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Due to their life cycle, viruses can disrupt the metabolism of their hosts, causing diseases. If we want to disrupt their life cycle, it is necessary to identify their presence. For this purpose, it is possible to use several molecular-biological and bioanalytical methods. The reference selection was performed based on electronic databases (2020-2023). This review focused on electrochemical methods with high sensitivity and selectivity (53% voltammetry/amperometry, 33% impedance, and 12% other methods) which showed their great potential for detecting various viruses. Moreover, the aforementioned electrochemical methods have considerable potential to be applicable for care-point use as they are portable due to their miniaturizability and fast speed analysis (minutes to hours), and are relatively easy to interpret. A total of 2011 articles were found, of which 86 original papers were subsequently evaluated (the majority of which are focused on human pathogens, whereas articles dealing with plant pathogens are in the minority). Thirty-two species of viruses were included in the evaluation. It was found that most of the examined research studies (77%) used nanotechnological modifications. Other ones performed immunological (52%) or genetic analyses (43%) for virus detection. 5% of the reports used peptides to increase the method's sensitivity. When evaluable, 65% of the research studies had LOD values in the order of ng or nM. The vast majority (79%) of the studies represent proof of concept and possibilities with low application potential and a high need of further research experimental work.

Genes associated with drug resistance of first line drugs for Plasmodium falciparum have been identified and characterized of which three genes most commonly associated with drug resistance are P. falciparum chloroquine resistance transporter gene ( PfCRT ), P. falciparum multidrug drug resistance gene 1 ( PfMDR1 ), and P. falciparum Kelch protein K13 gene ( PfKelch13 ). Polymorphism in these genes could be used as molecular markers for identifying drug resistant strains. Nucleic acid amplification test (NAAT) along with DNA sequencing is a powerful diagnostic tool that could identify these polymorphisms. However, current NAAT and DNA sequencing technologies require specific instruments which might limit its application in rural areas. More recently, a combination of isothermal amplification and CRISPR detection system showed promising results in detecting mutations at a nucleic acid level. Moreover, the Loop-mediated isothermal amplification (LAMP)-CRISPR systems offer robust and straightforward detection, enabling it to be deployed in rural and remote areas. The aim of this study was to develop a novel diagnostic method, based on LAMP of targeted genes, that would enable the identification of drug-resistant P. falciparum strains. The methods were centered on sequence analysis of P. falciparum genome, LAMP primers design, and CRISPR target prediction. Our designed primers are satisfactory for identifying polymorphism associated with drug resistant in PfCRT, PfMDR1, and PfKelch13 . Overall, the developed system is promising to be used as a detection method for P. falciparum treatment-resistant strains. However, optimization and further validation the developed CRISPR-LAMP assay are needed to ensure its accuracy, reliability, and feasibility., Competing Interests: Authors declare no conflict of interest in any capacity, including competing or financial., (© 2023 The Author(s).)

Resistance to anti-tuberculosis drugs, especially ethambutol (EMB), has been widely reported worldwide. EMB resistance is caused by mutations in the embB gene, which encodes the arabinosyl transferase enzyme. This study aimed to detect mutations in the embB gene of Mycobacterium tuberculosis from Papua and to evaluate their impact on the effectiveness of EMB. We analyzed 20 samples of M. tuberculosis culture that had undergone whole-genome sequencing, of which 19 samples were of sufficient quality for further bioinformatics analysis. Mutation analysis was performed using TBProfiler, which identified M306L, M306V, D1024N, and E378A mutations. In sample TB035, the M306L mutation was present along with E378A. The binding affinity of EMB to arabinosyl transferase was calculated using AutoDock Vina. The molecular docking results revealed that all mutants demonstrated an increased binding affinity to EMB compared to the native protein (-0.948 kcal/mol). The presence of the M306L mutation, when coexisting with E378A, resulted in a slight increase in binding affinity compared to the M306L mutation alone. The molecular dynamics simulation results indicated that the M306L, M306L + E378A, M306V, and E378A mutants decreased protein stability. Conversely, the D1024N mutant exhibited stability comparable to the native protein. In conclusion, this study suggests that the M306L, M306L + E378A, M306V, and E378A mutations may contribute to EMB resistance, while the D1024N mutation may be consistent with continued susceptibility to EMB.

