Search results for: antiviral

Authors: Howaida I. Abd-Alla, Amal Z. Hassan, Maha Soltan, Atef G. Hanna, Mounir M. El-Safty

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Acokanthera oblongifolia (Apocynaceae) is used for treatment of several infection diseases and is a well-known cardiac glycoside-containing plant. The infusion of their leaves is gargled to treat tonsillitis and is used medicinally to treat snakebites. The total cardiac glycosides content in the leaves was determined by referring to gitoxigenin as a reference compound. Two triterpenes, lup-20(29)-en-3β-ol (1) and oleanolic acid (2); two cardenolides, acovenoside A (3) and acobioside A (4) were isolated from the ethyl acetate extract. Their structures were determined on the basis of spectral analysis. Major constituents isolated from this species were evaluated for cytotoxicity against normal lung cell line (Wi38) and antimicrobial activities against Gram-positive (two strains) and Gram-negative bacteria (four strains), yeast-like fungi (two strains) and fungi (five strains). The minimum inhibitory concentration (MIC) of the compounds was determined using broth microdilution method. Their viral inhibitory effects against avian influenza virus type A (AI-H5N1) and Newcastle disease virus (NDV) in specific pathogen free (SPF) embryonated chicken eggs (ECE), chicken embryo fibroblasts (CEF) and Vero cells were evaluated. The cardenolide (3) showed viral inhibitory effects against AI-H5N1 and NDV in SPF ECE. The two cardenolides isolated have shown potent cytotoxicity against Vero cells. Compound (3) showed potent anti-Gram-negative bacteria activity. These results suggested that acovenoside A might be promising for future antiviral and antimicrobial drug design.

Keywords: Acokanthera, AI-H5N1, Cardenolides, NDV, SPF-ECE, VERO, Wi38 , Microbe

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Authors: Tabassum Yasmin, Hamid Pahlevan

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HIV/Hepatitis C co-infection treatments have evolved substantially and they have similar sustained virologic response rates as those of Hepatitis C monoinfected population. There are a few studies on therapy of patients with dual genotypes, especially in HIV/Hepatic C coinfected group. Most studies portrayed case reports of dual genotype chronic Hepatitis C coinfection treatment with Sofosbuvir/Ledipasvir and Ribavirin. A 79-year-old male with a history of HIV on Truvada and Isentress had chronic Hepatitis C with 1a and 2 genotypes. The patient has a history of alcohol intake for 40 years but recently stopped drinking alcohol. He has a history of intravenous drug use in the past and currently is not using any recreational drugs. Patient has Fibro score of 0.7 with Metavir score F2 to F4. AFP is 3.2. The HCV RNA is 493,034 IU/ML. The HBV viral DNA is < 1.30 (not detected). The CD4 is 687CU/MM. The FIB 4 is 3.34 with APRI index 0.717. The HIV viral load is 101 copies/ML. MRI abdomen did not show any liver abnormality. Fixed dose Sofosbuvir/Ledipasvir was used for therapy without Ribavirin. He tolerated medication except for some minor gastrointestinal side effects like abdominal bloating. He demonstrated 100% adherence rate. Patient completed 12 weeks of therapy. HCV RNA was undetectable at 4 and 12 weeks. He achieved SVR at week 12 and subsequently had undetectable RNA for 2 years. Dual genotype prevalence in chronic hepatitis C population is rare, especially in HIV/hepatic coinfection. Our case demonstrates that dual genotypic cases can still be successfully treated with Direct Acting Antiviral agents. The newer agents for therapy for pan genotypes were not available at the time the patient was being treated. We demonstrated that dual agent therapy was still able to maintain SVR in our patient.

Keywords: HIV/Hepatitis C, SVR (sustained virologic response), DAA (direct active antiviral agents, dual genotype

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Authors: B. B. S. Pereira, M. O. Souza, L. P. Zanetti, L. C. S. Oliveira, J. R. P. Moreno, M. P. Souza, V. R. Colturato, C. M. Machado

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Background: The introduction of prophylactic or preemptive therapies has effectively decreased the CMV mortality rates after hematopoietic stem cell transplantation (HSCT). CMV antigenemia (pp65) or quantitative PCR are methods currently approved for CMV surveillance in pre-emptive strategies. Commercial assays are preferred as cut-off levels defined by in-house assays may vary among different protocols and in general show low reproducibility. Moreover, comparison of published data among different centers is only possible if international standards of quantification are included in the assays. Recently, the World Health Organization (WHO) established the first international standard for CMV detection. The real time PCR COBAS Ampliprep/ CobasTaqMan (CAP/CTM) (Roche®) was developed using the WHO standard for CMV quantification. However, the cut-off for the introduction of antiviral has not been determined yet. Methods: We conducted a retrospective study to determine: 1) the sensitivity and specificity of the new CMV CAP/CTM test in comparison with pp65 antigenemia to detect episodes of CMV infection/reactivation, and 2) the cut-off of viral load for introduction of ganciclovir (GCV). Pp65 antigenemia was performed and the corresponding plasma samples were stored at -20°C for further CMV detection by CAP/CTM. Comparison of tests was performed by kappa index. The appearance of positive antigenemia was considered the state variable to determine the cut-off of CMV viral load by ROC curve. Statistical analysis was performed using SPSS software version 19 (SPSS, Chicago, IL, USA.). Results: Thirty-eight patients were included and followed from August 2014 through May 2015. The antigenemia test detected 53 episodes of CMV infection in 34 patients (89.5%), while CAP/CTM detected 37 episodes in 33 patients (86.8%). AG and PCR results were compared in 431 samples and Kappa index was 30.9%. The median time for first AG detection was 42 (28-140) days, while CAP/CTM detected at a median of 7 days earlier (34 days, ranging from 7 to 110 days). The optimum cut-off value of CMV DNA was 34.25 IU/mL to detect positive antigenemia with 88.2% of sensibility, 100% of specificity and AUC of 0.91. This cut-off value is below the limit of detection and quantification of the equipment which is 56 IU/mL. According to CMV recurrence definition, 16 episodes of CMV recurrence were detected by antigenemia (47.1%) and 4 (12.1%) by CAP/CTM. The duration of viremia as detected by antigenemia was shorter (60.5% of the episodes lasted ≤ 7 days) in comparison to CAP/CTM (57.9% of the episodes lasting 15 days or more). This data suggests that the use of antigenemia to define the duration of GCV therapy might prompt early interruption of antiviral, which may favor CMV reactivation. The CAP/CTM PCR could possibly provide a safer information concerning the duration of GCV therapy. As prolonged treatment may increase the risk of toxicity, this hypothesis should be confirmed in prospective trials. Conclusions: Even though CAP/CTM by ROCHE showed great qualitative correlation with the antigenemia technique, the fully automated CAP/CTM did not demonstrate increased sensitivity. The cut-off value below the limit of detection and quantification may result in delayed introduction of pre-emptive therapy.

