Aspects of molecular medicine最新文献

{"title":"Linkage and association of rs3110045 and rs28499085 variants in the thyrotropin-releasing hormone receptor (TRHR) gene with the risk of familial type 2 diabetes","authors":"Rongling Wu ,&nbsp;Claudia Gragnoli","doi":"10.1016/j.amolm.2024.100037","DOIUrl":"https://doi.org/10.1016/j.amolm.2024.100037","url":null,"abstract":"<div><p>Type 2 diabetes (T2D) is a chronic and prevalent multisystemic disease that significantly increases morbidity and mortality. Dysfunction of the thyroid hormone system is common in patients with T2D, increasing their risk of both hyperthyroidism and hypothyroidism. Several components of the thyroid system are candidate risk genes for T2D. The thyrotropin-releasing hormone receptor (<em>TRHR</em>) gene encoding for TRHR is of particular interest since it is expressed by the dorsomedial hypothalamus neurons, which are known to regulate food intake. In humans, a variant in the <em>TRHR</em> gene has been previously reported in T2D patients in a population-based case-control study but not in familial T2D. We recruited 212 multigenerational families with T2D originated from the Italian peninsula with multiple cases of T2D and tested, via Pseudomarker 9 single nucleotide polymorphisms (SNPs) in the <em>TRHR</em> gene for linkage and linkage disequilibrium (i.e., linkage plus association) to/with T2D. We identified 2 novel risk variants (rs3110045 and rs28499085) significantly linked to and associated with the risk of T2D in the Italian families across several inheritance models. Our study is the first to confirm the previously reported association of <em>TRHR</em> gene with T2D and extends the risk to familial inheritance. However, functional and replication studies are still needed to confirm these results.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"3 ","pages":"Article 100037"},"PeriodicalIF":0.0,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688824000042/pdfft?md5=991c4d762c3e7d22a03c38d84b2e59ed&pid=1-s2.0-S2949688824000042-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139999854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the potential of natural compounds and known drugs against obstructive airway inflammation in inhibiting TRPC6","authors":"Uzma Saqib ,&nbsp;Isaac S. Demaree ,&nbsp;Alexander G. Obukhov ,&nbsp;Krishnan Hajela","doi":"10.1016/j.amolm.2024.100036","DOIUrl":"https://doi.org/10.1016/j.amolm.2024.100036","url":null,"abstract":"<div><p>The Transient Receptor Potential Canonical 6 (TRPC6) channel was implicated in the pathogenesis of pulmonary airway inflammation, chronic obstructive pulmonary disease, pulmonary edema, and pulmonary fibrosis. It was also proposed that Ca²⁺ influx through TRPC6 may contribute to triggering pulmonary inflammatory responses. The ChEMBL database lists 44 drugs that are clinically used to treat asthma, a type of obstructive airway inflammation (OAI). Since the mode of action and targets are not fully elucidated for many of these 44 drugs, we used computational approaches to determine the drugs’ potential to interact with the inhibitor binding site on the TRPC6 protein. We also screened a library of natural compounds to retrieve the phytochemicals with a potential to interact with TRPC6. The binding affinities of two well-known TRPC6 inhibitors, BTDM and 2-aminoethoxydiphenyl borate (2-APB), were compared with those of the screened compounds. We found that despite stable <em>in silico</em> binding and a well-defined three-dimensional molecular interaction pattern with the TRPC6 protein of the two top-scoring compounds, montelukast and solanesol, the molecules from the approved-drug and natural-compound libraries respectively, failed to show any significant efficacy in the <em>in vitro</em> assays.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"3 ","pages":"Article 100036"},"PeriodicalIF":0.