CRISPR-Cas9 has emerged as a revolutionary tool that enables precise and efficient modifications of the genetic material. This review provides a comprehensive overview of CRISPR-Cas9 technology and its applications in genome editing. We begin by describing the fundamental principles of CRISPR-Cas9 technology, explaining how the system utilizes a single guide RNA (sgRNA) to direct the Cas9 nuclease to specific DNA sequences in the genome, resulting in targeted double-stranded breaks. In this review, we provide in-depth explorations of CRISPR-Cas9 technology and its applications in agriculture, medicine, environmental sciences, fisheries, nanotechnology, bioinformatics, and biotechnology. We also highlight its potential, ongoing research, and the ethical considerations and controversies surrounding its use. This review might contribute to the understanding of CRISPR-Cas9 technology and its implications in various fields, paving the way for future developments and responsible applications of this transformative technology., Competing Interests: All the authors declare that there are no conflicts of interest., (© 2023 The Author(s).)

Reports on T-cell cross-reactivity against SARS-CoV-2 epitopes in unexposed individuals have been linked with prior exposure to the human common cold coronaviruses (HCCCs). Several studies suggested that cross-reactive T-cells response to live attenuated vaccines (LAVs) such as BCG (Bacillus Calmette-Guérin), OPV (Oral Polio Vaccine), and MMR (measles, mumps, and rubella) can limit the development and severity of COVID-19. This study aims to identify potential cross-reactivity between SARS-CoV-2, HCCCs, and LAVs in the context of T-cell epitopes peptides presented by HLA (Human Leukocyte Antigen) alleles of the Indonesian population. SARS-CoV-2 derived T-cell epitopes were predicted using immunoinformatics tools and assessed for their conservancy, variability, and population coverage. Two fully conserved epitopes with 100% similarity and nine heterologous epitopes with identical T-cell receptor (TCR) contact residues were identified from the ORF1ab fragment of SARS-CoV-2 and all HCCCs. Cross-reactive epitopes from various proteins of SARS-CoV-2 and LAVs were also identified (15 epitopes from BCG, 7 epitopes from MMR, but none from OPV). A majority of the identified epitopes were observed to belong to ORF1ab, further suggesting the vital role of ORF1ab in the coronaviruses family and suggesting it as a candidate for a potential universal coronavirus vaccine that protects against severe disease by inducing cell mediated immunity.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a newly emerging virus well known as the major cause of the worldwide pandemic due to Coronavirus Disease 2019 (COVID-19). Major breakthroughs in the Next Generation Sequencing (NGS) field were elucidated following the first release of a full-length SARS-CoV-2 genome on the 10 January 2020, with the hope of turning the table against the worsening pandemic situation. Previous studies in respiratory virus characterization require mapping of raw sequences to the human genome in the downstream bioinformatics pipeline as part of metagenomic principles. Illumina, as the major player in the NGS arena, took action by releasing guidelines for improved enrichment kits called the Respiratory Virus Oligo Panel (RVOP) based on a hybridization capture method capable of capturing targeted respiratory viruses, including SARS-CoV-2; therefore, allowing a direct map of raw sequences data to SARS-CoV-2 genome in downstream bioinformatics pipeline. Consequently, two bioinformatics pipelines emerged with no previous studies benchmarking the pipelines. This study focuses on gaining insight and understanding of target enrichment workflow by Illumina through the utilization of different bioinformatics pipelines named as 'Fast Pipeline' and 'Normal Pipeline' to SARS-CoV-2 strains isolated from Yogyakarta and Central Java, Indonesia. Overall, both pipelines work well in the characterization of SARS-CoV-2 samples, including in the identification of major studied nucleotide substitutions and amino acid mutations. A higher number of reads mapped to the SARS-CoV-2 genome in Fast Pipeline and merely were discovered as a contributing factor in a higher number of coverage depth and identified variations (SNPs, insertion, and deletion). Fast Pipeline ultimately works well in a situation where time is a critical factor. On the other hand, Normal Pipeline would require a longer time as it mapped reads to the human genome. Certain limitations were identified in terms of pipeline algorithm, whereas it is highly recommended in future studies to design a pipeline in an integrated framework, for instance, by using NextFlow, a workflow framework to combine all scripts into one fully integrated pipeline., Competing Interests: The authors declare no conflict of interest.