Keywords: antigenemia, CMV COBAS/TAQMAN, cytomegalovirus, antiviral cut-off

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Authors: Amalia Ardeljan, Lexi Frankel, Divesh Manjani, Gabriela Santizo, Maximillian Guerra, Omar Rashid

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Introduction: Cytomegalovirus (CMV) infection is a widespread infection affecting between 60-70% of people in industrialized countries. CMV has been previously correlated with a higher incidence of Hodgkin Lymphoma compared to noninfected persons. Research regarding prior CMV infection and subsequent lymphoma development is still controversial. With limited evidence, further research is needed in order to understand the relationship between previous CMV infection and subsequent lymphoma development. This study assessed the effect of CMV infection and the incidence of lymphoma afterward. Methods: A retrospective cohort study (2010-2019) was conducted through a Health Insurance Portability and Accountability Act (HIPAA) compliant national database and conducted using International Classification of Disease (ICD) 9th,10th codes, and Current Procedural Terminology (CPT) codes. These were used to identify lymphoma diagnosis in a previously CMV infected population. Patients were matched for age range and Charlson Comorbidity Index (CCI). A chi-squared test was used to assess statistical significance. Results: A total number of 14,303 patients was obtained in the CMV infected group as well as in the control population (matched by age range and CCI score). Subsequent lymphoma development was seen at a rate of 11.44% (1,637) in the CMV group and 5.74% (822) in the control group, respectively. The difference was statistically significant by p= 2.2x10-16, odds ratio = 2.696 (95% CI 2.483- 2.927). In an attempt to stratify the population by antiviral medication exposure, the outcomes were limited by the decreased number of members exposed to antiviral medication in the control population. Conclusion: This study shows a statistically significant correlation between prior CMV infection and an increased incidence of lymphoma afterward. Further exploration is needed to identify the potential carcinogenic mechanism of CMV and whether the results are attributed to a confounding bias.

Keywords: cytomegalovirus, lymphoma, cancer, microbiology

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Authors: Amirah Azzeri, Fatiha H. Shabaruddin, Scott A. McDonald, Rosmawati Mohamed, Maznah Dahlui

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Objective: A scaled-up treatment cascade with direct-acting antiviral (DAA) therapy is necessary to achieve global WHO targets for hepatitis C virus (HCV) elimination in Malaysia. Recently, limited access to Sofosbuvir/Daclatasvir (SOF/DAC) is available through compulsory licensing, with future access to Sofosbuvir/Velpatasvir (SOF/VEL) expected through voluntary licensing due to recent agreements. SOF/VEL has superior clinical outcomes, particularly for cirrhotic stages, but has higher drug acquisition costs compared to SOF/DAC. It has been proposed that a stratified treatment cascade might be the most cost-efficient approach for Malaysia whereby all HCV patients are treated with SOF/DAC except for patients with cirrhosis who are treated with SOF/VEL. This study aimed to conduct a five-year budget impact analysis from the provider perspective of the proposed stratified treatment cascade for HCV treatment in Malaysia. Method: A disease progression model that was developed based on model-predicted HCV epidemiology data in Malaysia was used for the analysis, where all HCV patients in scenario A were treated with SOF/DAC for all disease stages while in scenario B, SOF/DAC was used only for non-cirrhotic patients and SOF/VEL was used for the cirrhotic patients. The model projections estimated the annual numbers of patients in care and the numbers of patients to be initiated on DAA treatment nationally. Healthcare costs associated with DAA therapy and disease stage monitoring was included to estimate the downstream cost implications. For scenario B, the estimated treatment uptake of SOF/VEL for cirrhotic patients were 25%, 50%, 75%, 100% and 100% for 2018, 2019, 2020, 2021 and 2022 respectively. Healthcare costs were estimated based on standard clinical pathways for DAA treatment described in recent guidelines. All costs were reported in US dollars (conversion rate US$1=RM4.09, the price year 2018). Scenario analysis was conducted for 5% and 10% reduction of SOF/VEL acquisition cost anticipated from the competitive market pricing of generic DAA in Malaysia. Results: The stratified treatment cascade with SOF/VEL in Scenario B was found to be cost-saving compared to Scenario A. A substantial portion of the cost reduction was due to the costs associated with DAA therapy which resulted in USD 40 thousand (year 1) to USD 443 thousand (year 5) savings annually, with cumulative savings of USD 1.1 million after 5 years. Cost reductions for disease stage monitoring were seen in year three onwards which resulted in cumulative savings of USD 1.1 thousand. Scenario analysis estimated cumulative savings of USD 1.24 to USD 1.35 million when the acquisition cost of SOF/VEL was reduced. Conclusion: A stratified treatment cascade with SOF/VEL was expected to be cost-saving and can results in a budget impact reduction in overall healthcare expenditure in Malaysia compared to treatment with SOF/DAC. The better clinical efficacy with SOF/VEL is expected to halt patients’ HCV disease progression and may reduce downstream costs of treating advanced disease stages. The findings of this analysis may be useful to inform healthcare policies for HCV treatment in Malaysia.

