Chemical Biology Letters <p>Chemical Biology Letters is a peer reviewed journal for publication of research and review articles from Medicinal Chemistry, BioChemistry, Chemical Biology, Drug Development and Drug Delivery related studies.</p> ScienceIn Publishing en-US Chemical Biology Letters 2347-9825 Impact of Ayurvedic drug Tinospora cordifolia in hyperlipidemia induced dysbiosis <p>Gut microbiota broadly impacts human health, but urinary microbial metabolites remain largely undefined. The concentration of microbial metabolites can be directly correlated with microbial populations in the human gut to define disease states. <em>Tinospora cordifolia</em> (Willd.) Miers ex Hook. F. &amp; Thoms is being used for ages in the Indian ayurvedic system of medicine and it has hypolipidemic and hypoglycaemic activity. Present study investigate the MS-based metabolomics variations of possible gut microbiota associated metabolites in hyperlipidemia (HPL) and HPL treated with <em>Tinospora cordifolia</em> extract (TCE) (TRT). Twenty-four HPL male patients and 10 age-matched controls (HLT) were enrolled. Early morning fasting blood and urine samples were collected on days 0 and 14<sup>th</sup> of TCE treatment and subjected to lipid profiling and Q-TOF-MS analysis. Multivariate analysis showed urinary levels of urocanic acid, hydroxyphenylacetate, linolenic acid, phenylpropionate, hypoxanthine, and indole acetate produced by <em>Peptostreptococcs asaccharolyticus</em>, <em>Clostridium difficile</em>, <em>Faecalibacterium prausnitzii</em>, <em>Bifidobacterium</em>, <em>Subdoligranulum</em>, <em>Lactobacillus</em>, <em>Clostridium sporogenes</em>, <em>E</em>. <em>coli</em> were depleted in HPL patients as compared to healthy controls. In contrast, levels of serotonin, acetylleucine, hippuric acid, and arabinitol were found to be increased (&gt;2.0 fold, p&lt;0.005). However, TCE treatment reverted the levels of these metabolites and therefore, gut microflora. Also, <em>Cloacibacterium haliotis</em>, <em>Lactobacillus</em>, <em>Clostridium,</em> and <em>Bifidobacterium</em> population decreased in HPL patients. Increased secretion of yeast or <em>Candida albicans</em> associated metabolites was because of their increased population. Hence, TCE treatment enhanced the growth of useful gut microbiota in hyperlipidemia patients.</p> Aarti Yadav Amey Shirolkar Rajesh Dabur Copyright (c) 2022 ScienceIn Publishing 2022-04-24 2022-04-24 9 3 363 363 Establishment of in silico prediction methods for potential bitter molecules using the human T2R14 homology-model structure <p>Bitterness is sensed by human taste receptors (hT2Rs) consisting of G protein-coupled receptors (GPCRs). The construction of an <em>in silico</em> evaluation system for bitter molecules using human T2R structure information will enable the identification of new bitter molecules and bitter blockers, which will contribute to food and drug development. Since the crystal structures of the hT2Rs have not been elucidated, we attempted to construct <em>in silico</em> discrimination methods for potential bitter molecules using the hT2R14 model structure in the GPCRdb that was constructed by the homology modelling method. Although the hT2R14 model structure was constructed using characteristics of existing bitter molecules, it was not previously clear whether it could be used for the prediction of new bitter molecules and bitter blockers. In this study, we established novel methods of predicting potential bitter molecule interactions with hT2R14 using datasets of compounds from ChemBridge and FEMA GRAS libraries. We used docking simulation tools, molecular dynamics simulation tools, structure-based machine learning (ML) tools, and sequence-based ML tools to establish potential bitter molecule prediction systems for hT2R14. Finally, we constructed novel <em>in silico</em> prediction systems, one of which can evaluate potential bitter molecules with high accuracy (AUC = 0.850) using consensus scoring based on the structure-based ML tools OnionNet, GNINA and BAPA.