One approach for solving the problem of antibiotic resistance and bacterial persistence in biofilms is treatment with metals, including silver in the form of silver nanoparticles (AgNPs). Green synthesis is an environmentally friendly method to synthesize nanoparticles with a broad spectrum of unique properties that depend on the plant extracts used. AgNPs with antibacterial and antibiofilm effects were obtained using green synthesis from plant extracts of Lagerstroemia indica (AgNPs_LI), Alstonia scholaris (AgNPs_AS), and Aglaonema multifolium (AgNPs_AM). Nanoparticles were characterized by transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDX) analysis. The ability to quench free radicals and total phenolic content in solution were also evaluated. The antibacterial activity of AgNPs was studied by growth curves as well as using a diffusion test on agar medium plates to determine minimal inhibitory concentrations (MICs). The effect of AgNPs on bacterial biofilms was evaluated by crystal violet (CV) staining. Average minimum inhibitory concentrations of AgNPs_LI, AgNPs_AS, AgNPs_AM were 15 ± 5, 20 + 5, 20 + 5 μg/mL and 20 ± 5, 15 + 5, 15 + 5 μg/mL against Gram-positive ( Staphylococcus aureus ) and Gram-negative ( Escherichia coli ) bacteria, respectively. The E. coli strain formed biofilms in the presence of AgNPs, a less dense biofilm than the S. aureus strain. The highest inhibitory and destructive effect on biofilms was exhibited by AgNPs prepared using an extract from L. indica .

Background: Tuberculosis is one of the deadliest disease caused by Mycobacterium tuberculosis. Its treatment still becomes a burden for many countries including Indonesia. Drug resistance is one of the problems in TB treatment. However, a development in the molecular field through Whole-genome sequencing (WGS) can be used as a solution in detecting mutations associated with TB- drugs. This investigation intended to implement this data for supporting the scientific community in deeply understanding any TB epidemiology and evolution in Papua along with detecting any mutations in genes associated with TB-Drugs., Result: A whole-genome sequencing was performed on the random samples from TB Referral Laboratory in Papua utilizing MiSeq 600 cycle Reagent Kit (V3). Furthermore, TBProfiler was used for genome analysis, RAST Server was employed for annotation, while Gview server was applied for BLAST genome mapping and a Microscope server was implemented for Regions of Genomic Plasticity (RGP). The largest genome of M. tuberculosis obtained was at the size of 4,396,040 bp with subsystems number at 309 and the number of coding sequences at 4326. One sample (TB751) contained one RGP. The drug resistance analysis revealed that several mutations associated with TB-drug resistance existed. In details, mutations of rpoB gene which were identified as S450L, D435Y, H445Y, L430P, and Q432K had caused the reduced effectiveness of rifampicin; while the mutases in katG (S315T), kasA (312S), inhA (I21V), and Rv1482c-fabG1 (C-15 T) genes had contributed to the resistance in isoniazid. In streptomycin, the resistance was triggered by the mutations in rpsL (K43R) and rrs (A514C, A514T) genes, and, in Amikacin, its resistance was led by mutations in rrs (A514C) gene. Additionally, in Ethambutol and Pyrazinamide, their reduced effectiveness was provoked by embB gene mutases (M306L, M306V, D1024N) and pncA (W119R)., Conclusions: The results from whole-genome sequencing of TB clinical sample in Papua, Indonesia could contribute to the surveillance of TB-drug resistance. In the drug resistance profile, there were 15 Multi Drugs Resistance (MDR) samples. However, Extensively Drug-resistant (XDR) samples have not been found, but samples were resistant to only Amikacin, a second-line drug., (© 2021. The Author(s).)

