibacterial, anti-inflammatory, antibone resorption, and proosteogenic in silico.

Molecular docking and dynamic simulation of conserved B cell epitope of SARS-CoV-2 glycoprotein Indonesian isolates: an immunoinformatic approach.

Background: An immunoinformatic approach may be useful to investigate the conserved region in the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Indonesia isolates. The aim of this study was to investigate Indonesian SARS-CoV-2 isolates based on B cell epitopes by targeting the conserved regions in the spike glycoprotein to trigger increased multi-variant virus neutralization and memory response for the development of vaccine seed candidates. Methods: SARS-CoV-2 spike glycoprotein gene sequences originating from Indonesia were compared with Wuhan (China), the United Kingdom, South Africa, India, the United States, and Brazil isolates obtained from the NCBI and GISAID databases. The recognition of antigens was carried out directly using B cells through the B cell receptor (BCR). An indirect B cell activation by Cluster of Differentiation (CD)4+ T cells and major histocompatibility complex (MHC)-II was predicted through the binding with human leukocyte antigen (HLA) based on IC 50 value. In addition, vaccine allergenicity and toxicity were investigated. During the molecular complex examination, the 3D peptide structure was investigated and the lowest amount of energy formed when the vaccine candidate peptide bound to BCR and MHC-II was calculated. Results: As a result, the spike glycoprotein sequences of Indonesian SARS-CoV-2 isolates had conserved regions which were very similar to reference countries such as China, the United Kingdom, South Africa, India, the United States, and Brazil. Conclusion: It was predicted that the conserved regions could be identified as the epitope of B and T CD4+ cells that produced the peptides for vaccine candidate with antigenic, non-allergen, and non-toxic properties.

Molecular docking of anthocyanins and ternatin in Clitoria ternatea as coronavirus disease oral manifestation therapy.

Herbal active compound with immunoregulator ability is considered a potential therapy for COVID-19 oral manifestation by downregulating pro-inflammatory cytokine storm. Meanwhile, anthocyanin and ternatin are the active compounds in Clitoria ternatea, which may act as a potential immunoregulator for COVID-19 therapy. The intention of this investigation was to investigate anthocyanin and ternatin as active compounds in C. ternatea that may be able to increase anti-inflammatory cytokine and inhibit pro-inflammatory cytokine and key proteins of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This study implemented bioinformatic approach to analyze anthocyanin and ternatin as active compounds in C. ternatea with anti- and pro-inflammatory cytokines and antiviral examination history through blind molecular docking study (in silico). Moreover, anthocyanins and ternatin were obtained from PubChem database by minimizing ligand structure in PyRx software to increase the flexibility. RCSB database was employed for preparing the protein samples consisting of interleukin (IL)-6, SARS-CoV-2-ACE2 glycoprotein complex, tumor necrosis factor-α receptor (TNF-αR), matrix metalloproteinase-9 (MMP-9), IL-6, IL-10, and human beta defensin-2 (HBD-2). In addition, The PyMol sofware was used to sterilize the protein samples to obtain the molecular docking optimization. This investigation found that, in the molecular docking simulation, the anthocyanin and ternatin showed producing the negative binding affinity to the ACE2 domain which interacted with RBD glycoprotein SARS-CoV-2. Anthocyanin and ternatin were then predicted to be able to influence any inhibitory activity of TNF-αR, MMP-9, and IL-6; increase IL-10; and increase HBD2 binding affinity values negatively. It can be predicted through molecular docking that anthocyanin and ternatin as the active compounds in C. ternatea contribute as a potential agent for COVID-19 oral manifestation therapy.

Retrieval and Investigation of Data on SARS-CoV-2 and COVID-19 Using Bioinformatics Approach.

Sudden emergence and a rapid outbreak of SARS-CoV-2 accompanied by a devastating impact on the economy and public health has driven extensive scientific mobilization to study and elucidate the various associated concerns about SARS-CoV-2. Bioinformatics plays a crucial role in addressing and providing solutions to questions about SARS-CoV-2. It helps shorten the duration for the vaccine development process and the discovery of potential clinical interventions through the simulation and information retrieval, and the development of well-ordered information hubs and resources, which are essential to derive data and meaningful findings from the current massive information about SARS-CoV-2. Advanced algorithms in this field also provide approaches that are essential to elucidate the relationship, origin, and evolutionary process of SARS-CoV-2. Here, we report essential bioinformatics entities, such as database and platform development, molecular evolution and phylogenetic analyses, and vaccine designs, that are useful to solve the SARS-CoV-2 conundrum.

In Silico and in Vitro Study of Trace Amines (TA) and Dopamine (DOP) Interaction with Human Alpha 1-Adrenergic Receptor and the Bacterial Adrenergic Receptor QseC.

BACKGROUND/AIMS: Trace amines (TA) are small organic compounds that have neuromodulator activity due to their interaction with some neuron-related receptors, such as trace amine associated receptors (TAARs), α2-adrenergic receptor (α2-AR) and ß-adrenergic receptor (ß-AR). However, there is little information on whether TA and dopamine (DOP) can interact with other adrenergic receptors (ARs) such as the mammalian α1-AR and the bacterial counterpart QseC, which is involved in quorum sensing of some Gram-negative pathogens. The aim of this study was to investigate the interaction of TA and DOP with α1-AR and QseC. METHODS: We performed an in silico study using 3D structure from SWISS MODEL and analyzed the protein interaction via molecular docking using PyMol, PoseView and PyRX 8.0. For the in vitro study, we investigated the QseC kinase activity by measuring the remaining ATP in a reaction containing QseC-enriched membrane incubated together with purified QseB and EPI, TA, DOP, or PTL respectively. We also measured the intracellular Ca++ levels, which represents the α1-AR activation, in LNCAP (pancreatic cell line) cells treated with EPI, TA, DOP and PTL respectively using a fluorescence-based assay. The LNCAP cell proliferation was measured using an MTT-based assay. RESULTS: Our in silico analysis revealed that TAs and DOP have high binding affinity to the human α1-AR and the bacterial adrenergic receptor (QseC), comparable to epinephrine (EPI). Both are membrane-bound kinases. Experimental studies with pancreatic cell line (LNCAP) showed that the TAs and DOP act as α1-AR antagonist by counteracting the effect of EPI. In the presence of EPI, TA and DOP trigger an increase of the intracellular Ca++ levels in the LNCAP cells leading to an inhibition of cell proliferation. Although in silico data suggest an interaction of TA and DOP with QseC, they do not inhibit the kinase activity of QseC, a histidine kinase receptor involved in quorum sensing which is also sensitive to EPI. CONCLUSION: Our study showed that the TAs and DOP act as α1-AR antagonist but no effect was observed for QseC.