Keywords: Malaysia, direct acting antiviral, compulsory licensing, voluntary licensing

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Authors: Howaida I. Abd-Alla, Omnia Kutkat, Yassmin Moatasim, Magda T. Ibrahim, Marwa A. Mostafa, Mohamed GabAllah, Mounir M. El-Safty

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Artemisia judaica (known shih-balady), Azadirachta indica and Sophora tomentosa (known yellow necklace pod) are members of available medicinal plants well-known for their traditional medical use in Egypt which suggests that they probably harbor broad-spectrum antiviral, immunostimulatory and anti-inflammatory functions. Their ethyl acetate-dichloromethane (1:1, v/v) extracts were evaluated for the potential anti-Middle East respiratory syndrome-related coronavirus (anti-MERS-CoV) activity. Their cytotoxic activity was tested in Vero-E6 cells using 3-(4,-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method with minor modification. The plot of percentage cytotoxicity for each extract concentration has calculated the concentration which exhibited 50% cytotoxic concentration (TC50). A plaque reduction assay was employed using safe dose of extract to evaluate its effect on virus propagation. The highest inhibition percentage was recorded for the yellow necklace pod, followed by Shih-balady. The possible mode of action of virus inhibition was studied at three different levels viral replication, viral adsorption and virucidal activity. The necklace pod leaves have induced virucidal effects and direct effects on the replication of virus. Phytochemical investigation of the promising necklace pod led to the isolation and structure determination of nine compounds. The structure of each compound was determined by a variety of spectroscopic methods. Compounds 4-O-methyl sorbitol 1, 8-methoxy daidzin 6 and 6-methoxy apigenin-7-O-β-D-glucopyranoside 8 were isolated for the first time from the Sophora genus and the other six compounds were the first time that they were isolated from this species according to available works of literature. Generally, the highest anti-CoV 2 activity of S. tomentosa was associated with the crude ethanolic extract, indicating the possibility of synergy among the antiviral phytochemical constituents (1-9).

Keywords: coronavirus, MERS-CoV, mode of action, necklace pod, shih-balady

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Authors: Sajewicz-Krukowska Joanna, Domańska-Blicharz Katarzyna, Tarasiuk Karolina, Marzec-Kotarska Barbara

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Astroviral infections pose a significant problem in the poultry industry, leading to multiple adverse effects such as decreased egg production, breeding disorders, poor weight gain, and even increased mortality. Commonly observed chicken astrovirus (CAstV) was recently reported to be responsible for "white chicks syndrome" associated with increased embryo/chick mortality. The CAstV-mediated pathogenesis in chicken occurs due to complex interactions between the infectious pathogen and the immune system. Many aspects of CAstV-chicken interactions remain unclear, and there is no information available regarding gene expression changes in the chicken's spleen in response to CAstV infection. We aimed to investigate the molecular background triggered by CAstV infection. Ten 21-day-old SPF White Leghorn chickens were divided into two groups of 5 birds each. One group was inoculated with CAstV, and the other was used as the negative control. On 4th dpi, spleen samples were collected and immediately frozen at -70°C for RNA isolation. We analysed transcriptional profiles of the chickens' spleens at the 4th day following infection using RNA-seq to establish differentially expressed genes (DEGs). The RNA-seq findings were verified by quantitative real-time PCR (qRT-PCR). A total of 31959 transcripts were identified in response to CAstV infection. Eventually 45 DEGs (p-value<0.05; Log2Foldchange>1)were recognized in the spleen after CAstV infection (26 upregulated DEGs and 19 downregulated DEGs). qRT-PCR performed on 4 genes (IFIT5, OASL, RASD1, DDX60) confirmed RNAseq results. Top differentially expressed genes belonged to novel putative IFN-induced CAstV restriction factors. Most of the DEGs were associated with RIG-I–like signalling pathway or, more generally, with an innate antiviral response(upregulated: BLEC3, CMPK2, IFIT5, OASL, DDX60, IFI6, and downregulated: SPIK5, SELENOP, HSPA2, TMEM158, RASD1, YWHAB). The study provided a global analysis of host transcriptional changes that occur during CAstV infection in vivo and proved the cell cycle in the spleen and immune signalling in chickens were predominantly affected upon CAstV infection.