Diabetes remains one of the most prevalent non-communicable diseases in the world, affecting over 400 million of people worldwide, causing serious complications leading to amputations and even death. Over the years, researchers have found that, in addition to genomic mutations, epigenetic mechanisms also play a role in the development of diabetes-specifically type-2 diabetes. Long noncoding RNAs (lncRNAs) have been linked to mediate epigenetic mechanisms, including those in late-stage diabetes. This study attempts to assess the unexplored topic of how lncRNAs could be used to assess the epigenetic mechanisms present in diabetic peripheral neuropathy (DPN); a serious complication of the disease often leading to amputation. Differential lncRNA expression analysis was done with a dataset containing DPN and healthy patients. Standard and corrected t test, and also LIMMA was applied. Results of this study indicates the usefulness of lncRNAs as an exploratory tool to elucidate the complexity of the epigenetic mechanisms of human DPN.

The menace of cervical cancer has reached an alarming rate. There are more than 450.000 cases of cervical cancer yearly, with mortality rate of about 50%. This deadly cancer is caused by human papillomavirus (HPV), mainly subtypes 16 and 18. The pharmaceutical industry has produced drug for combating the virus, known as SAHA (suberoylanilide hydroxamic acid). It inhibits class II HDAC Homo sapiens (HDACi). The utilization of SAHA has some side effects, one of which is bone loss. Thus, searching for viable alternatives aside SAHA is inevitable. The objective of this research is to investigate the molecular interaction of selected Indonesian natural products with class II HDAC Homo sapiens. LigX tool in MOE 2008.10 was used as an instrument to investigate the molecular interaction . Then, computer-aided drug discovery and development (CADDD) approach involving molecular docking and dynamics methods was utilized to screen the natural products library. In the end, we found that herbaric acid could act as a potential drug candidate for cervical cancer.

Ebola Hemorrhagic Fever (EHF) is a disease caused by viruses from genus Ebolavirus. Zaire ebolavirus (EBOV) is the deadliest species which has 76% case fatality rate. Up until now, there is no U.S. Food and Drug Administration (FDA) approved drugs to treat EHF. Antiviral drug based on EBOV N-terminal heptad repeat glycoprotein-2 (NHR GP2) Ectodomain inhibitor is one kind of treatment that has not well developed. NHR GP2 Ectodomain has an important role in the process of EBOV entry into the cell through endocytosis mechanism. In this study, we used in silico methods to investigate the activity of commercial cyclic peptide conjugated to Human Immunodeficiency Virus type 1 Trans-activator of the transcription (HIV-1 Tat) peptide as ligands which act as an inhibitor of EBOV NHR GP2 Ectodomain. The commercial cyclic peptides which we used in this study were obtained from the selected chemical companies. Conjugation of the commercial cyclic peptides to HIV-1 Tat peptide was done in order to accumulate it inside the endosome. The ligands which had the best inhibition properties were screened using molecular docking and molecular dynamics simulation. Prediction of pharmacological properties of the peptides was done to choose the best drug candidate. The result of screening processes shows that Ligand 023 has the highest potency as the drug lead. The ligand needs to undergo further analysis through in vitro, in vivo, and a clinical trial to ensure that this ligand has a therapeutic ability as an antiviral drug for Ebola virus infection., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Dengue fever is still a major threat worldwide, approximately threatening two-fifths of the world's population in tropical and subtropical countries. Nonstructural protein 5 (NS5) methyltransferase enzyme plays a vital role in the process of messenger RNA capping of dengue by transferring methyl groups from S -adenosyl-l-methionine to N7 atom of the guanine bases of RNA and the RNA ribose group of 2'OH, resulting in S -adenosyl-l-homocysteine (SAH). The modification of SAH compound was screened using molecular docking and molecular dynamics simulation, along with computational ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity) test. The 2 simulations were performed using Molecular Operating Environment (MOE) 2008.10 software, whereas the ADME-Tox test was performed using various software. The modification of SAH compound was done using several functional groups that possess different polarities and properties, resulting in 3460 ligands to be docked. After conducting docking simulation, we earned 3 best ligands (SAH-M331, SAH-M2696, and SAH-M1356) based on ΔG binding and molecular interactions, which show better results than the standard ligands. Moreover, the results of molecular dynamics simulation show that the best ligands are still able to maintain the active site residue interaction with the binding site until the end of the simulation. After a series of molecular docking and molecular dynamics simulation were performed, we concluded that SAH-M1356 ligand is the most potential SAH-based compound to inhibit NS5 methyltransferase enzyme for treating dengue fever., Competing Interests: DECLARATION OF CONFLICTING INTERESTS: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Meningitis infection is one of the major threats during Hajj season in Mecca. Meningitis vaccines are available, but their uses are limited in some countries due to religious reasons. Furthermore, they only give protection to certain serogroups, not to all types of meningitis-inducing bacteria. Recently, research on epitope-based vaccines has been developed intensively. Such vaccines have potential advantages over conventional vaccines in that they are safer to use and well responded to the antibody. In this study, we developed epitope-based vaccine candidates against various meningitis-inducing bacteria, including Streptococcus pneumoniae , Neisseria meningitidis , and Haemophilus influenzae type b. The epitopes were selected from their protein of polysaccharide capsule. B-cell epitopes were predicted by using BCPred, while T-cell epitope for major histocompatibility complex (MHC) class I was predicted using PAProC, TAPPred, and Immune Epitope Database. Immune Epitope Database was also used to predict T-cell epitope for MHC class II. Population coverage and molecular docking simulation were predicted against previously generated epitope vaccine candidates. The best candidates for MHC class I- and class II-restricted T-cell epitopes were MQYGDKTTF, MKEQNTLEI, ECTEGEPDY, DLSIVVPIY, YPMAMMWRNASNRAI, TLQMTLLGIVPNLNK, ETSLHHIPGISNYFI, and SLLYILEKNAEMEFD, which showed 80% population coverage. The complexes of class I T-cell epitopes-HLA-C*03:03 and class II T-cell epitopes-HLA-DRB1*11:01 showed better affinity than standards as evaluated from their Δ G binding value and the binding interaction between epitopes and HLA molecules. These peptide constructs may further be undergone in vitro and in vivo testings for the development of targeted vaccine against meningitis infection., Competing Interests: Authors disclose no potential conflicts of interest.