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688824000030/pdfft?md5=b75db9a2af1a0785cfdb9500fcef112b&pid=1-s2.0-S2949688824000030-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139749606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-hepatopathy and anti-nephropathy activities of Taraxacum officinale in a rat model of Streptozotocin diabetes-induced hepatorenal toxicity and dyslipidemia via attenuation of oxidative stress, inflammation, apoptosis, electrolyte imbalances, and mitochondrial dysfunction","authors":"Sunday Aderemi Adelakun ,&nbsp;Aniah Julius Akomaye ,&nbsp;Olusegun Dare Omotoso ,&nbsp;Olukayode Abimbola Arowosegbe","doi":"10.1016/j.amolm.2024.100034","DOIUrl":"10.1016/j.amolm.2024.100034","url":null,"abstract":"<div><p>Diabetes and chronic liver and kidney disease are common long-term conditions worldwide. <em>Taraxacum officinale</em> (TOE) has many medicinal properties, due to it phytochemicals constitutions. This study investigate activities of TOE in Streptozotocin diabetes-Induced Hepatorenal toxicity. Sixty rats were randomized into groups A, B, C, D, E, and F of ten rats each (n = 10). Group normal control, group B treated with TOE, group C diabetic (DM) negative control, group D DM rats treated with TOE, group E DM rats treated with metformin (MF)], group F treated with TOE follow by STZ-diabetic). Serum lipid profile, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), Gamma-glutamyl transferase (GGT), total proteins (TP), albumin (ALB), Urea, and creatinine, electrolyte, oxidative and antioxidant enzymes, caspase 3, inflammatory cytokines, tricarboxylic acid (TCA) cycle enzymes and mitochondrial membrane potential (ΔΨm), liver and kidney histology were investigated.</p><p>Treatment with TOE ameliorated all the electrolyte disruptions in DM rats. Treatment with TOE and TOE + MF recovered caspase 3, inflammatory makers, oxidative and antioxidant enzymes in DM rats. Moreover, an increase in lipid profile, hepatic and renal functional markers, ALT, AST, ALP, GGT, TP, ALB, Urea, TCA and renal mitochondrial respiratory-chain complexes (I-IV) and ΔΨm and a decrease in creatinine clearance was recovered in DM rats by TOE and TOE + MF treatment. TOE and TOE + MF protected against hepatic and renal histological damage in DM group.</p><p>Hepatorenal toxicity was effectively ameliorated by the TOE administration. TOE might be considered as a potential protective agent against hepatorenal toxicity.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"3 ","pages":"Article 100034"},"PeriodicalIF":0.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688824000017/pdfft?md5=fc7fa944b7cdfb215ed7cdfcbb1619a4&pid=1-s2.0-S2949688824000017-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139831807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human serum albumin binds spike protein and protects cells from SARS-CoV-2 infection by modulating the RAS pathway","authors":"Romualdo Varricchio ,&nbsp;Giovanna De Simone ,&nbsp;Gian Marco Vita ,&nbsp;Walter Nocera Cariola ,&nbsp;Maurizio Viscardi ,&nbsp;Sergio Brandi ,&nbsp;Gerardo Picazio ,&nbsp;Verena Zerbato ,&nbsp;Raffaella Koncan ,&nbsp;Ludovica Segat ,&nbsp;Stefano Di Bella ,&nbsp;Giovanna Fusco ,&nbsp;Paolo Ascenzi ,&nbsp;Alessandra di Masi","doi":"10.1016/j.amolm.2023.100033","DOIUrl":"10.1016/j.amolm.2023.100033","url":null,"abstract":"<div><p>Since the start of the pandemic, scientists have directed their research towards identifying COVID-19 risk factors and predictive elements. Numerous clinical studies have established a strong connection between hypoalbuminemia and an unfavorable prognosis for COVID-19. Here, we aim to explore the impact of human serum albumin (HSA) on SARS-CoV-2 infection. Our findings indicate that HSA plays a role in reducing the replication rate of SARS-CoV-2 in Vero E6 cells. This protective effect is due to HSA ability to bind to the S1 domain of the spike protein, effectively competing with ACE2. Moreover, we show that the protective role of HSA is dependent also on its ability to activate the protective axis within the RAS system pathway, which is responsible for inducing vasodilation and promoting anti-inflammatory, anti-fibrotic, and anti-apoptotic responses. In summary, the data presented in this study support the idea that reduced levels of circulating HSA in hypoalbuminemic patients may heighten their susceptibility to SARS-CoV-2 infection, as the spike protein is unhindered in its ability to bind to ACE2 and penetrate human cells. Besides, hypoalbuminemia exacerbates the imbalance of the RAS pathway towards the classical “detrimental” axis. This could potentially contribute to the increased severity and elevated mortality rate observed in individuals with low levels of circulating albumin.