Keywords: chicken astrovirus, CastV, RNA-seq, transcriptome, spleen

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Authors: Restu Misrianti

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The amino acid variation of Asn (allele A) at position 631 in Mx gene was specific to positive antiviral to avian viral desease. This research was aimed at identifying polymorphism of Mx gene in duck using molecular technique. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) technique was used to select the genotype of AA, AG and GG. There were thirteen duck from Indragiri Hulu regency (Riau Province) used in this experiment. DNA amplification results showed that the Mx gene in duck is found in a 73 bp fragment. Mx gene in duck did not show any polymorphism. The frequency of the resistant allele (AA) was 0%, while the frequency of the susceptible allele (GG) was 100%.

Keywords: duck, Mx gene, PCR, RFLP

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Authors: Yasser Ahmed Mahmoud Ali Helal

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The use of CAD (Computer Aided Design) technology is ubiquitous in the architecture, engineering and construction (AEC) industry. This has led to its inclusion in the curriculum of architecture schools in Nigeria as an important part of the training module. This article examines the ethical issues involved in implementing CAD (Computer Aided Design) content into the architectural education curriculum. Using existing literature, this study begins with the benefits of integrating CAD into architectural education and the responsibilities of different stakeholders in the implementation process. It also examines issues related to the negative use of information technology and the perceived negative impact of CAD use on design creativity. Using a survey method, data from the architecture department of University was collected to serve as a case study on how the issues raised were being addressed. The article draws conclusions on what ensures successful ethical implementation. Millions of people around the world suffer from hepatitis C, one of the world's deadliest diseases. Interferon (IFN) is treatment options for patients with hepatitis C, but these treatments have their side effects. Our research focused on developing an oral small molecule drug that targets hepatitis C virus (HCV) proteins and has fewer side effects. Our current study aims to develop a drug based on a small molecule antiviral drug specific for the hepatitis C virus (HCV). Drug development using laboratory experiments is not only expensive, but also time-consuming to conduct these experiments. Instead, in this in silicon study, we used computational techniques to propose a specific antiviral drug for the protein domains of found in the hepatitis C virus. This study used homology modeling and abs initio modeling to generate the 3D structure of the proteins, then identifying pockets in the proteins. Acceptable lagans for pocket drugs have been developed using the de novo drug design method. Pocket geometry is taken into account when designing ligands. Among the various lagans generated, a new specific for each of the HCV protein domains has been proposed.

Keywords: drug design, anti-viral drug, in-silicon drug design, hepatitis C virus (HCV) CAD (Computer Aided Design), CAD education, education improvement, small-size contractor automatic pharmacy, PLC, control system, management system, communication

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Authors: Ewa Flaczyk, Monika Przeor, Joanna Kobus-Cisowska, Józef Korczak

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The aim of this paper was to collect the information concerning the most popular raw plant materials of antidiabetic activity, in a context of functional food developing production. The elaboration discusses morphological elements possible for an application in functional food production of the plants such as: common bean, ginger, Ceylon cinnamon, white mulberry, fenugreek, French lilac, ginseng, jambolão, and bitter melon. An activity of bioactive substances contained in these raw plant materials was presented, pointing their antiglycemic and also hypocholesterolemic, antiarthritic, antirheumatic, antibacterial, and antiviral activity in the studies on humans and animals. Also the genesis of functional food definition was presented.

Keywords: antiglycemic activity, raw plant materials, functional food, food, nutritional sciences

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Authors: Hassina Harkat, Samiha Taybe, Salima Loucif, Valérie Beneteau, Patrick Pale

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Indole and its derivatives have attracted great interest because of their importance in the synthetic organic and medicinal chemistry. They are widely used as anti hypertension, anti tubercular, anticancer activity, antiviral, Alzheimer's disease, antioxidant properties, and free radical induced lipid peroxidation. Many drugs and natural products contain indole moiety, such as the vinca alkaloids, fungal metabolites and marine natural products. Generally applicable synthetic methods for indole moiety involve ring closure to form the pyrrole. Indole derivatives can also be accessed by further functionalization of the indole nucleus. Therefore we report a mild and efficient protocol for the synthesis of analogues of indole catalyzed via zeolithe USY doped with CuI under solvent-free conditions.

Keywords: indole, zeolithe, USY-CuI, heterogeneous catalysis

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Authors: Özlem Arpacı, Zeliha Soysal, Nuran Diril

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Benzoxazoles are heterocyclic compounds that have a fused benzene and an oxazole ring. These heterocyclic compounds are reported to have antibacterial, antitubercular, antifungal, antiviral, antioxidant and anticancer activities. In this study, some benzoxazole derivatives that have broad antimicrobial and potent antitumoral activities, are investigated their mutagenic activities with using the Ames Test. The Ames test was conducted using Salmonella typhimurium TA98, TA100 and TA102 tester strains in the standard plate incorporation assay in the absence of liver S9 fraction. The results are evaluated using SPSS and none of the benzoxazole derivatives showed mutagenic activity using the Ames test in the absence of S9 liver fraction.

Keywords: benzoxazoles, ames test, mutagenic activity, antimutagenic activity, antitumoral activity

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Authors: Emel Yildiz, Nurcan Biçer, Fazilet Aksu, Arash Alizadeh Yegani

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Plants provide the wealth of bioactive compounds, which exert a substantial strategy for the treatment of neurological disorders such as Alzheimer's disease. Recently, a lot of studies have explored the medicinal properties of curcumin, including antitumoral, antimicrobial, anti-inflammatory, antioxidant, antiviral, and anti-Alzheimer's disease effects. Metal complexes of curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) were synthesized with Mn(II) and Fe(III). The structures of synthesized metal complexes have been characterized by using spectroscopic and analytic methods such as elemental analysis, magnetic susceptibility, FT-IR, AAS, TG and argentometric titration. It was determined that the complexes have octahedral geometry. The effects of the metal complexes on the disorder of memory, which is an important symptom of Alzheimer's Disease were studied on lab rats with Plus-Maze Tests at Behavioral Pharmacology Laboratory.