From 2003 to 2013, Indonesia had the highest number of avian influenza A cases in humans, with 192 cases and 160 fatalities. Avian influenza is caused by influenza virus type A, such as subtype H5N1. This virus has two glycoproteins: hemagglutinin and neuraminidase, which will become the primary target to be neutralized by vaccine. Vaccine is the most effective immunologic intervention. In this study, we use the epitope-based vaccine design from hemagglutinin and neuraminidase of H5N1 Indonesian strain virus by using immunoinformatics approach in order to predict the binding of B-cell and T-cell epitopes (class I and class II human leukocyte antigen [HLA]). BCPREDS was used to predict the B-cell epitope. Propred, Propred I, netMHCpan, and netMHCIIpan were used to predict the T-cell epitope. Two B-cell epitopes of hemagglutinin candidates and one B-cell epitope of neuraminidase candidates were obtained to bind T-cell CD4(+) (class II HLA), and also five T-cell epitope hemagglutinin and four T-cell epitope neuraminidase were obtained to bind T-cell CD8(+) (class I HLA). The visualization of epitopes was done using MOE 2008.10. It shows that the binding affinity of epitope-HLA was based on minimum binding free energy (ΔG binding). Based on this result, visualization, and dynamic simulation, four hemagglutinin epitopes (MEKIVLLLA, CPYLGSPSF, KCQTPMGAI, and IGTSTLNQR) and two neuraminidase epitopes (NPNQKIITI and CYPDAGEIT) were computed as having the best binding affinity from HLA ligand. The results mentioned above are from in silico experiments and need to be validated using wet experiment.

Dengue is an infectious disease caused by dengue virus (DENV) and transmitted between human hosts by mosquitoes. Recently, Indonesia was listed as a country with the highest cases of dengue by the Association of Southeast Asian Nations. The current treatment for dengue disease is supportive therapy; there is no antiviral drug available in the market against dengue. Therefore, a research on antiviral drug against dengue is very important, especially to prevent outbreak explosion. In this research, the development of dengue antiviral is performed through the inhibition of n-octyl-β-D-glucoside (β-OG) binding pocket on envelope protein of DENV by using analogs of β-OG pocket binder. There are 828 compounds used in this study, and all of them were screened based on the analysis of molecular docking, pharmacological character prediction of the compounds, and molecular dynamics simulation. The result of these analyses revealed that the compound that can be used as an antiviral candidate against DENV is 5-(3,4-dichlorophenyl)-N-[2-(p-tolyl) benzotriazol-5-yl]furan-2-carboxamide.