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"3 ","pages":"Article 100033"},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688823000333/pdfft?md5=0c53d54701d04e1e52bec07beb4f8e52&pid=1-s2.0-S2949688823000333-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139013329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico study of the flavonoid compound of Sauropus androgynus leaves ON RNA-Dependent RNA polymerase (RdRp) SARS-CoV-2","authors":"Aghnia Nabila Ananda ,&nbsp;Triawanti Triawanti ,&nbsp;Bambang Setiawan ,&nbsp;Annisa Camellia Makati ,&nbsp;Jasmine Aisyah Putri ,&nbsp;Sentot Joko Raharjo","doi":"10.1016/j.amolm.2023.100032","DOIUrl":"10.1016/j.amolm.2023.100032","url":null,"abstract":"<div><h3>Objective</h3><p>RNA-dependent RNA polymerase (RdRp) is a protein that is essential in the replication and transcription processes of SARS-CoV-2. RdRp inhibitors must be sought, particularly in the identification of active substances in herbal or human dietary sources. The purpose of this study was to investigate the molecular docking of phytochemistry from the leaves of <em>Sauropus androgynus</em> against the RdRp protein.</p></div><div><h3>Methods</h3><p>This in silico study was performed using AutoDock Tools 1.5.7, AutoDock Vina v1.2.3 software, and BIOVIA Discovery Studio Visualizer 4.1.</p></div><div><h3>Results</h3><p>Afzelin, kaempferol, and trifolin were found as phytochemistry in Sauropus androgynus leaves. Among the three flavonoid molecules, afzelin has the lowest negative binding affinity (−7.677 kcal/mol), followed by trifolin (−6.906 kcal/mol) and kaempferol (−6.65 kcal/mol). All three flavonoid compounds have a binding affinity that is more negative than the three conventional drugs (favipiravir, remdesivir, ribavirin).</p></div><div><h3>Conclusions</h3><p>Flavonoid from the leaves of <em>Sauropus androgynus</em> leaves can be utilized as candidate for herbal or complementary medicine as an inhbitor of RdRp for COVID-19 treatment.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"3 ","pages":"Article 100032"},"PeriodicalIF":0.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688823000321/pdfft?md5=0d7af3c65653d94265a12879357adc18&pid=1-s2.0-S2949688823000321-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138615677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mefenamic acid inhibit transforming growth factor-beta type-1: Repurposing anti-inflammatory drugs in wound healing using in-silico approaches","authors":"Miah Roney ,&nbsp;Abdul Rashid Issahaku ,&nbsp;Normaiza Binti Zamri ,&nbsp;Mohd Fadhlizil Fasihi Mohd Aluwi","doi":"10.1016/j.amolm.2023.100031","DOIUrl":"https://doi.org/10.1016/j.amolm.2023.100031","url":null,"abstract":"<div><p>Due to low cost and time-saving benefits, drug repurposing is a safe and successful method to discover drug. A druggable target for inflammation, transforming growth factor-beta type-1 (TGF-β 1) has been identified to be associated with wound healing. Finding the most effective TGF-β 1 inhibitor among FDA-approved anti-inflammatory medications was the goal of the current investigation. To find the best hits against TGF-β 1, we used structure-based virtual screening on medications that have received FDA approval. We discovered two FDA-approved medications with notable selectivity and affinity for the binding pocket of TGF-β 1. Mefenamic acid, one of these found hits, interacts with key TGF-β 1 residues and favourably attaches to the binding pocket, requiring further study. The kinetics of the binding between mefenamic acid and TGF-β 1 were revealed by all-atom precise molecular dynamics (MD) simulations. Mefenamic acid, which may also be used as a possible lead chemical against TGF-β 1, may be a promising TGF-β 1 inhibitor.