On January 2020, a new coronavirus (officially named SARS-CoV-2) was associated with alarming outbreak of a pneumonia-like illness, which was later named by the WHO as COVID-19, originating from Wuhan City, China. Although many clinical studies involving antiviral and immunomodulatory drug treatments for SARS-CoV-2 all without reported results, no approved drugs have been found to effectively inhibit the virus so far. Full genome sequencing of the virus was done, and uploaded to be freely available for the world scientists to explore. A promising target for SARS-CoV-2 drug design is a chymotrypsin-like cysteine protease (3CLpro), a main protease responsible for the replication and maturation of functional proteins in the life cycle of the SARS coronavirus. Here we aim to explore SARS-CoV-2 3CLpro as possible drug targets based on ligand- protein interactions. In addition, ADME properties of the ligands were also analyzed to predict their drug likeliness. The results revealed Out of 9 ligands, 8 ligands (JFM, X77, RZG, HWH, T8A, 0EN, PEPTIDE and DMS) showed best ADME properties. These findings suggest that these ligands can be used as potential molecules for developing potent inhibitors against SARS-CoV-2 3CLpro, which could be helpful in inhibiting the propagation of the COVID-19. Furthermore, 10 potential amino acids residues were recognized as potential drug binding site (THR25, HIS41, GLY143, SER144, CYS145, MET165, GLU166, GLN189, ASP295 and ARG298). All those amino acid residues were subjected to missense SNP analysis were recognized to affect the structure and function of the protein. These characteristics provide them the promising to be target sites for the fresh generation inhibitors to work with and overcome drug resistance. These findings would be beneficial for the drug development for inhibiting SARS-CoV-2 3CLpro hence assisting the pharmacogenomics effort to manage the infection. of SARS-CoV-2.

Introduction:The proto-oncogene (MPL) gen encodes the receptor for thrombopoietin (TPO-R), a member of hematopoietic receptor superfamily. Thrombopoietin (TPO), the primary cytokine regulating self-renewal of hematopoietic stem cells, thrombopoiesis and megakaryocytopoiesis. TPO binding to TPO-R induces activation of Janus Kinase 2 (JAK2). Activated JAK2 triggers the activation of downstream positive signaling pathways, leading to the survival, proliferation, and differentiation of hematopoietic cells. Mutations in MPL gene possibly will alter the normal regulatory mechanisms. Numerous MPL mutations have been observed in various hematopoietic cancers such as essential thrombocythemia and primary myelofibrosis and leukemias. In this study, we performed a comprehensive in silico analysis of the functional and structural impact of non-synonymous (nsSNP) that are deleterious to TPO-R structure and function. Methodology: The data on human MPL gene was retrieved from dbSNP/NCBI. Nine prediction algorithms; SIFT, Polyphen, PROVEAN, SNAP2, Condel, PhD-SNP, I-Mutant, Mutpred. RaptorX and Chimera were used to analyzing the effect of nsSNPs on functions and structure of the TPO-R. STRING and KEGG database were used for TPO-R protein-protein interaction. Results and Discussion:As per dbSNP database, the human MPL gene contained 445 missense mutations. A total 5 nsSNPs (D295G, R257C, Y252H, R537W and D128Y) were predicted to have the most damaging effects on TPO-R structure and function. STRING and KEGG revealed that MPL had strong interactions with proteins that involved in cell growth, apoptosis, signal transduction pathway, some cancers pathways such as colorectal cancer, lung cancer, pancreas cancers, and skin cancer. A literature search revealed that Y252H has contribute to the development of essential thrombocythemia.Conclusion: These in silico predictions will provide useful information in selecting the target SNPs that are likely to have functional impact on the TPO-R and moreover could act as potential targets in genetic association studies.

