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Hepatitis C virus (HCV) is a dangerous virus that is responsible for a large number of infections and deaths worldwide. In the treatment of HCV, it is important that the drugs are effective and do not have additional hepatotoxic effects. The aim of this study was to test the in silico activity of 1893 terpenes against the HCV NS5B polymerase (PDB-ID: 3FQK). Two drugs, sofosbuvir and dasabuvir, were used as controls. The GOLD software (CCDC) and InstaDock were used for docking. By using the results obtained from PLP.Fitness (GOLD), pKi, and binding free energy (InstaDock), nine terpenes were finally selected based on their scores. The drug-likeness properties were calculated using Lipinski’s rule of five. The ADMET values were studied using SwissADME and pkCSM servers. Ultimately, it was shown that nine terpenes have better docking results than sofosbuvir and dasabuvir. These were gniditrin, mulberrofuran G, cochlearine A, ingenol dibenzoate, mulberrofuran G, isogemichalcone C, pawhuskin B, 3-cinnamyl-4-oxoretinoic acid, DTXSID501019279, and mezerein. Each docked complex was submitted to 150 ns-long molecular dynamics simulations to ascertain the binding stability. The results show that mulberrofuran G, cochlearine A, and both stereoisomers of pawhuskin B form very stable interactions with the active site region where the reaction product should form and are, therefore, good candidates for use as effective competitive inhibitors. The other compounds identified in the docking screen either afford extremely weak (or even hardly any) binding (such as ingenol dibenzoate, gniditrin, and mezerein) or must first undergo preliminary movements in the active site before attaining their stable binding conformations, in a process which may take from 60 to 80 ns (for DTXSID501019279, 3-cinnamyl-4-oxoretinoic acid or isogemichalcone C).

Loss of tubulin is associated with neurodegeneration and brain aging. Turmeric (Curcuma longa L.) has frequently been employed as a spice in curry and traditional medications in the Indian subcontinent to attain longevity and better cognitive performance. We aimed to evaluate the unelucidated mechanism of how turmeric protects the brain to be an anti-aging agent. D. melanogaster was cultured on a regular diet and turmeric-supplemented diet. β-tubulin level and physiological traits including survivability, locomotor activity, fertility, tolerance to oxidative stress, and eye health were analyzed. Turmeric showed a hormetic effect, and 0.5% turmeric was the optimal dose in preventing aging. β-tubulin protein level was decreased in the brain of D. melanogaster upon aging, while a 0.5% turmeric-supplemented diet predominantly prevented this aging-induced loss of β-tubulin and degeneration of physiological traits as well as improved β-tubulin synthesis in the brain of D. melanogaster early to mid-age. The higher concentration (≥ 1%) of turmeric-supplemented diet decreased the β-tubulin level and degenerated many of the physiological traits of D. melanogaster. The turmeric concentration-dependent increase and decrease of β-tubulin level were consistent with the increment and decrement data obtained from the evaluated physiological traits. This correlation demonstrated that turmeric targets β-tubulin and has both beneficial and detrimental effects that depend on the concentration of turmeric. The findings of this study concluded that an optimal dosage of turmeric could maintain a healthy neuron and thus healthy aging, by preventing the loss and increasing the level of β-tubulin in the brain.

Angiotensin-converting enzyme 2 (ACE2), also known as peptidyl-dipeptidase A, belongs to the dipeptidyl carboxydipeptidases family has emerged as a potential antiviral drug target against SARS-CoV-2. Most of the ACE2 inhibitors discovered till now are chemical synthesis; suffer from many limitations related to stability and adverse side effects. However, natural, and selective ACE2 inhibitors that possess strong stability and low side effects can be replaced instead of those chemicals' inhibitors. To envisage structurally diverse natural entities as an ACE2 inhibitor with better efficacy, a 3D structure-based-pharmacophore model (SBPM) has been developed and validated by 20 known selective inhibitors with their correspondence 1166 decoy compounds. The validated SBPM has excellent goodness of hit score and good predictive ability, which has been appointed as a query model for further screening of 11,295 natural compounds. The resultant 23 hits compounds with pharmacophore fit score 75.31 to 78.81 were optimized using in-silico ADMET and molecular docking analysis. Four potential natural inhibitory molecules namely D-DOPA (Amb17613565), L-Saccharopine (Amb6600091), D-Phenylalanine (Amb3940754), and L-Mimosine (Amb21855906) have been selected based on their binding affinity (-7.5, -7.1, -7.1, and -7.0 kcal/mol), respectively. Moreover, 250 ns molecular dynamics (MD) simulations confirmed the structural stability of the ligands within the protein. Additionally, MM/GBSA approach also used to support the stability of molecules to the binding site of the protein that also confirm the stability of the selected four natural compounds. The virtual screening strategy used in this study demonstrated four natural compounds that can be utilized for designing a future class of potential natural ACE2 inhibitor that will block the spike (S) protein dependent entry of SARS-CoV-2 into the host cell.