</p> Kohei Kuriki Ryo Matsumoto Chiori Ijichi Junichi Taira Shunsuke Aoki Copyright (c) 2022 ScienceIn Publishing 2022-05-16 2022-05-16 9 3 351 351 Genome-wide mutation/SNP analysis, biological characteristics, and Pan-India prevalence of SARS-CoV-2 Variants of Concern <p>The origin of COVID-19 pandemic, caused by SARS-CoV-2, was traced to Wuhan, China. Thereafter, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolved into various variants owing to genome-wide mutations, causing emergence of multiple variants, including Variant of Interest and Variant of Concern. Here, we discuss genomic architecture of SARS-CoV-2, as well as its multiple variants- alpha, beta, gamma<strong>,</strong> and delta, along with their biological properties, such as transmissibility, reduction in antibody-mediated neutralization, virulence, disease severity, vaccine effectiveness, and the prevalence across the India <em>vis-à-vis</em> world. Our data on VOC, pooled from the Global Initiative on Sharing All Influenza Data up to 31 October 2021, shows around 89% prevalence of delta VOC across various Indian States. Whereas alpha, beta, and gamma variants show 10.44%, 0.57%, and 0.11% prevalence, respectively. Compared with global scale, the reported Indian prevalence of alpha, beta, gamma, and delta are 0.40%, 0.63%, 0.04%, and 1.7%, respectively. Furthermore, prevalent vaccines of various natures show significantly reduced effectiveness against these VOCs, necessitating urgent need for development of effective prophylactic vaccines and potential therapy to contain the pandemic.</p> Nimita Kant Shamashree Samanta Ishika Panchal Abhishek Pandey Lagna Ghatak Adyasha Rout Jitendra Kumar Chaudhary Copyright (c) 2022 ScienceIn Publishing 2022-02-16 2022-02-16 9 3 331 331 Use of Tyrosine Kinase Inhibitors for treating Type 2 Diabetes Mellitus: An appraisal <p>Tyrosine Kinase enzymes are known to play a significant role in tumor cell proliferation, stimulation of angiogenesis and metastasis and also show antiapoptotic effects. Therefore, Tyrosine Kinase inhibitors (TKIs) have been traditionally used to cure cancer. However, recently, there has been lot of interest in the possible use of TKIs for developing a new line of therapy for Type 2 Diabetes Mellitus (T2DM). Here, the authors have tried to summarize the seminal studies establishing the possible use of TKIs for T2DM. Authors conclude that there is lot of evidence suggesting the potential application of TKIs for treating T2DM, however, this hypothesis is still in its infancy stage. The animal models show promising results but there is an urgent need for detailed clinical investigations to establish this connection.</p> Kunika Saini Smriti Sharma Copyright (c) 2022 ScienceIn Publishing 2022-03-22 2022-03-22 9 3 320 320 Synthetic strategies and medicinal applications of Quinoline-Pyrimidine hybrids <p>The growing need to overcome the drug-resistance to bio-active molecules and the need for enhancement of properties in functional materials prompted the demand for new derivatives of existing moieties and development of more active new molecules. This effort culminated in the synthesis of a variety of molecules which often combined two active moieties into one single molecule such as the quinoline-pyrimidine hybrids. Quinoline-pyrimidine hybrids, though, include a wide class of molecules which vary based on the type of linkage combining the two moieties- quinoline and pyrimidine. This review focuses on these different classes of molecules, various developments in the synthesis of these hybrids and the biomedical applications of the synthesized molecules. Recently, greener methods like one-pot reactions and microwave assisted reactions have been utilized to synthesize some of the quinoline-pyrimidine hybrids and quite a few of the synthesized molecules have shown better or at par activity as the existing reference molecules.</p> Alitta Anna Cheriyan Libi Thomas Anchal Singhal Copyright (c) 2022 ScienceIn Publishing 2022-03-14 2022-03-14 9 3 318 318 Novel Inhibitors of malarial aspartyl proteases, plasmepsin II and IV: In silico design and validation studies <div> <p class="05Abstracttext"><span lang="EN-US">In the dire need of novel inhibitors of enzymes, computational approaches have significantly expedited the drug discovery process. Aspartic protease enzymes of Plasmodium falciparum such as plasmepsin II (<em>Pf</em></span><span lang="EN-US">Plm II) and plasmepsin IV (</span><em><span lang="EN-US">Pf</span></em><span lang="EN-US">Plm IV) have been recognized as an attractive drug target for antimalarial drug discovery. In line with this, we performed high-throughput screening of 316 novel compounds based on validated pharmacophore i.e., hydroxyethylamine (HEA) and piperazine against both PfPlm II and PfPlm IV. The obtained hit compound-protein complexes were subjected for molecular dynamics (MD) simulations at 200ns and found stable. Thermodynamic energy calculated for the complexes also supported compound’s stability within the binding pocket of plasmepsins. The results of our study strongly support an immediate validation of the virtually screened hits in biological systems.