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Introduction:The PIK3R1 (phosphoinositide-3-kinase regulatory subunit 1) and PlGF (Placenta growth factor)genes share some common pathways with eNOS,( Endothelial nitric oxide synthase) that plays a vital role in angiogenesis of blood vessels and regulating endothelial function. The PIK3R1 gene encodes the receptor for the p85α regulatory subunit of the phosphoinositide-3-kinase (PI3K), that involved in endothelial cell migration. The PlGF gene encodes for the placenta growth factor, a homolog of vascular endothelial growth factor (VEGFA) that is involved in angiogenesis. PIK3R1 and/or PlGF mutations may cause dysregulation of eNOS contributing to endothelial dysfunction in preeclampsia. This study aims to analyze the effect of mutation of the PIK3R1 and PlGF genes on the structure and function of PIK3R1 and PGF protein that may have an important role in pathogeneses of preeclampsia. Methodology: The data on human PIK3R1and PGF genes were retrieved from dbSNP/NCBI. Ten prediction algorithms; SIFT, PROVEAN, Polyphen, SNAP2, SNPs&GO, PANTHER PhD-SNP, I-Mutant, Mutpred, and Hope were used to analyzing the effect of nsSNPs on functions and structure of the PGF and PIK3R1 protein. STRING and KEGG databases were used for PGF and PIK3R1 protein-protein interaction. Results and Discussion: As per the dbSNP database, the humanPIK3R1gene contained 365 missense mutations. A total 3nsSNPs (T239M, S229W, E47K) and 2 nsSNPs (H125Y, V59G) were predicted to have the most damaging effects on the structure and function of PIK3R1 and PGF respectively. STRING and KEGG revealed that PIK3R1and PGF had strong interactions with proteins involved in the VEGF signaling pathway and PI3K-Akt signaling pathway. PIK3R1 is confirmed to be linked to important diseases like preeclampsia and can affect its treatment response. Conclusion: Genegene interaction is an important factor in preeclampsia treatment, the effect of mutation of the PIK3R1 and PlGF genes on the structure and function of PIK3R1 and PGF protein may have an important role in pathogeneses of preeclampsia. Also, these are linked to its treatment effect. This document gives formatting instructions for authors preparing papers for publication in the journal. Authors are encouraged to prepare manuscripts directly using this template. This template demonstrates the format requirements for the Journal.

Background: Peptic ulcer disease has a high burden worldwide and the commonest causative agent is H. pylori which are usually eradicated with omeprazole-based triple therapy. Pharmacogenetics is an important branch of pharmacology and should be applied to assist the clinical usage of medicines which has a strong relation with enzyme activity of certain genes and alleles known through the literature. CYP2C19 is known to affect the activity of omeprazole and this will result in different responses to treatment. The commonest alleles through the literature are CYP2C19*2, and CYP2C19*3 which vary according to different ethnicity of different populations. Aim: In Sudan, there are versatile ethnic groups which might affect the response to treatment by many drugs dependent genotypes for example CYP2C19 and Omeprazole interaction and hence studies in this area should be done as they are few. Methodology: A purposeful convenient sampling; in which patients with peptic ulcer disease and treated with omeprazole were reviewed and the PCR is used to differentiate the CYP2C19 different alleles in patients presenting from February 2016 to January 2017. Results: In the present study we investigated the distribution of three common gene variants affecting the omeprazole treatment of peptic ulcer disease and H. pylori eradication namely to CYP2C19*2, *3 and *7. The CYP2C19*2 mutation was found among all seven ethnic groups of Sudan, Arabs mostly 17 (139) followed by Darforians 9 (139), Beja 6 (139) and Nilotics 6 (139), Nuba 5 (139) then, Nubians 3 (139) and Fulani 1 (139), p=0.048 which is significant. Regarding CYP2C19*3 mutation of this allele is found in certain ethnic groups Arabs 6 (139), Nubians 6 (139) and Nuba 2 (139), p=0.043 significant. There is no mutation found among different Sudanese ethnic groups in CYP2C19*7. Arabs are normal homozygotes 6 (139) and Darforians 1 (139). Nuba 1 (139) were found to be heterozygotes in this allele p=0.038 significant. Treatment of H. pylori with omeprazole-based triple therapy was used in 110 (139) and no significant correlation found with the different ethnic groups of Sudan. Conclusion: These data indicate that Sudanese seven ethnic groups showed activity of CYP2C19*2, CYP2C19*3 were they took omeprazole based triple treatment and some of them showed activity to CYP2C19*7.