Keywords: curcumin, Mn(II), Fe(III), Alzheimer disease, beta amyloid 25-35

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Authors: Rajesh A. Rane, Shital S. Naphade, Rajshekhar Karpoormath

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Thiozolidin-4-one, a mimic of thiazolobenzimidazole (TBZ) has drawn many attentions due to its potent and selective inhibition against the HIV-1 and low toxicity by binding to the allosteric site of the reverse transcriptase (RT) as a non-nucleoside RT inhibitor (NNRTI). Similarly, marine bromopyrrole alkaloids are well known for their diverse array of anti-infective properties. Hence, we have reported synthesis and in vitro HIV-1 RT inhibitory activity of a series of 4-thiazolidinone-bromopyrrole alkaloid hybrids tethered with amide linker. The results of in vitro HIV-1 RT kit assay showed that some of the compounds, such as 4c, 4d, and 4i could effectively inhibit RT activity. Among them, compounds 4c having 4-chlorophenyl substituted 4-thiazolidione ring was the best one with the IC50 value of 0.26 µM. The sturdy emerges with key structure-activity relationship that pyrrole-NH-free core benefited inhibition against HIV-1 RT inhibition. This study identified conjugate 4c with potent activity and selectivity as promising compound for further drug development to HIV.

Keywords: antiviral drugs, bromopyrrole alkaloids, HIV-1 RT inhibition, 4-thiazolidinone

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Authors: K. Domagala, D. Kata, T. Graule

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Diseases caused by contaminated drinking water are the worldwide problem, which leads to the death and severe illnesses for hundreds of millions million people each year. There is an urgent need for efficient water treatment techniques for virus pathogens removal. The aim of the research was to develop safe and economic solution, which help with the water treatment. In this study, the synthesis of copper-based multi-walled carbon nanotube composites is described. Proposed solution utilize combination of a low-cost material with a high active surface area and copper antiviral properties. Removal of viruses from water was possible by adsorption based on electrostatic interactions of negatively charged virus with a positively charged filter material.

Keywords: multi walled carbon nanotubes, water purification, virus removal, water treatment

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Authors: M. Dehestani, F. Kamali, M. Klantari Pour, L. Zeidabadi-Nejad

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Chemical bonding between polyethylene glycol (PEG) with pharmaceutical proteins called pegylation is one of the most effective methods of improving the pharmacological properties. The covalent attachment of polyethylene glycol (PEG) to proteins will increase their pharmacologic properties. For the formation of a combination of pegylated protein should first be activated PEG and connected to the protein. Interferons(IFNs) are a family of cytokines which show antiviral effects in front of the biological and are responsible for setting safety system. In this study, the nature and properties of the interaction between active positions of IFNs and polyethylene glycol have been investigated using molecular dynamics simulation. The main aspect of this theoretical work focuses on the achievement of valuable data on the reaction pathways of PEG-IFNs and the transition state energy. Our results provide a new perspective on the interactions, chemical properties and reaction pathways between IFNs and PEG.

Keywords: interaction, interferons, molecular dynamics simulation, polyethylene glycol

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Authors: Khalil Abdullah Ahmed Khalil, Elsadig Mohamed Ahmed

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Extracts of various plants material capable of decreasing blood sugar have been tested in experimental animal models, and their effects confirmed. Neem or Margose (AzadirachtaIndica) is an indigenous plant believed to have antiviral, antifungal, antidiabetic, and many other properties. In this paper deals with a comparative study of effect of aqueous Neem leaves extract alone or in combination with glibenclamide on alloxan diabetic rabbits. Administration of crude aqueous Neem extract (CANE) alone (1.5 ml/kg/day) as well as the combination of CANE (1.5 ml/kg/day) with glibenclamide (0.25 mg/kg/day) significantly decreased (P<0.05) the concentrations of serum lipids, blood glucose and lipoprotein VLDL and LDL but significantly increased (P<0.05) the concentration of HDL. The change was observed significantly greater when the treatment was given in combination of CANE and glibenclamid than with CANE alone.

Keywords: aqueos neem leaves extract, hypoglycemic, hypolipidemic, cholesterol

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Authors: I. Tulay Cagatay

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Blue-green microalgae cyanobacteria, which are important photosynthetic organisms of aquatic ecosystems, are the primary sources of many bioactive compounds such as proteins, carbohydrates, lipids, vitamins and enzymes that can be used as antimicrobial and antiviral agents. Some of these organisms are nowadays used directly in the food, cosmetic and pharmaceutical industry, or in aquaculture and biotechnological approaches like biofuel or drug therapy. Finding the effective, environmental friendly chemotropic and antimicrobial agents to control fish pathogens are crucial in a country like Turkey which has a production capacity of about 240 thousand tons of cultured fish and has 2377 production farms and which is the second biggest producer in Europe. In our study, we tested the antimicrobial activity of cyanobacterium spp. against some fish pathogens Aeromonas hydrophila and Yersinia ruckeri that are important pathogens for rainbow trout farms. Agar disk diffusion test method was used for studying antimicrobial activity on pathogens. Both tested microorganisms have shown antimicrobial activity positively as the inhibition zones were 0.45 mm and 0.40 mm respectively.