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"2 ","pages":"Article 100031"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S294968882300031X/pdfft?md5=f66163663185f30d3e426aa14a2f9faf&pid=1-s2.0-S294968882300031X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138467100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationship between genetic ancestry and metabolic syndrome in community-dwelling old adults","authors":"Jamille Silva Oliveira ,&nbsp;Gabriel Novaes Miranda ,&nbsp;Icaro J.S. Ribeiro ,&nbsp;Ivna Vidal Freire ,&nbsp;Cezar Augusto Casotti ,&nbsp;Ana Angélica Leal Barbosa ,&nbsp;Rafael Pereira","doi":"10.1016/j.amolm.2023.100027","DOIUrl":"10.1016/j.amolm.2023.100027","url":null,"abstract":"<div><p>Genetic ancestry may contribute to ethnic differences in the risk of metabolic disorders. Aging leads to a worse ability for homeostasis maintenance, favoring the establishment of metabolic disorders.</p></div><div><h3>Purpose</h3><p>This study aimed to evaluate the relationship between the degree of genetic ancestry (European, African, and Amerindian) with the Metabolic Syndrome (MetS) diagnosis and its diagnostic components separately, in community-dwelling old adults. One hundred and sixty-one community-dwelling old adults volunteered in this study. Sociodemographic data and health history were recorded. Venous blood samples were withdrawal for biochemical analysis and DNA extraction aiming to obtain genetic ancestry estimates (Amerindian [AME], European [EUR], and African [AFR]), which was done from 12 loci. MetS diagnosis followed the NCEP-ATPIII criteria. Additionally, the sample was stratified according to the presence or absence of each criterion used for MetS diagnosis (i.e., Type 2 diabetes mellitus (T2DM), hypertension, hypertriglyceridemia, dyslipidemia [low HDL], and central obesity (elevated waist circumference)). Comparisons of genetic ancestry estimates were performed using the Mann-Whitney test, with the significance level set at p &lt; 0.05. The prevalence of MetS was 40.4%. The degree AME, EUR and AFR genetic ancestry was not different between volunteers with or without MetS (p &gt; 0.05). However, AME ancestry was significantly higher among diabetic volunteers (non-diabetics: 13.7% (6.3–35.8) x Diabetics: 26.1% (10.6–48.5); p &lt; 0.05). Community-dwelling old adults with a higher percentage of Amerindian ancestry seem to be prone to T2DM diagnosis.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"2 ","pages":"Article 100027"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688823000278/pdfft?md5=5622aed5070444ef6d4e6cf7cf3dd1a0&pid=1-s2.0-S2949688823000278-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135669985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Academic examination stress: Effects on salivary cortisol, neuropeptide Y and interleukin-1β","authors":"Rabia Şemsi ,&nbsp;Erdal Ergünol ,&nbsp;Emre Kanad Er ,&nbsp;Aylin Sepici Dinçel","doi":"10.1016/j.amolm.2023.100030","DOIUrl":"https://doi.org/10.1016/j.amolm.2023.100030","url":null,"abstract":"<div><p>Saliva is one of the preferred non-invasive body fluids for biomarker studies. This study aimed to investigate the possible alteration of stress biomarkers of the students before and after the examinations via salivary cortisol, neuropeptide Y (NPY), and Interleukin-1β (IL-1β) levels. Forty-four adults were included in the study and divided into groups of pre-examination (Group I) and post-examination (Group II). Salivary samples were collected between 8 and 9 a.m. before and after the exam, which ended at 5 p.m. by SARSTEDT saliva collection tubes. Participants were asked to soak the swab with saliva and take it out after 1 min. Swabs were kept at room temperature for 15–30 min and centrifuged for 10–15 min at 1500 g. Salivary cortisol (ng/mL), NPY (ng/mL), and IL-1β (pg/mL) levels were analyzed by Enzyme-linked immunosorbent assay (ELISA). The salivary cortisol, NPY and IL-1 β levels were significantly increased in Group II compared to Group I (9.65 ± 4.53, 6.37 ± 4.14, p &lt; 0.019; 32.12 ± 4.69, 27.10 ± 4.71 p &lt; 0.001; 11.69 ± 3.61, 7.20 ± 3.49, p &lt; 0.0003 respectively). The IL-1β levels were positively and significantly correlated with salivary cortisol and NPY levels in Group II (r = 0.642, p = 0.03; r = 0.589, p = 0.004, respectively). Also, IL-1β levels were positively and significantly correlated with salivary NPY levels in Group I (r = 0.430, p = 0.04). These data indicated that acute stress can alter the inflammatory response and increase NPY release, which is positively associated with cortisol.