</span></p> </div> Prem Prakash Sharma Aaftaab Sethi Binit Dwivedi Maria Grishina Brijesh Rathi Geeta Singh Copyright (c) 2022 ScienceIn Publishing 2022-01-02 2022-01-02 9 3 315 315 Higher plants exert interspecific effects on the phytoecdysteroids contents in Tinospora cordifolia <p>Phytoecdysteroids are known for anabolic and adaptogenic properties. Hence, these are the point of interest in sports medicine and the pharmaceutical industry. Phytoecdysteroid occurrence varies in different plant parts, and also due to seasons and geographical locations. However, variations due to interspecific interactions of plants have not been explored to date. <em>Tinospora</em><em> cordifolia </em>has been reported to contain some phytoecdysteroids and is known to have anabolic and rejuvenating properties. Hence, the effect of interspecific interactions on phytoecdysteroid contents was explored in the current study using HPLC-QTOF-MS. Initial analysis of mass data based on characteristic fragment ions and loss of multiple water molecules validated the presence of 10 phytoecdysteroids and 4 derivatives across the samples screened. Principle component analysis (PCA) and partial least square discriminant analysis (PLS-DA) analysis showed significant (p&gt;0,05) variations in phytoecdysteroid patterns due to interspecific interactions. Statistical analysis revealed that&nbsp;<em>T. cordifolia </em>having interactions with &nbsp;<em>A</em>. <em>lebbeck</em>&nbsp;and&nbsp;<em>A</em>.&nbsp;<em>nilotica</em> formed separate distant groups, whereas. <em>T. cordifolia </em>having interactions with<em> A</em>.&nbsp;<em>indica</em>&nbsp;is the most distant group among other groups. <em>T. cordifolia</em> co-occurred with&nbsp;<em>A</em>.&nbsp;<em>indica</em>&nbsp;showed the highest number of up-regulated phytoecdysteroids, Fold change analysis showed that interspecific interactions of <em>T. cordifolia</em> with <em>A. indica</em> increased the contents of 3-dehydroecdysone (2-fold), makisterone A (4.8-fold), 24-methylshidasterone (4.3-fold), 1-hydroxy-20,22-didehydroxysterone (2-fold), 1-hydroxy-22-deoxy-20,21-dehydroecdysone (2-fold), cycleasterone A(3.3-fold), and 3β,5α,14α-trihydroxyergosta-7,22-diene-6-one (2.5-fold) in comparison to other plants. Hence, study indicate the interspecific interactions with&nbsp;<em>T. cordifolia</em>&nbsp;change the phytoecdysteroids pattern, hence its medicinal properties.</p> Aarti Yadav Surender Yadav Rajesh Dabur Copyright (c) 2022 ScienceIn Publishing 2022-02-01 2022-02-01 9 3 312 312 Source optimization, characterization, assessing biocompatibility and drug loading efficiency of biogenic silica particles from agro wastes <p>Biogenic Silica Nanoparticles (BSN) were manufactured from different agro-wastes and their physico-chemical characterization and suitability as a drug carrier were tested. All the starting materials yielded high purity BSN, but the percentage of yield differed, with Indian goose grass and rice husk giving the highest percentage yield. Different conditions adopted in the manufacture were found to affect the amorphous nature of BSN produced. The BSN remained amorphous and porous at temperatures below 700°C. BSN at 500°C was found to have the best surface area and zeta potential which was found favorable in drug surface modifications and drug loading. BSN was not toxic to cells up to 200µg/mL and slightly improved the antioxidant response. Rice husk is a viable by-product of rice milling industry which can be used as a precursor for biogenic silica. Acid treatment followed by calcination at 500°C yielded high-quality BSN. Different physical characterization using SEM, TEM, BET, XRD, XRF etc revealed that the particles are spherical with 50-100 nm diameters and surface area 232m<sup>2</sup>/g. The prepared BSN were highly pure (&gt;99%). The cell viability study revealed the excellent biocompatibility of BSN. Propidium Iodide staining had shown that there were no significant changes in the nuclear morphology of the cells treated with BSN. Curcumin loaded BSN showed a slightly better ameliorating effect on the oxidative stress response caused by cypermethrin treatment than free curcumin alone. Surface modification of BSN with PEG and chitin was found to improve the antioxidant power of BSN and its drug loading efficiency. All these in vitro observations suggest the possibility of harnessing BSN isolated from rice husk as an effective drug carrier, or for other biomedical applications.