Summary Introduction: The main protease (Mpro) and the papain-like protease (PLpro) are essential for the replication of SARS-CoV-2. Both proteases can be targets for drugs acting against SARS-CoV-2. Objective: This paper aims to investigate the in silico activity of nine xanthophylls as inhibitors of Mpro and PLpro. Methods: The structures of Mpro (PDB-ID: 6LU7) and PLpro (PDB-ID: 6W9C) were obtained from RCSB Protein Data Bank and developed with BIOVIA Discovery Studio. Active sites of proteins were performed using CASTp. For docking the PyRx was used. Pharmacokinetic parameters of ADMET were evaluated using SwissADME and pkCSM. Results: β-cryptoxanthin exhibited the highest binding energy: –7.4 kcal/mol in the active site of Mpro. In PLpro active site, the highest binding energy had canthaxanthin of –9.4 kcal/mol, astaxanthin –9.3 kcal/mol, flavoxanthin –9.2 kcal/mol and violaxanthin –9.2 kcal/mol. ADMET studies presented lower toxicity of xanthophylls in comparison to ritonavir and ivermectin. Conclusion: Our findings suggest that xanthophylls can be used as potential inhibitors against SARS-CoV-2 main protease and papain-like protease.

Abstract Transporter associated with antigen processing 1 (TAP1) is a transporter protein that represent tumor antigen in the MHC I or HLA complex. Any defect in the TAP1 gene resulting in inadequate tumor tracking. TAP1 influences multidrug resistance (MDR) in human cancer cell lines and hinders the treatment during chemotherapeutic. The association of TAP1 in cancer progression remains mostly unknown and further study of the gene in relation with cancer need to conduct. Thus, the study has designed to analyze the association between the TAP1 with cancer by computationally. The expression pattern of the gene has determined by using ONCOMINE, GENT2, and GEPIA2 online platforms. The protein level of TAP1 was examined by the help of Human Protein Atlas. Samples with different clinical outcomes were investigated to evaluate the expression and promoter methylation in cancer vs. normal tissues by using UALCAN server. The copy number alteration, mutation frequency, and expression level of the gene in different cancer were analyzed by using cBioPortal server. The PrognoScan and KM plotter platforms were used to perform the survival analysis and represented graphically. Additionally, pathway and gene ontology (GO) features correlated to the TAP1 gene were analyzed and presented by bar charts. After arranging the data in a single panel like correlating expression to prognosis, mutational and alterations characteristic, and pathways analysis, we observed some interesting insights that emphasized the importance of the gene in cancer progression. The study found the relationship between the TAP1 expression pattern and prognosis in different cancer tissues and shows how TAP1 affects the clinical characteristics. The analytical data presented in the study is vital to learn about the effect of TAP1 in tumor tissue, where previously studies showing contradicting expression of TAP1 in cancer tissue. The analyzed data can also be utilized further to evade the threats against chemotherapy. Overall, the study provided a new aspect to consider the role of TAP1 gene in cancer progression and survival status. Key messages • This study demonstrated, for the first time, a correlation between the TAP1 gene and tumor progression. • An upregulation of TAP1 mRNA was demonstrated in various cancer types. • This study reported a significant negative correlation for TAP1 gene expression and the survival rate in different cancer types.