Keywords: fish pathogen, cyanobacteria, antimicrobial activity, trout

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Authors: Khalil Abdullah Ahmed Khalil, Elsadig Mohamed Ahmed

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Extracts of various plants material capable of decreasing blood sugar have been tested in experimental animal models and their effects confirmed. Neem or Margose (Azadirachta Indica) is an indigenous plant believed to have antiviral, antifungal, antidiabetic and many other properties. This paper deals with a comparative study of the effect of aqueous Neem leaves extract alone or in combination with glibenclamide on alloxan diabetic rabbits. Administration of crude aqueous Neem extract (CANE) alone (1.5 ml/kg/day), as well as the combination of CANE (1.5 ml/kg/day) with glibenclamide (0.25 mg/kg/day) significantly, decreased (P<0.05) the concentrations of serum lipids, blood glucose and lipoprotein VLDL(very low-density lipoproteins) and LDL(low-density lipoproteins) but significantly increased (P<0.05) the concentration of HDL(high-density lipoprotein). The change was observed significantly greater when the treatment was given in combination of CANE and glibenclamid than with CANE alone.

Keywords: neem, hypoglycemic, hypolipidemic, cholesterol

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Authors: Ozlem Durna Aydin, Gultekin Yildiz

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Antibiotics are microbial metabolites with low molecular weight produced by fungi and algae, inhibiting the development of other microorganisms even in low growth. Antibiotics have been used as growth factors in animal feeds for many years. They prohibited; because of increased residue problem and increased resistance to antibiotics in bacteria due to prolonged use. Aromatic plants and extracts have attracted the attention of scientists nowadays due to positive reasons such as confidence of the community to the products those are coming from nature, desire to consume, and no residue problems. Plant extracts are obtained from aromatic plants, and they come forward with antifungal, antibacterial, antiviral, antioxidant and antilipidemic properties. It has been stated that intestinal histomorphology and microbiosis are positively affected by the use of plant extract in feeds. In the present day, aromatic plants and extracts are a remarkable research field with intriguing unknowns in the field of animal nutrition, and they continue to exist in the journal in vitro and in vivo studies.

Keywords: aromatic plant, broilers, extract mechanism of action, intestinal health

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Authors: Dileep Kumar, Janhavi Ramchandra Rao Kumar, Rao

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COVID-19 has ravaged the globe, and it is spreading its Spectre day by day. In the absence of established drugs, this disease has created havoc. Some of the infected persons are symptomatic or asymptomatic. The respiratory system, cardiac system, digestive system, etc. in human beings are affected by this virus. In our present investigation, we have undertaken a study of the Indian Ayurvedic herb, Ocimum sanctum against SARS-CoV-2 using molecular docking and dynamics studies. The docking analysis was performed on the Glide module of Schrödinger suite on two different proteins from SARS-CoV-2 viz. NSP15 Endoribonuclease and spike receptor-binding domain. MM-GBSA based binding free energy calculations also suggest the most favorable binding affinities of carvacrol, β elemene, and β caryophyllene with binding energies of −61.61, 58.23, and −54.19 Kcal/mol respectively with spike receptor-binding domain and NSP15 Endoribonuclease. It rekindles our hope for the design and development of new drug candidates for the treatment of COVID19.

Keywords: molecular docking, COVID-19, ocimum sanctum, binding energy

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Authors: Shweta Sinha, Mukesh Doble, Manju S. L.

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Pyrazole scaffold is an important group of compound in heterocyclic chemistry and is found to possess numerous uses in chemistry. Pyrazole derivatives are also known to possess important biological activities including antitumor, antimicrobial, antiviral, antifungal, anticancer and anti-inflammatory. Inflammation is associated with pain, allergy and asthma. Leukotrienes are mediators of various inflammatory and allergic disorders. 5-Lipoxygenase (5-LOX) is an important enzyme involved in the biosynthesis of leukotrienes and metabolism of arachidonic acid (AA) and thus targeted for anti-inflammation. In vitro inhibitory activity of pyrazol-3-yl thiazole 4-carboxylic acid derivatives is tested against enzyme 5-LOX. Most of these compounds exhibit good inhibitory activity against this enzyme. Binding mode study of these compounds is determined by computational tool. Further experiments are being done to understand the mechanism of action of these compounds in inhibiting this enzyme. To conclude, these compounds appear to be a promising target in drug design against 5-LOX.

Keywords: inflammation, inhibition, 5-lipoxygenase, pyrazole

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Authors: Sema Şenoğlu, Sevgi Karakuş

Abstract:

Hydrazone scaffold is important to design new drug groups and is found to possess numerous uses in pharmaceutical chemistry. Besides, hydrazone derivatives are also known for biological activities such as anticancer, antimicrobial, antiviral, and antifungal. Hydrazone derivatives are promising anticancer agents because they inhibit cancer proliferation and induce apoptosis. Human carbonic anhydrase IX has a high potential to be an antiproliferative drug target, and targeting this protein is also important for obtaining potential anticancer inhibitors. The protein construct was retrieved as a PDB file from the RCSB protein database. This binding interaction of proteins and ligands was performed using Discovery Studio Visualizer. In vitro inhibitory activity of hydrazone derivatives was tested against enzyme carbonic anhydrase IX on the PyRx programme. Most of these molecules showed remarkable human carbonic anhydrase IX inhibitory activity compared to the acetazolamide. As a result, these compounds appear to be a potential target in drug design against human carbonic anhydrase IX.