</p> Aparna A Menon Radhakrishna Gopala Pillai Copyright (c) 2022 ScienceIn Publishing 2022-01-09 2022-01-09 9 3 311 311 In silico study of phytochemicals for anticholinesterase activity as a potential drug target against Alzheimer's disease <p>Alzheimer's disease (AD) is characterized by down-regulated levels of neurotransmitter acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) in the neocortex and hippocampus; and aberrant processing and polymerization of Amyloid Precursor Protein (APP). Inhibition of cholinesterase (ChE) activity will effectively measure in AD treatment. In the present study, in silico analysis of anticholinesterase activity by 18 plant phytochemicals revealed four phytochemicals Quercetin, Cirsimaritin, Genkwanin and Genistein could be potential drugs candidates as they showed high binding affinity and interaction with the target protein AchE and BchE. These phytochemicals may play an essential role in regulating ChE activity in AD patients. Also, they are previously reported to play a vital role in altering other AD contributing factors. Thus, the present study reports potential drug targets that can be used to develop a drug against AD after experimental validation.</p> Tushar T Khandagale Kuldeepkumar Singh Sangeeta Sinha Akshita Puri Copyright (c) 2022 ScienceIn Publishing 2022-02-22 2022-02-22 9 3 310 310 A comprehensive review on therapeutic properties of Mustard Oil and Olive Oil <p>Plants and their extracts have been extensively studied for their efficacy in therapeutic applications. Their Essential Oils (EOs) are responsible for the majority of biological properties such as anticancer, antibacterial and antimicrobial, antioxidant, anti-inflammatory, and cardio-protective. The utilization of natural compounds is gaining a lot of attention these days. These oils act as natural alternatives to the modern medical system to cure the illness that occurs in the biological system. This review provides an overview of the impact of the two most important plant-based oils: Mustard oil and Olive oil, the role of their components in different biological activities leading to their therapeutic applications. Their intake provides health benefits by controlling the symptoms of the diseases that involve cancer, bacterial infections, inflammation, cardiovascular, and some other common diseases. Most of the results come from <em>in vitro</em> and <em>in vivo</em> studies. However, their use in clinical studies is very little known.</p> Tarisha Gupta Ratandeep Pooja Laishram Saya Copyright (c) 2021 ScienceIn Publishing 2021-12-08 2021-12-08 9 3 309 309 Paraquat treatment modulated the stress erythropoiesis response in bone marrow and liver of the splenectomized mice <p>Spleen serves as a secondary lymphoid and primary erythropoietic organ in neonates and in acute anemic conditions. Splenectomy is the process of surgical removal of spleen, which is used for the treatment of a number of anemic, leukemia and lymphoma patients. In the present investigation, we have analyzed the modulation of stress erythropoietic response in splenectomized condition. The splenectomized mice were treated with the repeated doses of paraquat (10 mg/kg intra-peritoneal on alternate days). Erythroid progenitor cells in bone marrow and liver were examined by staining with the anti-glycophorin (anti-Ter119) and transferrin (CD71) and monitoring the receptor expression. Paraquat treatment shows a moderate effect on the blood erythrocytes count, hemoglobin levels and reticulocytes percentages in blood circulation however induced the production of reactive oxygen species (ROS) in erythrocytes of splenectomized mice. The relative proportions and absolute recoveries of erythroid precursor cells in bone marrow were declined significantly at earlier time points post paraquat treatments. However, these cells begin to recover from day 14 and 21 and come to basal level on day 28. The proportion of erythroid cells in liver was slightly decreased on day 7 but it increased significantly on day 14. Interestingly, the proliferative activity of erythroid cells in the bone marrow increases, probably to compensate the loss of erythrocytes in circulation</p> Nitin Bhardwaj Ashutosh Singh Harish Chandra Kartikey Kumar Gupta Copyright (c) 2022 ScienceIn Publishing 2022-02-26 2022-02-26 9 3 306 306 Reverse vaccinology based in silico analysis of Epitope prediction in cya, lef and pagA genes from Bacillus anthracis against Anthrax infected species: An Immunoinformatics approach <p>Bacillus anthracis is a Gram-positive spore-forming bacterium that causes the zoonotic disease: anthrax, an abrupt illness that disproportionately impacts grazing livestock and wild ruminants. The anthrax’s geographical reach despite years of research on anthrax epizootic and epidemics behaviour, till date remains to be elucidated. Existing therapeutics, however, are ineffective in combating this infectious disease, necessitating the development of a better vaccine to pause the pandemic using immunoinformatics approaches, this study intended to predict an efficient epitope for vaccine against the anthrax in animals and humans of the toxin genes such as cya, lef and pagA of B.anthracis against anthrax. The B-cell and T-cell epitopes were predicted utilizing various bioinformatics tools/software and docking analysis was performed. Consequently, it was found that the evaluated epitopes had no allergenicity, no toxicity and had high antigenicity that provides an effectual and most rapid technique to estimate peptide synthetic vaccines to impede the anthrax.