An in silico investigation of phytochemicals as potential inhibitors against non-structural protein 1 from dengue virus 4

Dengue fever has emerged as a big threat to human health since the last decade owing to high morbidity with considerable mortalities. The proposed study aims at the in silico investigation of the inhibitory action against DENV4-NS1 of phytochemicals from two local medicinal plants of Pakistan. Non-Structural Protein 1 of Dengue Virus 4 (DENV4-NS1) is known to be involved in the replication and maturation of viron in the host cells. A total of 129 phytochemicals (50 from Tanacetum parthenium and 79 from Silybum marianum) were selected for this study. The tertiary structure of DENV4-NS1 was predicted based on homology modelling using Modeller 9.18 and the structural stability was evaluated using molecular dynamics simulations. Absorption, distribution, metabolism, excretion and toxicity (ADMET) along with the drug-likeness was also predicted for these phytochemicals using SwissADME and PreADMET servers. The results of ADMET and drug-likeness predictions exhibited that 54 phytochemicals i.e. 25 from Tanacetum parthenium and 29 from Silybum marianum showed effective druglikeness. These phytochemicals were docked against DENV4-NS1 using AutoDock Vina and 18 most suitable phytochemicals with binding affinities ≤ -6.0 kcal/mol were selected as potential inhibitors for DENV4-NS1. Proposed study also exploits the novel inhibitory action of Jaceidin, Centaureidin, Artecanin, Secotanaparthenolide, Artematin, Schizolaenone B, Isopomiferin, 6, 8-Diprenyleriodictyol, and Anthraxin against dengue virus. It is concluded that the screened 18 phytochemicals have strong inhibition potential against Dengue Virus 4

Sharia Screening Process: A Comparison of Pakistan and Malaysia

This paper aims to examine the Sharia screening methodologies used by Securities Commission of Malaysia and KSE Meezan Index (KMI-30 of Pakistan). The two set of screens used by both Islamic indices are business screens and financial screens. The existence of certain similarities and differences in screening methodology is evident. The findings also implicate that there is a dire need for standardisation of said process which will be beneficial in many ways and will surely aid in the development of ICM worldwide.

Energy management in harvesting enabled sensing nodes: prediction and control

Energy efficient transmission rate regulation of wireless sensing nodes, is a critical issue when operating in an energy harvesting (EH) enabled environment. In this work, we view the energy management problem as a queue control problem where the objective is to regulate transmission such that the energy level converges to a reference value. We employ a validated non-linear queuing model to derive two non-linear robust throughput controllers. A notable feature of the proposed scheme is its capability of predicting harvest-able energy. The predictions are generated using the proposed Accurate Solar Irradiance prediction Model (ASIM) whose effectiveness in generating accurate both long and short term predictions is demonstrated using real world data. The stability of the proposed controllers is established analytically and the effectiveness of the proposed strategies is demonstrated using simulations conducted on the Network Simulator (NS-3). The proposed policy is successful in guiding the energy level to the reference value, and outperforms the Throughput Optimal (TO) policy in terms of the throughput achieved

in silico discovery of potential inhibitors against Dipeptidyl Peptidase-4: A major biological target of Type-2 diabetes mellitus

Objectives: Type-2 diabetes mellitus, caused by impaired secretion of insulin, is becoming one of the health hazardous threats to human lives across the world. Its prevalence is rising with time. In this study, 2750 phytochemicals, that are considered to have great ability to eliminate diseases caused by different viruses and bacteria, are obtained from different medicinal plants and discovery of inhibitors through in silico method was performed against Dipeptidyl peptidase-4 (DPP4). Method: The pharmacological assessment and pharmacokinetics of phytochemicals, molecular docking and density functional theory (DFT) analysis helped to explore the inhibitory action of phytochemicals against DPP4. Total forty-nine phytochemicals were screened initially to reduce the number of compounds to be analyzed further based on a threshold of binding affinity ≥ -5.5 kcal/mol and were considered for further computational studies to analyze their inhibitory effects for DPP4. For comparison and validation of the results of present study, various previously reported and experimentally validated compounds were docked with the DPP4. For these dockings, binding affinity was predicted and compared with those of phytochemicals to check if these phytochemicals are competent enough to be used as an inhibitor in the treatment of diabetes mellitus in the future. Results: Only four phytochemicals showed binding affinity greater than those of experimentally validated compounds. These included two phytochemicals from Silybum marianum, i.e. Diprenyleriodictyol and Taxifolin and while other two phytochemicals from Santolina insularis and Erythrina Varigatae i.e. Papraline and Osajin respectively. The reactivity levels for these four phytochemicals with the binding site residues of DPP4 were obtained by DFT based analysis, in which ELUMO, EHOMO and band energy gap were computed. Conclusion: Based on these results, it is concluded that these four phytochemicals, after passing through in vitro and in vivo validation, can be utilized as potential DPP4 inhibitors as they have strong properties as compared to those of various experimentally validated inhibitors

Probing the Pharmacological Parameters, Molecular Docking and Quantum Computations of Plant Derived Compounds Exhibiting Strong Inhibitory Potential Against NS5 from Zika Virus