Nipah virus (NiV) is a zoonotic pathogen that causes Nipah encephalitis. it was thought to have transmitted from bats to pigs and ultimately to humans. Infected humans may experience an asymptomatic infection or mild to deadly symptoms. The coordinated actions of envelope attachment glycoprotein led to viral entry. NiV has been classified as a pandemic potential virus due to the lack of specialized vaccinations or treatments, as well as its high pathogenicity. In Computer-Aided Drugs Design study, active site prediction, ADMET properties, molecular docking assist to select five suitable small molecular compounds including control compound against NiV attachment glycoprotein(G) chain A to suppress its function. Binding affinity scores of selected compounds were distributed between -6.2 to -6.5 kcal/mol. All the selected compounds had desirable non-toxic and good pharmacokinetics properties. In Molecular Dynamic (MD) simulation, the ligands Amb33921182, Amb35795905, Amb22736116, and Amb28974637 are all potential drug candidates, but Amb33921182 is the most acceptable. This in-silico method has the potential to help with drug discovery and development in a short period of time against Nipah virus.

Long-term fungal infections that are difficult to treat require new substances for their prevention, treatment, or as adjuvants during antibiotic therapy. Propolis is a very promising source of natural substances that show a wide range of pharmacological properties, including antifungal activity against various fungal strains. The purpose of the literature review was to summarize recent studies (PubMed, Scopus) on progress in evaluating the antifungal activity of chemically defined propolis extracts. During the selection of studies, only those with results of antifungal activity expressed as minimal inhibitory concentration (MIC) and/or minimal fungicidal concentration (MFC) were analyzed. Moreover, plant, animal and environmental factors influencing the chemical composition of propolis are discussed. Mechanisms of antifungal activity of propolis extracts and research trends in the aspect of developing new therapies and the assessment of drug interactions are indicated. The review of the research results shows that there is great progress in the definition of propolis extracts. After comparing the MIC/MFC values, it was assessed that propolis extracts offer a wide range of activity not only against pathogenic Candida strains but also against risky molds; however, the strength of this activity is varied.

Colorectal cancer (CRC) is the second most common cause of death worldwide, affecting approximately 1.9 million individuals in 2020. Therapeutics of the disease are not yet available and discovering a novel anticancer drug candidate against the disease is an urgent need. Thymidylate synthase (TS) is an important enzyme and prime precursor for DNA biosynthesis that catalyzes the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) that has emerged as a novel drug target against the disease. Elevated expression of TS in proliferating cells promotes oncogenesis as well as CRC. Therefore, this study aimed to identify potential natural anticancer agents that can inhibit the activity of the TS protein, subsequently blocking the progression of colorectal cancer. Initially, molecular docking was implied on 63 natural compounds identified from

Astaxanthin (AST) and fucoxanthin (FUC) are natural xanthophylls, having multidirectional activity, including antioxidant, anti-inflammatory, and anticancer. Both compounds also show antimicrobial activity, which is presented in this review article. There are few papers that have presented the antimicrobial activity of AST. Obtained antimicrobial concentrations of AST (200–4000 µg/mL) are much higher than recommended by the European Food Safety Authority for consumption (2 mg daily). Therefore, we suggest that AST is unlikely to be of use in the clinical treatment of infections. Our knowledge about the antimicrobial activity of FUC is better and this compound acts against many bacteria already in low concentrations 10–250 µg/mL. Toxicological studies on animals present the safety of FUC application in doses 200 mg/kg body weight and higher. Taking available research into consideration, a clinical application of FUC as the antimicrobial substance is real and can be successful. However, this aspect requires further investigation. In this review, we also present potential mechanisms of antibacterial activity of carotenoids, to which AST and FUC belong.

SARS-CoV-2 is an etiologic agent responsible for the coronavirus disease 2019 (COVID-19) pandemic. The virus has rapidly extended globally and taken millions of lives due to the unavailability of therapeutics candidates against the virus. Till now, no specific drug candidates have been developed that can prevent or treat infections caused by the pathogen. The main protease (M