Keywords: cancer, carbonic anhydrase IX enzyme, docking, hydrazone

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Authors: Huamin Xu, Wenting Jia, Hong Jiang, Junxia Xie

Abstract:

Rosmarinic acid (RA) is a natural acid that is found in a variety of herbs, such as rosemary and has multiple biological activities such as antioxidative, anti-inflammatory and antiviral activities. In this study, we investigated the neuroprotective effects of RA on dopaminergic system in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced mouse model of Parkinson’s disease (PD). The mice received oral administration of RA before MPTP injection. Results showed that the tyrosine hydroxylase expression in SN reduced and the levels of dopamine and its metabolites in the striatum decreased in MPTP intoxicated PD mice. Pretreatment with RA significantly inhibited these changes. Further studies demonstrated that MPTP treatment increased the iron content, which was counteracted by pre-treatment with RA. In addition, RA could restore the decrease of superoxide dismutase (SOD) induced by MPTP. This study provides evidence that RA could suppress MPTP-induced degeneration of the nigrostriatal dopaminergic system by regulating iron content and the expression of SOD. Thus, RA might be clinically evaluated for the prevention of neurodegenerative diseases.

Keywords: rosmarinic acid, Parkinson's disease, MPTP, dopaminergic system

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Authors: Li Yuchen, Wu Qingxin, Jin Yuxing, Yang Qian

Abstract:

Interleukin-11 (IL-11), a well-known anti-inflammatory factor, helps to protect against intestinal epithelium damage caused by physical or chemical factors. However, little is known about the role of IL-11 during viral infection. Herein, high mRNA and protein levels of IL-11 were found in epithelial cells and jejunum of piglets during porcine epidemic diarrhea virus (PEDV) infection, and IL-11 expression was positively correlated with the level of viral infection. Pretreatment with recombinant porcine IL-11 (pIL-11) suppressed PEDV replication in Vero E6 cells, while IL-11 knockdown promoted viral infection. Furthermore, pIL-11 inhibited viral infection by preventing PEDV-mediated apoptosis of cells through activating the IL-11/STAT3 signal pathway. Conversely, application of a STAT3 phosphorylation inhibitor significantly antagonized the anti-apoptosis function of pIL-11 and counteracted its inhibition of PEDV. Our data suggested that that IL-11 is a novel PEDV-inducible cytokine, and its production enhances the anti-apoptosis ability of epithelial cells against PEDV infection. The potential uses of IL-11 as a novel therapeutic against devastating viral diarrhea in piglets deserves more attention and study.

Keywords: Interleukin-11, Porcine epidemic diarrhea virus, STAT3, anti-apoptosis

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Authors: Aussara Panya, Nunghathai Sawasdee, Mutita Junking, Chatchawan Srisawat, Kiattawee Choowongkomon, Pa-Thai Yenchitsomanus

Abstract:

Dengue virus (DENV) infection is a global public health problem with approximately 100 million infected cases a year. Presently, there is no approved vaccine or effective drug available; therefore, the development of anti-DENV drug is urgently needed. The clinical reports revealing the positive association between the disease severity and viral titer has been reported previously suggesting that the anti-DENV drug therapy can possibly ameliorate the disease severity. Although several anti-DENV agents showed inhibitory activities against DENV infection, to date none of them accomplishes clinical use in the patients. The surface envelope (E) protein of DENV is critical for the viral entry step, which includes attachment and membrane fusion; thus, the blocking of envelope protein is an attractive strategy for anti-DENV drug development. To search the safe anti-DENV agent, this study aimed to search for novel peptide inhibitors to counter DENV infection through the targeting of E protein using a structure-based in silico design. Two selected strategies has been used including to identify the peptide inhibitor which interfere the membrane fusion process whereby the hydrophobic pocket on the E protein was the target, the destabilization of virion structure organization through the disruption of the interaction between the envelope and membrane proteins, respectively. The molecular docking technique has been used in the first strategy to search for the peptide inhibitors that specifically bind to the hydrophobic pocket. The second strategy, the peptide inhibitor has been designed to mimic the ectodomain portion of membrane protein to disrupt the protein-protein interaction. The designed peptides were tested for the effects on cell viability to measure the toxic to peptide to the cells and their inhibitory assay to inhibit the DENV infection in Vero cells. Furthermore, their antiviral effects on viral replication, intracellular protein level and viral production have been observed by using the qPCR, cell-based flavivirus immunodetection and immunofluorescence assay. None of tested peptides showed the significant effect on cell viability. The small peptide inhibitors achieved from molecular docking, Glu-Phe (EF), effectively inhibited DENV infection in cell culture system. Its most potential effect was observed for DENV2 with a half maximal inhibition concentration (IC50) of 96 μM, but it partially inhibited other serotypes. Treatment of EF at 200 µM on infected cells also significantly reduced the viral genome and protein to 83.47% and 84.15%, respectively, corresponding to the reduction of infected cell numbers. An additional approach was carried out by using peptide mimicking membrane (M) protein, namely MLH40. Treatment of MLH40 caused the reduction of foci formation in four individual DENV serotype (DENV1-4) with IC50 of 24-31 μM. Further characterization suggested that the MLH40 specifically blocked viral attachment to host membrane, and treatment with 100 μM could diminish 80% of viral attachment. In summary, targeting the hydrophobic pocket and M-binding site on the E protein by using the peptide inhibitors could inhibit DENV infection. The results provide proof of-concept for the development of antiviral therapeutic peptide inhibitors to counter DENV infection through the use of a structure-based design targeting conserved viral protein.