ABSTRACT Zika virus (ZIKV) is known for microcephaly and neurological disease in humans and the nonstructural proteins of ZIKV play a fundamental role in the viral replication. Among the seven nonstructural proteins, NS5 is the most conserved and largest protein. Two major functional domains of NS5 i.e. methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) are imperative for the virus life cycle and survival. The present study explicates the inhibitory action of phytochemicals from medicinal plants against NS5 from ZIKV, leading to the identification of potential inhibitors. The crystal structure of the protein is retrieved from RCSB protein data bank. A total of 2035 phytochemicals from 505 various medicinal plants are analysed for their pharmacological properties and pharmacokinetics. Compounds having effective drug-likeness are docked against the protein and further analysed using density functional theory approach. Among the 2035 phytochemicals, 13 are selected as potential inhibitors against MTase having high binding affinities and 17 compounds are selected for RdRp. HOMO and LUMO energies are calculated for the docked compounds within and outside binding pockets of MTase and RdRp, adapting the B3LYP hybrid exchange-correlation functional with def2-SV(P) basis set. Physicochemical properties such as ionization energy, electronic chemical potential, electronegativity, electron affinity, molecular softness, molecular hardness and electrophilicity index have also been analysed for selected phytochemicals. Based upon the results, it is concluded that the selected phytochemicals are highly competent to impede the replication of the virus by inhibiting the ZIKV-NS5

Computer-aided Analysis of Selective Phytochemicals as Potent Inhibitors of Parkin: Major Biological Target of Parkinson’s disease

Parkinson’s disease, caused by mutations in the Parkin that leads to loss of neuron is the second most widespread neurodegenerative disorder in the world. Phytochemicals are being considered due to their medicinal properties to cure many human diseases. The present study targets the inhibition of Parkin, a major biological target for Parkinson using 3150 phytochemicals from various medicinal plants. These plants are naturally growing in a local climate of Pakistan, India and China and being used for a long time for the medicinal purpose. A total of 3150 phytochemicals from various medicinal plants were collected for this in silico study. The pharmacological assessments prediction, molecular docking and density functional theory (DFT) based studies were done to find out the latent inhibitory properties of these phytochemicals against Parkin. Out of 3150 phytochemicals, 175 showed human-suitable pharmacological properties and among those 175 compounds, 5 phytochemicals, i.e. Liquirtin, Shinflavanone, Glabrone, GlycyrdioneB and IsoangustoneA to have potent inhibitory properties against Parkin and can be deliberated for additional in vitro and in vivo studies to evaluate their inhibitory effects against Parkin. They revealed binding affinity greater than various previously reported inhibitors against Parkin. Additionally, DFT based analysis exhibited high reactivity for these five phytochemicals in the binding pocket of Parkin, based on ELUMO, EHOMO and band energy gap. A total of 5 out of 175 phytochemicals are reported as highly potent inhibitors against Parkin which are liquirtin, Shinflavanone, Glabrone, Glycyrdione B and IsoangustoneA from the same medicinal plant Glycyrrhiza glabra. However, these 5 phytochemicals can be considered for further in vivo and in vitro analysis for the clinical development of a drug against the world’s second most common brain disorder, the Parkinson’s disease.</p

Virtual Screening of Phytochemicals by Targeting HR1 Domain of SARS-CoV-2 S Protein: Molecular Docking, Molecular Dynamics Simulations, and DFT Studies

The recent COVID-19 pandemic has impacted nearly the whole world due to its high morbidity and mortality rate. Thus, scientists around the globe are working to find potent drugs and designing an effective vaccine against COVID-19. Phytochemicals from medicinal plants are known to have a long history for the treatment of various pathogens and infections; thus, keeping this in mind, this study was performed to explore the potential of different phytochemicals as candidate inhibitors of the HR1 domain in SARS-CoV-2 spike protein by using computer-aided drug discovery methods. Initially, the pharmacological assessment was performed to study the drug-likeness properties of the phytochemicals for their safe human administration. Suitable compounds were subjected to molecular docking to screen strongly binding phytochemicals with HR1 while the stability of ligand binding was analyzed using molecular dynamics simulations. Quantum computation-based density functional theory (DFT) analysis was constituted to analyze the reactivity of these compounds with the receptor. Through analysis, 108 phytochemicals passed the pharmacological assessment and upon docking of these 108 phytochemicals, 36 were screened passing a threshold of -8.5 kcal/mol. After analyzing stability and reactivity, 5 phytochemicals, i.e., SilybinC, Isopomiferin, Lycopene, SilydianinB, and Silydianin are identified as novel and potent candidates for the inhibition of HR1 domain in SARS-CoV-2 spike protein. Based on these results, it is concluded that these compounds can play an important role in the design and development of a drug against COVID-19, after an exhaustive in vitro and in vivo examination of these compounds, in future

Tit comparative effects of mulligan traction straight leg raise versus muscle energy technique on pain intensity and hamstring tightness in patient with knee osteoarthritis

Objective: To determine the comparative effects of mulligan traction straight leg raise versus muscle energy technique on pain intensity and hamstring tightness in patient with knee osteoarthritis. Methodology: The design of this study was randomized clinical trial.&nbsp; Data was collected from Physiotherapy Clinics, the University of Faisalabad. The sample size was of 36 subjects. Informed consent was signed by all participants. Participants were included in study by considering inclusion and exclusion criteria. Subjects were divided randomly by lottery method into two groups, group A (mulligan traction straight legs raise technique) and group B (Muscle energy technique). Total treatment was of 4 weeks.&nbsp; Outcomes measures tool were, VAS (visual analogue scale) for pain intensity and Oxford knee score (OKS) for disability. Active Knee Extension test was used to assess hamstring flexibility. Results: Mean Age of the group A participants were 53.89±5.76 and group B age 56.39±5.78. MET group was more effective in improving knee function rather that mulligan group (42.6±4.3 vs 34.3±5.1 with p value .000) similarly. MET group was more effective in improving hamstring flexibility and in pain reduction her that mulligan group (17.1±3.6 vs 24.6±4.7 with p value .000; 1.4±.5 vs3.4±.8 with p value .000)