This research focused on the modification of the functional groups of oseltamivir as neuraminidase inhibitor against influenza A virus subtype H1N1. Interactions of three of the best ligands were evaluated in the hydrated state using molecular dynamics simulation at two different temperatures. The docking result showed that AD3BF2D ligand (N-[(1S,6R)-5-amino-5-{[(2R,3S,4S)-3,4-dihydroxy-4-(hydroxymethyl) tetrahydrofuran-2-yl]oxy}-4-formylcyclohex-3-en-1-yl]acetamide-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate) had better binding energy values than standard oseltamivir. AD3BF2D had several interactions, including hydrogen bonds, with the residues in the catalytic site of neuraminidase as identified by molecular dynamics simulation. The results showed that AD3BF2D ligand can be used as a good candidate for neuraminidase inhibitor to cope with influenza A virus subtype H1N1.

It is critical to seek potential alternative treatments for H1N1 infections by inhibiting neuraminidase-1 enzyme. One of the viable options for inhibiting the activity of neuraminidase- 1 is peptide drug design. In order to increase peptide stability, cyclization is necessary to prevent its digestion by protease enzyme. Cyclization of peptide ligands by formation of disulfide bridges is preferable for designing inhibitors of neuraminidase-1 because of their high activity and specificity. Here we designed ligands by using molecular docking, drug scan and dynamics computational methods. Based on our docking results, short polypeptides of cystein-arginine-methionine-tyrosine- -proline-cysteine (CRMYPC) and cysteine-arginine-aspargine- phenylalanine-proline-cysteine (CRNFPC) have good residual interactions with the target and the binding energy ΔGbinding of -31.7402 and -31.0144 kcal mol-1, respectively. These values are much lower than those of the standards, and it means that both ligands are more accessible to ligand-receptor binding. Based on drug scan results, both of these ligands are neither mutagenic nor carcinogenic. They also show good oral bioavailability. Moreover, both ligands show relatively stable molecular dynamics progression of RMSD vs. time plot. However, based on our metods, the CRMYPC ligand has sufficient hydrogen bonding interactions with residues of the active side of neuraminidase-1 and can be therefore proposed as a potential inhibitor of neuraminidase-1.

Dengue has become a major global health threat, especially in tropical and subtropical regions. The development of antiviral agent targeting viral replication is really needed at this time. NS5 methyltransferase presents as a novel antiviral target. This enzyme plays an important role in the methylation of 5'-cap mRNA. Inhibition of the NS5 methyltransferase could inhibit dengue virus replication. In this research, two sites of NS5 methyltransferase (S-Adenosyl methionine/SAM binding site and RNA-cap site) were used as targets for inhibition. As much as 300 commercial cyclic peptides were screened to these target sites by means of molecular docking. Analysis of ligand-enzyme binding free energy and pharmacological prediction revealed two best ligands, namely [Tyr123] Prepro Endothelin (110-130), amide, human and Urotensin II, human. According to molecular dynamic simulation, both ligands maintain a stable complex conformation between enzyme and ligand at temperature 310 K and 312 K. Hence, Urotensin II, human is more reactive at 312 K than at 310 K. However, both ligands can be used as potential inhibitor candidates against NS5 methyltransferase of dengue virus with Urotensin II, human exposes more promising activity at 312 K.

Histone deacetylase (HDAC) has a critical function in regulating gene expression. The inhibition of HDAC has developed as an interesting anticancer research area that targets biological processes such as cell cycle, apoptosis, and cell differentiation. In this study, an HDAC inhibitor that is available commercially, suberoyl anilide hydroxamic acid (SAHA), has been modified to improve its efficacy and reduce the side effects of the compound. Hydrophobic cap and zinc-binding group of these compounds were substituted with boron-based compounds, whereas the linker region was substituted with p-aminobenzoic acid. The molecular docking analysis resulted in 8 ligands with ΔG binding value more negative than the standards, SAHA and trichostatin A (TSA). That ligands were analyzed based on the nature of QSAR, pharmacological properties, and ADME-Tox. It is conducted to obtain a potent inhibitor of HDAC class II Homo sapiens. The screening process result gave one best ligand, Nova2 (513246-99-6), which was then further studied by molecular dynamics simulations.