Angiotensin-converting enzyme 2 (ACE2), also known as peptidyl-dipeptidase A, belongs to the dipeptidyl carboxydipeptidases family has emerged as a potential antiviral drug target against SARS-CoV-2. Most of the ACE2 inhibitors discovered until now are chemical synthesis; suffer from many limitations related to stability and adverse side effects. However, natural, and selective ACE2 inhibitors that possess strong stability and low side effects can be replaced instead of those chemicals’ inhibitors. To envisage structurally diverse natural entities as an ACE2 inhibitor with better efficacy, a structure-based-pharmacophore model (SBPM) was developed and validated by 20 known selective inhibitors with their correspondence 1166 decoy compounds. The validated SBPM has excellent goodness of hit score and good predictive ability, which has been appointed as a query model for further screening of 11,295 natural compounds. The resultant 23 hits compounds with pharmacophore fit score 75.31 to 78.81 were optimized using in-silico ADMET and molecular docking analysis. Four potential natural inhibitory molecules namely D-DOPA (Amb17613565), L-Saccharopine (Amb6600091), D-Phenylalanine (Amb3940754), and L-Mimosine (Amb21855906) have been selected based onbinding affinity (−7.5, −7.1, −7.1, and −7.0 kcal/mol), respectively. Moreover, 250 ns molecular dynamics (MD) simulations confirmed the structural stability of the ligands within the protein. Additionally, MM/GBSA approach also used to support the stability of molecules to the binding site of the protein that also confirm the stability of the selected four natural compounds. The virtual screening strategy used in this study demonstrated four natural compounds that can be utilized for designing a future class of potential natural ACE2 inhibitor that will block the spike (S) protein dependent entry of SARS-CoV-2 into the host cell.

Minichromosome maintenance complex component 7 (MCM7) belongs to the minichromosome maintenance family that is important for the initiation of eukaryotic DNA replication. Overexpression of the MCM7 protein is relative to cellular proliferation and responsible for aggressive malignancy in various cancers. Mechanistically, inhibition of MCM7 significantly reduces the cellular proliferation associated with cancer. To date, no effective small molecular candidate has been identified that can block the progression of cancer induced by the MCM7 protein. Therefore, the study has been designed to identify small molecular-like natural drug candidates against aggressive malignancy associated with various cancers by targeting MCM7 protein. To identify potential compounds against the targeted protein a comprehensive in silico drug design including molecular docking, ADME (Absorption, Distribution, Metabolism and Excretion), toxicity, and molecular dynamics (MD) simulation approaches has been applied. Seventy phytochemicals isolated from the neem tree (Azadiractha indica) were retrieved and screened against MCM7 protein by using the molecular docking simulation method, where the top four compounds have been chosen for further evaluation based on their binding affinities. Analysis of ADME and toxicity properties reveals the efficacy and safety of the selected four compounds. To validate the stability of the protein–ligand complex structure MD simulations approach has also been performed to the protein–ligand complex structure, which confirmed the stability of the selected three compounds including CAS ID:105377-74-0, CID:12308716 and CID:10505484 to the binding site of the protein. In the study, a comprehensive data screening process has performed based on the docking, ADMET properties, and MD simulation approaches, which found a good value of the selected four compounds against the targeted MCM7 protein and indicates as a promising and effective human anticancer agent.

Introduction: Tragia involucrata L. have been utilized as traditional medicine in Indian subcontinent for the treatment of numerous illnesses such as inflammation, pain and skin infection. In this current study we sought to assess the anxiolytic, sedative and analgesic activity of Tragia involucrata L. leaves extract. Materials and methods: We first performed a phytochemical screening test of the leaves extracts following standard phytochemical screening protocols. We next examined the anxiolytic and sedative activity of crude methanol (TIME), ethyl acetate (TIEAE) and n-Hexane (TIHE) extract of Tragia involucrata L. leaves using mouse behavioral models such as elevated plus-maze test and pentobarbital-induced sleeping time test, respectively. Likewise, we evaluated the analgesic activity using acetic acid induced writhing test and formalin induced paw licking test. Additionally, we performed a quantitative analysis of heavy metals content of Tragia involucrata L. leaves by overnight digestion in concentrated nitric acid (HNO3). Results: Phytochemical screening demonstrated that TIME, TIEAE and TIHE contain flavonoids, alkaloids, tannins, phenols, terpenoids and sterols. Administration of these extracts resulted in higher number of open arm entry, lower number of close arm entry and higher time spent in open arm compared to control treatment (p < 0.05). Moreover, these treatments decreased the onset of sleep time and increased the duration of sleep compared to control treated mice (all p < 0.05). Likewise, extracts treated mice exhibited decreased number of writhing as well as lower acute phase and late phase duration compared to control treatment (all p < 0.05). The average level of As and Fe in Tragia involucrata L. leaves was 5.16 ± 0.012 ppm and 2.76 ± 0.015 ppm, respectively. Conclusion: Results from this study support that Tragia involucrata L. leaves extracts exhibit an anxiolytic, sedative and analgesic activity in mice.