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"2 ","pages":"Article 100030"},"PeriodicalIF":0.0,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688823000308/pdfft?md5=9a681beb8339e4ab09c51cfa49dfdbe4&pid=1-s2.0-S2949688823000308-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138413594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiome associated dysbiosis: Limited regimens and expanding horizons of phage therapy","authors":"Biplab Singha ,&nbsp;Bhupendra Singh Rawat ,&nbsp;Ramya Venkataraman ,&nbsp;Tripti Nair ,&nbsp;Eric H. Rosenn ,&nbsp;Vijay Soni","doi":"10.1016/j.amolm.2023.100029","DOIUrl":"https://doi.org/10.1016/j.amolm.2023.100029","url":null,"abstract":"<div><p>Human gut microbiota plays an important role in health, broadly influencing metabolism to the immune system and drug resistance to pathogenic colonization. Since antibiotic resistance is on the rise, and wide-spectrum antibiotics are known to have deleterious effects on microbial biodiversity targeted therapeutic interventions must be made. Bacteriophages are viruses that are commonly recognized to have a high level of specificity, targeting only the intended bacterial species without disrupting the overall microbial community. Advancements in genomics, bioinformatics, and synthetic biology led us to the identification and design of phages, capable of precisely targeting specific pathogens. In this review article, we aim to discuss both the challenges and opportunities of integrating phage therapies into clinical practice, discussing the limitations of traditional therapy as it pertains to the manipulation of the gut microbiome.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"2 ","pages":"Article 100029"},"PeriodicalIF":0.0,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2949688823000291/pdfft?md5=1315a9379986533a4d8a50b610b53379&pid=1-s2.0-S2949688823000291-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138437682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitory effect of Sinapic acid derivatives targeting structural and non-structural proteins of dengue virus serotype 2: An in-silico assessment","authors":"Miah Roney ,&nbsp;Amit Dubey ,&nbsp;Normaiza Binti Zamri ,&nbsp;Mohd Fadhlizil Fasihi Mohd Aluwi","doi":"10.1016/j.amolm.2023.100028","DOIUrl":"https://doi.org/10.1016/j.amolm.2023.100028","url":null,"abstract":"<div><p>DENV infects 50–100 million individuals, and 500,000 of them go on to acquire the more serious dengue hemorrhagic fever, which causes around 20,000 fatalities every year. Despite its widespread nature, there is no medication licenced to treat this condition. The purpose of this work is to identify <em>anti</em>-DENV medicines from sinapic acid (SA) derivatives utilising in-silico evaluation through docking and pharmacokinetics investigations. For the DENV-2 envelop protein, 1-<em>O</em>-β-<span>d</span>-glucopyranosyl sinapate had a significant docking score of −7.7 kcal/mol, while sinapoyl malate had a docking score of −6.7 kcal/mol for the DENV-2 NS2B/NS3 protein. Additionally, according to the PASS server, 1-<em>O</em>-β-<span>d</span>-glucopyranosyl sinapate and sinapoyl malate have a wide range of enzymatic activities since their probability active (Pa) values is &gt; 0.700. These compounds exhibit a numerous pharmacological effect through activating the body's enzymes, according to analyses of their pharmacokinetic qualities. Accordingly, these substances showed acute toxicity rates at LD50 log10 (mmol/g) and LD50 (mg/g) concentrations when administered via various routes, including intraperitoneal, intravenous, oral, and subcutaneous. The result of this research suggests, 1-<em>O</em>-β-<span>d</span>-glucopyranosyl sinapate and sinapoyl malate may function as possible inhibitors to halt the DENV, and more in-vitro and in-vivo research is required to validate their activity and other features.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"2 ","pages":"Article 100028"},"PeriodicalIF":0.0,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S294968882300028X/pdfft?md5=3d3d845efe3147fd6769e3d568c51c04&pid=1-s2.0-S294968882300028X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134656524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}