Keywords: dengue virus, dengue virus infection, drug design, peptide inhibitor

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Authors: Mahdi Asghari Ozma

Abstract:

Background and Objective:Maclurapomifera (Rafin.) Schneider, known as osage orange, is a north american native plant which has multiple applications in herbal medicine. The extract of this plant has many therapeutic effects, including antimicrobial, anti-tumor, anti-inflammation, etc., that discussed in this study. Materials and Methods: For this study, the keywords "Maclurapomifera", "osage orange, ""herbal medicine ", and "plant extract" in the databases PubMed and Google Scholar between 2002 and 2021 were searched, and 20 articles were chosen, studied and analyzed. Results: Due to the increased resistance of microbes to antibiotics, the need for antimicrobial plants is increasing. Maclurapomifera is one of the plants with antimicrobial properties that can affect all microbes, especially Gram-negative bacteria, and fungi. This plant also has anti-tumor, anti-inflammatory, anti-oxidant, anti-aging, antiviral, anti-fungal, anti-ulcerogenic, anti-diabetic, and anti-nociceptive effects, which can be used as a substance with many amazing therapeutic applications. Conclusion: These results suggest that the extract of Maclurapomifera can be used in clinical medicine as a remedial agent, which can be substituted for chemical drugs or help them in the treatment of diseases.

Keywords: maclura pomifera, osage orange, herbal medicine, plant extract

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Authors: Elif Yildiz, Gizem Gungor, Hatice Yilmaz, Duygu Gocmen

Abstract:

Nowadays, consumer demand has been increasing for the healthy and functional food. In this context, some natural products rich in phenolic compounds are also added to cereal based food for health benefits. Natural phenolic compounds have many beneficial bioactivities such as anti-allergic, antiviral, anti-inflammatory and anti-mutagenic activities. It has been found that various plant species contain natural bioactive phytochemicals with antioxidant function. One of these plant species is mahaleb (Prunus mahaleb L). Mahaleb berries with dark blue or red colours have the highest antioxidant capacities among all common fruits and vegetables. The aim of this study was to determine the possibilities of improving the antioxidant properties of novel snack crackers by supplementing with mahaleb (Prunus mahaleb L) powder. For this purpose mahaleb powder were used to replace wheat flour in the snack cracker formulation at two different levels (5%, and 7.5% w/w). As a result, mahaleb supplementation caused an increase in total phenolic contents and antioxidant activities of crackers. It can be say that mahaleb powder can be used as an alternative functional and nutritional ingredient in bakery products.

Keywords: antioxidant activity, cracker, mahaleb (Prunus mahaleb L), phenolic contents

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Authors: Hashaam Akhtar

Abstract:

IFNλR1 and IL10R2 collectively construct a heterodimer, which is an acknowledged functional receptor for all type III interferons (IFNs). Expression of IFNλR1 is highly tissue specific, which can help in making type III IFNs a drug of choice as comparable to its analogue, type I IFNs, for treating hepatitis C in the near future. Although, expression of IFNλR1 also varies with the concentration of type I IFNs, but in this study it was shown that the expression of IFNλR1 varies with the protein titers of IFN-α, IFN-λ3 and the newly discovered IFN-λ4. High dosage of IFN-α reduces the expression of IFNλR1 in HepG2 cells, which can affect the antiviral activity of type III IFNs in vivo. We premeditated an experimental strategy to differentiate monocytes into dendritic cells (DCs), type I and type II macrophages in vitro and quantified the expression of the IFNλR1 by qPCR. The exposure of newly discovered IFN-λ4 to macrophages and DCs also raised the expression of its own receptor, which shows that expression of IFN-λ4 protein in hepatitis C patient may augment type I treatment and help ease off viral titers. The results of this study may contribute in some understanding towards the mechanisms involved in the selective expression of IFNLR1 and exceptionalities associated with the receptor.

Keywords: IFNLR1, Interferon Lambda 4 (IFN-λ4), Mononuclear Phagocyte Cells (MPCs), expression

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Authors: Jackson Ishara, Ariel Buzera, Gustave N. Mushagalusa, Ahmed R. A. Hammam, Judith Munga, Paul Karanja, John Kinyuru

Abstract:

Numerous mushroom bioactive metabolites, including polysaccharides, eritadenine, lignin, chitosan, mevinolin, and astrakurkurone have been studied in life-threatening conditions and diseases such as diabetes, cardiovascular, hypertension, cancer, DNA damage, hypercholesterolemia, and obesity attempting to identify natural therapies. These bioactive metabolites have shown potential as antiviral and immune system strengthener natural agents through diverse cellular and physiological pathways modulation with no toxicity evidence, widely available, and affordable. In light of the emerging literature, this paper compiles the most recent information describing the molecular mechanisms that underlie the nutraceutical potentials of these mushroom metabolites suggesting their effectiveness if combined with existing drug therapies. The findings raise hope that these mushroom bioactive metabolites may be utilized as natural therapies considering their therapeutic potential while anticipating further research designing clinical trials and developing new drug therapies while encouraging their consumption as a natural adjuvant in preventing and controlling life-threatening conditions and diseases.

Keywords: bioactive metabolites, food functionality, health-threatening conditions, mushrooms, nutraceutical

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