Transporter associated with antigen processing 1 (TAP1) gene codes for a transporter protein, which is responsible for tumor antigen presentation in the MHC I or HLA complex. A defect in the gene results in an inadequate tumor tracking. TAP1 may also influence multi drug resistance, which is an extreme threat in providing treatment by drugs which are chemotherapeutic. The gene of TAP1 was analyzed bioinformatically. It gave us prognostic data as a confirmation of whether it should be used as a biomarker. The expression level and pattern analysis were conducted using ONCOMINE, GENT2 and GEPIA2 online platforms. Samples with different clinical outcomes were investigated for expression and promoter methylation analysis was done in cancer vs normal tissues using UALCAN. The copy number alteration and mutation frequency and expression in different cancer studies were analyzed using cBioPortal. The PrognoScan and KM plotter survival analysis of significant data (p-value

Bone morphogenetic protein 1 (BMP1) is a secreted metalloprotease of the astacin M12A family of bone morphogenetic proteins (BMPs). BMP1 activates transforming growth factor-β (TGF-β) and BMP signaling pathways by proteolytic cleavage, which has dual roles in gastrointestinal tumor development and progression.TGF-β promotes invasion and metastasis of gastric cancer (GC) by the help of BMP1, so upregulation of the BMP1 may increase cancer invasiveness in GC. In this study,the transcriptional expression, mutations, survival rate, TFs, miRNAs, gene ontology, and signaling pathways of BMP1 were analyzed by using different web servers. We found higher transcriptional and clinicopathological characteristics expression compared to normal tissues, worsening survival rate in GC. We detected 25 missenses, 15 truncating mutations, 23 TFs, and 8 miRNAs. Finally, we identified and analyzed the co-expressed genes and found that the leukemia inhibitory factor is the most positively correlated gene. The gene ontological features and signaling pathways involved in GC development were evaluated as well. We believe that this study will provide a basis for BMP1 to be a significant biomarker for human GC prognosis.

Ongoing COVID-19 outbreak has raised a drastic challenge to global public health security. Most of the patients with COVID-19 suffer from mild flu-like illnesses such as cold and fever; however, few percentages of the patients progress from severe illness to death, mostly in an immunocompromised individual. The causative agent of COVID-19 is an RNA virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite these debilitating conditions, no medication to stop the disease progression or vaccination is available till now. Therefore, we aimed to formulate a multi-epitope vaccine against SARS-CoV-2 by utilizing an immunoinformatics approach. For this purpose, we used the SARS-CoV-2 spike glycoprotein to determine the immunodominant T- and B-cell epitopes. After rigorous assessment, we designed a vaccine construct using four potential epitopes from each of the three epitope classes such as cytotoxic T-lymphocytes, helper T-lymphocyte, and linear B-lymphocyte epitopes. The designed vaccine was antigenic, immunogenic, and non-allergenic with suitable physicochemical properties and has higher solubility. More importantly, the predicted vaccine structure was similar to the native protein. Further investigations indicated a strong and stable binding interaction between the vaccine and the toll-like receptor (TLR4). Strong binding stability and structural compactness were also evident in molecular dynamics simulation. Furthermore, the computer-generated immune simulation showed that the vaccine could trigger real-life-like immune responses upon administration into humans. Finally, codon optimization based on Escherichia coli K12 resulted in optimal GC content and higher CAI value followed by incorporating it into the cloning vector pET28+(a). Overall, these results suggest that the designed peptide vaccine can serve as an excellent prophylactic candidate against SARS-CoV-2. Communicated by Ramaswamy H. Sarma