</p> Uma Bharathi Indrabalan Suresh Kuralayanapalya Puttahonnappa Mallikarjun S Beelagi Sharanagouda S Patil Chandan Shivamallu Mohan Pappana Raghavendra Amachawadi Copyright (c) 2022 ScienceIn Publishing 2022-02-27 2022-02-27 9 3 295 295 Panax ginseng as reproductive medicine in male infertility: with a brief focus on herb-drug interaction <p>Male infertility is referred to as the lack of ability of the male to impregnate his fertile female partner even after 12 months of unprotected, frequent sexual contact. It affects anywhere from 9 percent to 15.8percent of the general population. Male infertility can be treated with a variety of conventional methods, but the effectiveness of this therapy is still under research. Complementary and alternative medicine is frequently sought by those suffering from infertility issues. In many cases, herbal medicine, for example maca, dang gui, or ginseng are applied try to ameliorate male fertility, libido, and sexual functions. Ginseng, as a cyclic adenosine monophosphate-responsive element modulator, has been shown in several preclinical investigations to stimulate spermatogenesis, as well as to improve testicular functions, sperm quality, and motility.</p> Pallav Sengupta Sulagna Dutta Copyright (c) 2022 ScienceIn Publishing 2022-01-04 2022-01-04 9 3 279 279 Clinical status of potential drugs used for COVID-19 treatment and recent advances in new therapeutics - A review <p>COVID-19, a perilous disease caused by SARS-CoV-2, has brought a massive damage to humankind, and turned into a global catastrophe. It was first reported in Wuhan, China in December 2019 and since then has been a constant source of worry for the scientists and the medical world, due to the carnage it has caused globally. Extensive clinical studies are being carried to explore drug therapy and prophylaxis to combat this pestilence.&nbsp; It is still an excessively big challenge for the scientists and pharmacological industry to develop potential drugs for the treatment of this deadly virus. At present though no specific drug has been identified as a perfect cure for this zoonotic disease, medical practitioners are using the therapy of repurposing of drugs for the treatment. Systemic research was carried out through e-resources to identify drugs for the treatment of COVID-19. A recent proposal of 2-DG drug as a cure for COVID-19 has also been discussed in this review.</p> Kalpa Mandal Meenakshi Singh Charu Chandra Indraj Kumar Kumawat Copyright (c) 2021 ScienceIn Publishing 2021-09-21 2021-09-21 9 3 117 128 A comparative study of isothermal nucleic acid amplification methods for SARS-CoV-2 detection at point-of-care <p>COVID-19, caused by the novel coronavirus SARS-CoV-2, has put most of the world under lockdown. Despite approved vaccines, COVID-19 cases, hospitalizations, and deaths have remained on the rise. Rapid diagnosis and necessary public health measures are still key parts to contain the pandemic. Here, the colorimetric isothermal nucleic acid amplification tests (iNAATs) for SARS-CoV-2 detection based on loop-mediated isothermal amplification (LAMP), cross-priming amplification (CPA), and polymerase spiral reaction (PSR) were designed and compared in performance for the first time. The findings showed that, for the detection of SARS-CoV-2 genomic-RNA, LAMP outperformed both CPA and PSR, exhibiting the limit of detection (LOD) of roughly 43.14 copies/reaction. The results can be read with the naked eye within 45 minutes, without cross-reactivity to closely related coronaviruses. The direct detection of SARS-CoV-2 RNA in simulated specimens by iNAATs was also successful. Additionally, the lyophilized reagents for LAMP reactions maintained the sensitivity and LOD of the liquid assays. The colorimetric LAMP assay was validated using clinical samples, showing 98.1% sensitivity and 100% specificity upon using extracted samples and 82.4% sensitivity and 86.2% specificity upon using unextracted specimens. The results indicate that the direct colorimetric LAMP assay developed is highly suitable for detecting SARS-CoV-2 at point-of-care.</p> Diem Hong Tran Hoang Quoc Cuong Hau Thi Tran Uyen Phuong Le Hoang Dang Khoa Do Le Minh Bui Nguyen Duc Hai Hoang Thuy Linh Nguyen Thi Thanh Thao Nguyen Hoang Anh Nguyen Trung Hieu Cao Minh Thang Van Van Vu Huong Thi Thu Phung Copyright (c) 2021 ScienceIn Publishing 2021-09-25 2021-09-25 9 3 106 116