استحسان کی اصلیت و ماہیت کے بارے میں مستشرقین کی آراء کا تنقیدی جائزہ

Islamic Fiqh is the representative of legal aspect of Islam. It has been originated and established on direct teachings of Qur’an and Sunnah of the Holy Prophet Muhammad (SAW). These two sources are called primary sources of Islamic law. There are some supplementary sources to the primary sources; Istihsan (Juristic Preference) is one of these. Orinetalist’s studied and produced literature on Islamic law. Istihsan has also been discussed by them but they have different opinions about its origin and its role in Islamic law. In this article their opinions are being critically analyzed and the definition, role and types of Istihsan being presented according to Muslim’s viewpoint. This research concluded that the Goldziher, Joseph Schacht, MicDonald, David Pearl, and Benjamin Jokisch explanations about the establishment of Isti╒san are not correct.

In Silico Analyses Inhibition of the Selected Pathogenic Proteins of Zika and Ebola Viruses

The catastrophe Zika virus infused in South America including Brazil and other Caribbean countries obliterated the lives and health of the inhabitants. The neonatal health was badly infected as microcephaly come out the distinctive character of this grave viral attack. The need of the hour is to dive deep in the melancholy and find out robust scientific and advanced techniques both horizontally and vertically which ward off the next generations interim of antiviral drugs and preemptive measures. Due to congenital microcephaly and Guillain-Barre syndrome in human, Zika virus has been gaining attention from scientists. The Zika virus is amongst Flaviviruses like Dengue virus, Japanese encephalitis, Yellow Fever virus, Thick Warm virus and West Nile virus. These are mosquitoes borne human pathogens specially species Aedes aegypti. There are numerous proteins responsible for the pathogenesis of virus including seven of the NS proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) which are integral part of replication complex, located at the cytoplasmic side of the endoplasmic reticulum membrane. Among these proteins three were selected as drug targets to halt virus infections. Availability of the X- ray crystal structures of Zika virus proteins enabled structure based drug design efforts. First drug target was lipid containing glycosylated NS1 that makes a homodimer inside the cells while its secretion take place inside the extracellular space as hexameric lipoprotein. This leads to the evasion of immune system and causes pathogenesis through establishment of interaction with components from both innate and adaptive immune system as well as other host factors. The second drug target was NS3 helicase protein triggered pathogenesis through replication of RNA and it depends upon ATP. NS3 is one of the most thoroughly studied antiviral drug targets. The enzymatic activity is coupled with the C-terminal region of the nonstructural protein NS3 in Flaviviruses, namely an RNA helicase (NS3-Hel) concerned in genome replication and RNA synthesis. The third target was NS5 protein which is distinctive among other RNA viruses because it contains a fused domain composed of two terminals an Nterminal RNA methyltransferase (MTase) domain and a C-terminal RNA-dependent RNA polymerase (RdRp) domain. The N-terminal MTase domain is responsible for 5′capping and thereby stabilizes the viral RNA genome, while the C-terminal RdRp domain is critical for viral RNA replication and beleaguered for inhibition. The above mentioned non-structural proteins were selected for molecular docking study while following various classes of compounds comprising flavonoids, 1,4-benzothiazene analogues and non-nucleoside inhibitors were selected for molecular docking. The docking results obtained would be exploration in the development of novel potent inhibitors because of the predicted adequate theoretical binding affinities. The molecular docking results were further corroborated with molecular dynamics simulation study including RMSD, RMSF, Rg, HB, P.E, MM/PBSA and PCA results which abetted in the finding of binding modes of inhibitor into the pocket and consequently used to incorporate flexibility in both components of complex which sturdily confirmed and supported the docking study. Besides, Zika virus another deadly virus is Ebola virus (EBOV) and it is a filamentous, enveloped, non-segmented, negative–strand ribonucleic acid (RNA) virus which belongs to family Filoviridae. Ebola virus includes different glycoproteins each of which plays their roles in different aspects of viral life cycle. The secreted glycoprotein (sGP) is a nonstructural protein with a single frame and has total 364–372 residues. Towards the N-terminal 295 residues which also include the signal sequence are similar with full length GP. It differs in the length of C-terminal sequences. The secreted glycoprotein is essential for virology therefore, it can be a decent drug target for the development of novel inhibitors. The lack 3D crystal structure of secreted glycoprotein is big hurdle in designing of drugs against Ebola virus. Therefore, In silico techniques were used to build model including homology modeling and built model was refined through simulation. Furthermore, docking was done through known classes of antiviral drugs and results were found satisfactory.