Introduction Tragia involucrata L. have been utilized as traditional medicine in Indian subcontinent for the treatment of numerous illnesses such as inflammation, pain and skin infection. In this current study we sought to assess the anxiolytic, sedative and analgesic activity of Tragia involucrata L. leaves extract. Materials and methods We first performed a phytochemical screening test of the leaves extracts following standard phytochemical screening protocols. We next examined the anxiolytic and sedative activity of crude methanol (TIME), ethyl acetate (TIEAE) and n-Hexane (TIHE) extract of Tragia involucrata L. leaves using mouse behavioral models such as elevated plus-maze test and pentobarbital-induced sleeping time test, respectively. Likewise, we evaluated the analgesic activity using acetic acid induced writhing test and formalin induced paw licking test. Additionally, we performed a quantitative analysis of heavy metals content of Tragia involucrata L. leaves by overnight digestion in concentrated nitric acid (HNO3). Results Phytochemical screening demonstrated that TIME, TIEAE and TIHE contain flavonoids, alkaloids, tannins, phenols, terpenoids and sterols. Administration of these extracts resulted in higher number of open arm entry, lower number of close arm entry and higher time spent in open arm compared to control treatment (p < 0.05). Moreover, these treatments decreased the onset of sleep time and increased the duration of sleep compared to control treated mice (all p < 0.05). Likewise, extracts treated mice exhibited decreased number of writhing as well as lower acute phase and late phase duration compared to control treatment (all p < 0.05). The average level of As and Fe in Tragia involucrata L. leaves was 5.16 ± 0.012 ppm and 2.76 ± 0.015 ppm, respectively. Conclusion Results from this study support that Tragia involucrata L. leaves extracts exhibit an anxiolytic, sedative and analgesic activity in mice., Tragia involucrata L.; Phytochemical screening; Anxiolytic; Sedative; Analgesic and heavy metal study

P-type transport ATPase’s are active transporters that dispense the majority of the cellular functions. ATP13A2 have a role in neurodegeneration which is commonly associated with lysosomal dysfunction. Lysosome plays a significant role in the metabolism, secretion, signaling, plasma membrane repair, and autophagy which have fundamental implications in different carcinomas. ATP13A2 is placed in the lysosome and the late endosome and the drastic dysfunction in the lysosome is caused from its mutation. However, this systematic study was done to evaluate ATP13A2 as the possible prognostic marker for the glioblastoma multiform (GBM) is the utmost frequent primary cancer of the central nervous system. Within this cumulative study, we have inspected the pattern of expression of ATP13A2 and their corresponding outcome in GBM patients using different available databases. We examined a comparative study of ATP13A2 expression between the normal tissues and their cancers using the UALCAN, Oncomine, GEPIA2, and GENT2 databases. Both analyses showed significantly high ATP13A2 mRNA and protein expression in GBM than those of normal tissues. We investigate clinicopathological expression and methylation characteristics of GBM using UALCAN database, which analysis showed clinicopathological expression of ATP13A2 was down regulated and methylation was over-expressed in GBM compared to normal tissues. We also investigate mutations and the alterations of copy number of ATP13A2 using a database called cBioPortal, which showing about 5 (0.2%) alteration and 0.6% mutation frequency and co-expression profile through the Oncomine. We used the Enricher tool to predict the signaling pathways in GBM through gene ontology and pathway analysis of co-expressed genes. The PrognoScan analysis revealed that the increased ATP13A2 expression correlates with worse patient survival. Finally, our derived data apprises that, ATP13A2 may serve as a potential biomarker of GBM/brain cancer patients.

Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly infectious zoonotic virus first reported into the human population in September 2012 on the Arabian Peninsula. The virus causes severe and often lethal respiratory illness in humans with an unusually high fatality rate. The N-terminal domain (NTD) of receptor-binding S1 subunit of coronavirus spike (S) proteins can recognize a variety of host protein and mediates entry into human host cells. Blocking the entry by targeting the S1-NTD of the virus can facilitate the development of effective antiviral drug candidates against the pathogen. Therefore, the study has been designed to identify effective antiviral drug candidates against the MERS-CoV by targeting S1-NTD. Initially, a structure-based pharmacophore model (SBPM) to the active site (AS) cavity of the S1-NTD has been generated, followed by pharmacophore-based virtual screening of 11,295 natural compounds. Hits generated through the pharmacophore-based virtual screening have re-ranked by molecular docking and further evaluated through the ADMET properties. The compounds with the best ADME and toxicity properties have been retrieved, and a quantum mechanical (QM) based density-functional theory (DFT) has been performed to optimize the geometry of the selected compounds. Three optimized natural compounds, namely Taiwanhomoflavone B (Amb23604132), 2,3-Dihydrohinokiflavone (Amb23604659), and Sophoricoside (Amb1153724), have exhibited substantial docking energy &gt, −9.00 kcal/mol, where analysis of frontier molecular orbital (FMO) theory found the low chemical reactivity correspondence to the bioactivity of the compounds. Molecular dynamics (MD) simulation confirmed the stability of the selected natural compound to the binding site of the protein. Additionally, molecular mechanics generalized born surface area (MM/GBSA) predicted the good value of binding free energies (ΔG bind) of the compounds to the desired protein. Convincingly, all the results support the potentiality of the selected compounds as natural antiviral candidates against the MERS-CoV S1-NTD.

