15. Al-Hijr/The Rocky Tract
I/We begin by the Blessed Name of Allah
The Immensely Merciful to all, The Infinitely Compassionate to everyone.
15:01
Alif. Lam. Ra’.
These are Messages of the Divine Book - that is a Clear Qur’an.
15:02
a. The time will come when those who disbelieve now will wish that they were Muslims.
15:03
But leave them alone to feast and enjoy themselves as if it is the only aim of life, and let their wishful hopes distract them.
For they will soon realize the futility of their endeavors.
15:04
a. And WE have never destroyed any settlement or a community for its wrongdoing without its having a known decree beforehand.
15:05
a. No community can either precede its appointed time of doom nor delay it.
15:06
And they say:
‘O you - Muhammad - upon whom this Reminder - the Qur’an – is being sent down as you claim!
We think you are certainly possessed’ and insane.
15:07
a. So ‘why are you not bringing us the angels to testify your truthfulness, if you are of the truthful?’
15:08
However, WE do not send down the angels except with demands of the truth,
and were the angels to appear now with the decision, then they will not be spared.
15:09
Indeed, it is WE WHO are sending down this Reminder – The Qur’an, and
surely, WE will preserve it against any satanic change in its Sacred Arabic Text and its form.
15:10
a. And, certainly, WE did assign the Messengers before you among the earlier communities,
Muḥmood Sami al Barodi is a famous poet who was named the Resurrector of poetry in the early times when many poets of the old era were the cause of the decline in poetry. His poems had been studied from many aspects and by many scholars but no one ever spoke about al Barodi’s writings about wisdom. This article is focusing on the verses and poems that focus on the meaning of wisdom and everything that relate to it. He talked about the importance of wisdom in the poems as he encouraged the other poets to give attention to this meaning. Some published books and articles helped me write this article but I haven’t found any of them that gave this point enough significance though his poetry is full of verses about wisdom and so I chose to write about it.
Pakistan is reporting high number of polio cases during the last few years and the disease is continuously spreading. Poliovirus 2A protease (2Apro) is multifunctional proteinase performing vital roles during viral replication and cellular damage. RNA from polio infected blood samples and also from live attenuated polio vaccine was extracted followed by 2Apro amplification cloning and sequencing. The sequences were compared against the standard consensus 2Apro sequence obtained from Genbank to analyse mutations. In order to understand more concerning PV2Apro the protein was over-expressed in bacteria following amplification using sense and antisense primers and cloning in pET15b. Several expression hosts were tested and BL21 (DE3) pLysS cells gave the best expression of PV2Apro with minimal unwanted protein expression following IPTG induction. The 2Apro protein was purified to homogeneity using column chromatography, its solubility determined and its molecular weight and composition determined by MALDI-TOF mass spectrometry. The purified protein had a slightly lower molecular weight than predicted. Several attempts were made to concentrate the protein using different buffers for ion exchange and crystallization procedures. However after every buffer change to reduce imidazole concentration, protein was gradually degraded. The 3D structure of 2Apro was determined and optimized by homology modelling followed by an energy minimization protocol. Structural validation programs VADAR and QMEAN were used to verify the 2Apro model. Analysis of protein stability changes of poliovirus 2A protease-mutated sequences using various servers was also performed. Furthermore, mutation pattern, intrinsic disorder regions (IDRs), hydrophobic regions, drug binding sites (DBS) and subcellular localization were identified. Hydrophobicity results confirmed the suitability and reliability of 2A protease as a potential drug target. Less IDRs were observed in the protein. In order to predict the molecular basis of interaction of small molecular agonists, docking simulation was performed on a structurally diverse dataset of known inhibitors of PV2Apro. Docking results were employed for missense mutations to predict extremely damaging to the protein structure as well as the function of the protease. Intrinsic disorder regions (IDRs), drug binding sites (DBS), and protein stability changes upon mutations were also identified among them. Our results demonstrated dominant roles for Gly 1, Lys 15, His 20, Cys 55, Cys 57, Cys 64, Cys 109, Gly 110 and Gly 111 within the binding pocket of PV2Apro. Upon subjecting these sites to single nucleotide polymorphism (SNP) analysis, we observed that out of 155 high risk SNPs, 139 residues decrease the protein stability. We conclude that these missense mutations can affect the functionality of the 2A protease, and that identified protein binding sites can be directed for the attachment and inhibition of the target proteins. Mutations detected in this study were also found to be interacting with the inhibitors proving them to be valuable tool for in formulating new drugs to inhibit polio virus replication. We have identified residues which would be helpful in the development of future selective drugs along with as important inhibitors to inhibit the replication of poliovirus.