البعد الأخلاقي في سياسة الرسول صلى الله عليه وسلم

The Arab’s tribes were diverse and were scattered all over Arabia. They were alien to any system, were unfamiliar of any rules and regulations. When the prophet PBUH came to them, He gently handled them, made them lenient, gathered them at the one true platform and eventually he was succeeded in uplifting them into the bondage of brotherhood. He guided them towards the political structure so that they can live under its shadow and follow its rules and regulations. He trained amongst them Preachers, judges, leaders and politicians. He sent his messengers to all the rulers of the worlds. These messengers were able to shake the Persians and Roman thrones which were considered the greatest empires of that time. They all got united against this newly arising force which later brought the greatest revolution in the history of humankind. The solutions presented by the Prophet PBUH while confronting the challenges in spreading his message,  enjoy the political wit, which is considered far better than the wit of political scholars and political tycoons. His ability of prior reading of the incidents, uncovers his huge potential in his prior dealing of the matters and suggesting its solutions and substitutes. His policies played a vital role in establishing the prior relations with Njashi, and later to facilitate the Muslims during their first immigration towards Abyssinia from the cruelty of the idolaters. Moreover, He chose the best time for the Treaty of Hudaybiyyah and Conquest of Mecca. He chose among his companions the one who knew the International languages and sent them as his Ambassadors to the rulers and tribal chiefs along with his written or verbal messages. He addressed the each with the method appropriate to him and suited him the best. He made best use of alliance, as he alienated the Arab tribes, from Jews and the others. In this way he was able to take a huge time to concentrate on those nations and was able to make a lot of allies. In his internal policy matters, he always tried to solve his problems, developing the society and to sabotage the malicious intentions which were planned by hypocrites, who were considered as his most dangerous enemies. His policy towards them was to admit apparently and leaving their unrevealed intentions to ALLAH. He treated them well, because he was anxious on preserving the freedom of all and the unity among his companions. When their malicious intentions started turning to become a threat to the security of Islam and started harming the interests of the society, He had not reply them strongly and dissuasively. He demolished the Mosque through which they were planning to harm the Muslim community. Moreover, he drew a line to their plans of aggression without harming anyone. He was very witty in his policies through which he was able to defeat them in the end. In this way he was able to change the course of the whole history on mankind. In this research we will try to deal with his moral wit which is considered the main characteristic of his policy.

In Vitro Characterization of Hepatitis C Virus Rna Dependent Rna Polymerase

Hepatitis C virus (HCV) is a major health problem throughout the world with high morbidity and mortality. HCV has high mutation rate and is classified into six genotypes (GT). The major prevalent genotype in Pakistan is 3a. While inhibitors of the HCV protease are now available to treat patients infected with GT1 HCV, treatment options are limited for other HCV genotypes. The aim of the study was to analyze the effect of different inhibitors / HCV structural genes (Core, E1, E2 & P7) on the activity of HCV polymerase in 5BR assay and to develop a global consensus sequence of HCV NS5B. The 5BR assay was used to screen non-nucleoside inhibitors (NNI) against the GT3a HCV RdRp and determine the EC50 of HCV-796. Binding of hits to recombinant GT3a RdRp was determined using a differential fluorimetry assay. RNA synthesis by the recombinant protein was used to determine the IC50 of HCV-796. A mutation in the 3a RdRp that conferred resistance to inhibition by HCV-796 was identified using the 5BR assay and by RNA synthesis in vitro. Pan genotypic effect of HCV-796 was analyzed by using HCV polymerase from all the six HCV genotypes in 5BR assay. Effect of HCV structural genes on the activity of HCV polymerase was analyzed by using wild type polymerase, ∆21 polymerase and GAA mutant polymerase in 5BR assay. To develop a global consensus sequence of HCV NS5B; 236 HCV NS5B sequences belonging from all over the world were aligned and a representing phylogenetic tree was drawn. xix Inhibitors screening showed that HCV-796 decreased the activity of GT3a RdRp with an EC50 of 90 nM in the 5BR assay. In biochemical assays, HCV-796 had an IC50 of 88 nM for de novo initiation and 229 nM for primer extension. In the differential scanning fluorimetry assay, binding to HCV-796 significantly altered the denaturation profile of the 3a RdRp. A C316Y mutant that conferred resistance to HCV-796 in GT1 RdRp was found to render the 3a RdRp resistant to HCV-796 by more than one log in both the 5BR and the biochemical assays. When the effect of HCV structural genes was analyzed on the activity of HCV polymerase in cell bases assay, HCV core gene showed maximum increase of 10 fold by using wild type polymerase. Consensus sequence analysis showed that the active site residues D220, D225, D318 and D319, which bind the divalent cations, are highly conserved among all the HCV genotypes. The HCV NS5B phylogenetic tree showed the clusters of different genotypes and their evolutionary relationship. Given the high mutation rate of HCV, the residues which are present in the catalytic pocket, sugar selection and template/primer interaction are highly conserved, although we observed, at many places where change in nucleotide sequences did not affect the amino acid sequences of HCV NS5B. The NNI HCV-796, a known inhibitor for GT1 HCV RdRp, could also inhibit the 3a polymerase. HCV-796 should serve as a useful scaffold for further development of effective non-nucleoside inhibitor for GT3a HCV. HCV core gene increased the activity of HCV polymerase in cell based assay. The phylogenetic analysis suggested that different HCV genotypes evolved from genotype 1a.