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.

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.

Knowledge, attitude and practices about needle stick injuries in healthcare workers

To assess knowledge, attitude and practices about needle stick Injuries in health care workers. Hospital based study carried out at Pakistan Institute of Medical Sciences, Islamabad, from August 2010 to November 2010. A self administered 19 items questionnaire was prepared which contained information about needle stick injuries, its awareness, frequency of injury and the protocols that were followed after an injury had occurred. These questionnaires were given to 500 health care workers working in different wards and theaters of the hospital after obtaining their informed written consent. The health care workers included doctors, nurses and paramedical staff of Pakistan Institute of Medical Sciences, Islamabad. The data was entered and analyzed using SPSS version 15. A total of 500 health care workers filled the questionnaire and returned it. Out of these 416[83.2%] reported ever experiencing needle stick injuries in their professional life. Health care workers working in Emergency department were most frequently affected [65%] followed by those working in different wards [27%] and operation theatre [8%]. Most [93.6%] workers had knowledge about needle stick injuries and only 6.4% were not aware of it. Needle stick injury occurred from a brand new [unused] syringe in 51.2% cases, while in 32.8% cases, the needle caused an injury after it had been used for an injection. In 5% cases, injury occurred with blood stained needles. The commonest reasons for needle injury in stick injuries were heavy work load [36.8%] followed by hasty work [33.6%] and needle recapping [18.6%]. About 66% health care workers were already vaccinated against hepatitis B. Only 13% workers followed universal guidelines of needle stick injuries and no case was reported to hospital authorities. Health care workers had inadequate knowledge about the risk associated with needle stick injuries and do not follow standard preventive measures. A standard protocol regarding the training and compliance to follow preventive measures should be followed in all health care institutions