Breast cancer (BC) is the most common type of invasive cancer diagnosed in women. It is the second leading cause of death from cancer and the utmost important medical concern women face today. Growth differentiation factor 10 (GDF10) is a member of the transforming growth factor β (TGF-β) superfamily and has been found to play a central role during the growth and differentiation of developing tissues. Recent studies have demonstrated the linkage between GDF10 and different types of cancer. But the relation of GDF10 expression in developing BC has not been established with concrete evidence. Therefore, we performed a multi-omics analysis to evaluate the potentiality of GDF10 as a therapeutic biomarker for human BC. We analyzed the mRNA expression patterns of GDF10 in BC subtypes using Oncomine, GEPIA2, immunohistochemistry, and UALCAN databases. Resultant data obtained from the analysis has provided clear evidence to the downregulation of GDF10 expression in BC subtypes. Additionally, three subsequent missense mutations were identified with a frequency of 0.62%–2.95% copy number alterations in the GDF10 protein sequence by analyzing 16 BCE studies from the cBioPortal database. Furthermore, the Kaplan-Meier plots revealed a positive correlation between the downregulation of GDF10 and the lower survival rate of the BC patients. The co-expressed genes profile of GDF10 was also associated with BC development. ABCA8 has been identified as the most positively co-expressed gene, which was confirmed by correlation analysis using bc-GenExMiner and UCSC Xena server. We also determined different cancer progression pathways mediated by GDF10 and its co-expressed genes by utilizing the Enrichr database. Cumulatively, the outcome data conclude that the down expression of GDF10 is associated with BC progression and patient's survival, which may serve as a therapeutic biomarker for treating BC.

Increasing dependency on pharmaceutical compounds including antibiotics, analgesics, antidepressants, and other drugs has threatened the environment as well as human health. Their occurrence, transformation, and fate in the environment are causing significant concerns. Several existing treatment technologies are there with their pros and cons for the treatment of pharmaceutical wastewater (PWW). Still, electrocoagulation is considered as the modern and decisive technology for treatment. In the EC process, utilizing electricity (AC/DC) and electrodes, contaminants become coagulated with the metal hydroxide and are separated by co-precipitation. The main mechanism is charge neutralization and adsorption of contaminants on the generated flocs. The range of parameters affects the EC process and is directly related to the removal efficiency and its overall operational cost. This process only could be scaled up on the industrial level if process parameters become optimized and energy consumption is reduced. Unfortunately, the removal mechanism of particular pharmaceuticals and complex physiochemical phenomena involved in this process are not fully understood. For this reason, further research and reviews are required to fill the knowledge gap. This review discusses the use of EC for removing pharmaceuticals and focuses on removal mechanism and process parameters, the cost assessment, and the challenges involved in mitigation.

Conventionally treated wastewater disposal is a challenging task especially for developing countries as nutrients and some organic matters remain present in the effluent. A controlled floating pond is a suitable option for tropical countries such as India to reduce nutrients and untreated organic matters. In this study, three different locally available aquatic plant species were taken to cultivate in wastewater effluent and their respective growth and nutrients removal efficiency were compared. The three plants namely, Water Hyacinth (Eichhornia crassipes), Duckweeds (Lemna minor), Filamentous algae were cultivated in three identical tubs, with a depth of 20 cm, having 12L wastewater effluent. The growth parameter of plants and wastewater quality parameters was investigated at the interval of five days for 30 days. It was found that duckweeds are more effective in the removal of TKN by 37.67%, N-NO3 − by 83.33%, and N-NO2 - by 35.33%. On the other hand, filamentous algae were found more effective in the removal of COD by 49.36% and PO4 3− by 57.18%. The results from this study will assist in the selection of plants species for aquatic ponds based on the required treatment.