Dengue virus (DENV) has spread throughout the world, especially in tropical climates. Effective treatment of DENV infection is not yet available although several candidate vaccines have been developed. Treatment at this time is only to reduce symptoms and reduce the risk of death. Therefore, antiviral treatment is much needed. Envelope protein is one of the structural proteins of DENV which is known and could be a target of antiviral inhibitors and plays a special role in the fusion process. The aim of this research is to screen the commercial cyclic peptides which are used as inhibitors of envelope protein DENV through molecular docking and molecular dynamics at 310 and 312 K. Screening of commercial cyclic peptides through molecular docking ligands obtained best 10 ligands then examined the interaction between hydrogen bonding and residue contacts of the cavity envelope protein and obtained best three ligands which could enter the cavity of envelope protein overall. The three ligands were predicted through the ADME-Tox and the best ligand obtained was BNP (7-32), porcine. The results of molecular dynamics simulations at 310 and 312 K revealed that ligand can maintain interaction with the cavity of the target.

Cervical cancer is second most common cancer in woman worldwide. Cervical cancer caused by human papillomavirus (HPV) oncogene. Inhibition of histone deacetylase (HDAC) activity has been known as a potential strategy for cancer therapy. SAHA is an HDAC inhibitor that has been used in cancer therapy but still has side effects. SAHA modification proposed to minimize side effects. Triazole attachment on the chain of SAHA has been known to enhance the inhibition ability of SAHA and less toxic. In this study, it will be carried out with molecular dynamic simulations of SAHA modifications consisting ligand 1a, 2a and, 2c to interact with six HDAC in hydrated conditions. To all six HDAC Class II, performed docking with SAHA and a modified inhibitor. The docking results were then carried out molecular dynamics simulations to determine the inhibitor affinities in hydrated conditions. The molecular dynamic simulations results show better affinities of ligand 2c with HDAC 4, 6, and 7 than SAHA itself, and good affinity was also shown by ligand 2a and 1c on HDAC 5 and 9. The results of this study can be a reference to obtain better inhibitors.

The metabolic and regulatory capabilities of an organism are implicit in its protein content. This is often hard to estimate, however, due to ascertainment biases inherent in the available genome annotations. Its complement of recognizable functional protein domains and their combinations convey essentially the same information and at the same time are much more readily accessible, although protein domain models trained for one phylogenetic group frequently fail on distantly related sequences. Pooling related domain models based on their GO-annotation in combination with de novo gene prediction methods provides estimates that seem to be less affected by phylogenetic biases. We show here for 18 diverse representatives from all eukaryotic kingdoms that a pooled analysis of the tendencies for co-occurrence or avoidance of protein domains is indeed feasible. This type of analysis can reveal general large-scale patterns in the domain co-occurrence and helps to identify lineage-specific variations in the evolution of protein domains. Somewhat surprisingly, we do not find strong ubiquitous patterns governing the evolutionary behavior of specific functional classes. Instead, there are strong variations between the major groups of Eukaryotes, pointing at systematic differences in their evolutionary constraints.

Background: The cervical cancer is the second most prevalent cancer for the woman in the world. It is caused by the oncogenic human papilloma virus (HPV). The inhibition activity of histone deacetylase (HDAC) is a potential strategy for cancer therapy. Suberoylanilide hydroxamic acid (SAHA) is widely known as a low toxicity HDAC inhibitor. This research presents in silico SAHA modification by utilizing triazole, in order to obtain a better inhibitor. We conducted docking of the SAHA inhibitor and 12 modified versions to six class II HDAC enzymes, and then proceeded with drug scanning of each one of them., Results: The docking results show that the 12 modified inhibitors have much better binding affinity and inhibition potential than SAHA. Based on drug scan analysis, six of the modified inhibitors have robust pharmacological attributes, as revealed by drug likeness, drug score, oral bioavailability, and toxicity levels., Conclusions: The binding affinity, free energy and drug scan screening of the best inhibitors have shown that 1c and 2c modified inhibitors are the best ones to inhibit class II HDAC.