Breast cancer ranked second among most frequent cancer in the world playing a significant role in mortality rate. Having prior knowledge on differentially expressed genes in breast cell carcinoma elucidated important indications to understand the molecular mechanism underneath breast carcinogenesis. In this study we have investigated the distinguished CSN1S1 expression in human breast cancer. We have analyzed CSN1S1 mRNA expression between cancer and normal tissues using TCGA datasets. Moreover, analysis including promoter methylation, mutations, prognosis, co-expression, gene ontology, and pathways of CSN1S1 were performed by the TCGA Wanderer, UCSC Xena, cBioPortal, PrognoScan, UALCAN, and Enricher server. We have observed low mRNA expression and high promoter methylation of CSN1S1 in cancer tissues compared to normal tissues. Furthermore, we have also identified low mRNA expression in clinicopathological patients, as well as 9 deleterious mutations with highly co-expressed protein MRC1, and significantly related signaling pathways. We have found a positive correlation between the lower expression of CSN1S1 and patients surviving with breast cancer. Here we have concluded that CSN1S1 acts as a biomarker for the surveillance and prognosis of breast cancer, and also works as a novel therapeutic target at the molecular and pathway levels., Highlights • Low transcriptional expression and low survival rate of CSN1S1 in breast cancer. • The investigation of clinical profiles and mutational positions of CSN1S1 in breast cancer. • The investigation of gene ontology and signaling pathway of CSN1S1 and their co-expressed genes. • We identified CSN1S1 and also their co-expressed proteins are the potential biomarkers in breast cancer.

Minichromosome maintenance protein 2 (MCM2) is a highly conserved protein from the MCM protein family that plays an important role in eukaryotic DNA replication as well as in cell cycle progression. In addition, it maintains the ploidy level consistency in eukaryotic cells, hence, mutations or alteration of this protein could result in the disintegration of the fine-tuned molecular machinery that can lead to uncontrolled cell proliferation. Moreover, MCM2 has been found to be an important marker for progression and prognosis in different cancers. Therefore, we aimed to analyze the MCM2 expression and the associated outcome in breast cancer (BC) patients based on the publicly available online databases. In this study, server-based gene expression analyses indicate the upregulation of MCM2 (p < 10−6; fold change>2.0) in various BC subtypes as compared to the respective normal tissues. Besides, the evaluation of histological sections from healthy and cancer tissues showed strong staining signals indicating higher expression of MCM2 protein. The overexpression of MCM2 was significantly correlated to promoter methylation and was related to patients' clinical features. Further, mutation analysis suggested missense as the predominant type of mutation (71.4%) with 18 copy-number alterations and 0.2% mutation frequency in the MCM2 gene. This study revealed a significant correlation (Cox p ≤ 0.05) between the higher MCM2 expression and lower patient survival. Finally, we identified the co-expressed genes with gene ontological features and signaling pathways associated in BC development. We believe that this study will provide a basis for MCM2 to be a significant biomarker for human BC prognosis., Data analysis; Information retrieval; Computational chemistry; Computational biology; Bioinformatics; Biocomputational method; Gene expression; Gene mutation; Gene regulation; Microarray; Cancer research; MCM2; Breast cancer; Mutation analysis; Prognostic biomarker; Transcriptional expressions

Background: Rift Valley fever virus (RVFV) is an emerging arbovirus infecting both animals and humans. Any form of direct contact with body fluids, blood or tissue of infected animals is the mode of transmission of this pathogen. Despite being an emerging virus, no proper vaccinations are yet available for the public. Our objective is to compose a multiepitope vaccine utilizing immuno-bioinformatics as a strategy against RVFV. Methods: To identify immunodominant epitopes and design a potent vaccine candidate, we applied a series of immunoinformatic approaches with molecular dynamics and immune response simulation frameworks. Results: A glycoprotein with the highest antigenicity was selected and employed for determining promising epitopes. We selected T cell epitopes based on their immunological potencies and cytokine inducing properties, while B cell epitopes were selected based on their antigenic features. Finally, we selected four cytotoxic T-lymphocyte, two helper T-lymphocyte, and three linear B-lymphocyte epitopes that were arranged into a vaccine construct with appropriate adjuvants and linkers. The chimera protein was modeled, refined, and validated prior to docking against toll-like receptor 4. Docking studies suggest strong binding interactions while dynamics simulation revealed the stable nature of the docked complex. Furthermore, the immune simulation showed robust and prolonged immune responses with rapid antigen clearance. Finally, codon optimization and cloning conducted with Escherichia coli K12 suggests high translation efficiency within the host system. Conclusion: We believe that our designed multiepitope vaccine is a promising prophylactic candidate against RVFV pathogenesis.