A b s t r a c t Introduction: The SARS-CoV-2 (previously 2019-nCoV) outbreak in Wuhan, China and other parts of the world affects people and spreads coronavirus disease 2019 (COVID-19) through human-to-human contact, with a mortality rate of > 2%. There are no approved drugs or vaccines yet available against SARS-CoV-2. Material and methods: State-of-the-art tools based on in-silico methods are a cost-effective initial approach for identifying appropriate ligands against SARS-CoV-2. The present study developed the 3D structure of the envelope and nucleocapsid phosphoprotein of SARS-CoV-2, and molecular docking analysis was done against various ligands. Results: The highest log octanol/water partition coefficient, high number of hydrogen bond donors and acceptors, lowest non-bonded interaction energy between the receptor and the ligand, and high binding affinity were considered for the best ligand for the envelope (mycophenolic acid: log P = 3.00; ΔG = -10.2567 kcal/mol; pKi = 7.713 μM) and nucleocapsid phosphoprotein (1-[(2,4-dichlorophenyl)methyl]pyrazole-3,5-dicarboxylic acid: log P = 2.901; ΔG = -12.2112 kcal/mol; pKi = 7.885 μM) of SARS-CoV-2. Conclusions: The study identifies the most potent compounds against the SARS-CoV-2 envelope and nucleocapsid phosphoprotein through state-ofthe-art tools based on an in-silico approach. A combination of these two ligands could be the best option to consider for further detailed studies to develop a drug for treating patients infected with SARS-CoV-2, COVID-19.
Introduction:The current study aimed to describe genotypes associated with Hodgkin lymphoma (HL) in a cohort of Saudi and non-Saudi patients and discuss their possible susceptibility to HL. Methods:We studied clinical, histopathological, and laboratory findings of HL patients admitted over 12 years duration, at King Fahd University Hospital, KSA. The genomic DNAs of HL patients (n = 61) and normal control subjects (n = 36) were extracted, and genotyping was performed using the Illumina human exome bead chip.Set of HL patients and set of normal controls were included in this study.Results: A total of 35 DNA variants were found to be highly significant with the P-value <9.90 × 10 −11 among 243 345 exonic biomarkers and obeying the Hardy-Weinberg equilibrium. Nine, MEGF11-rs150945752 (P-value 1.20 × 10 −12 ), CACNA1I-s58055559 (P-value 1.93 × 10 −12 ), DECR2-rs146760080 (P-value 2.19 × 10 −12 ), STAB1-rs143894786 (P-value 2.45 × 10 −12 ), ZNF526-rs144433879 (P-value 2.76 × 10 −12 ), CPLANE1-rs200612080 (P-value 3.77 × 10 −12 ), DLK1-rs1058009 (P-value 5.95 × 10 −12 ), RTN4RL2-rs61745214 (P-value 7.71 × 10 −12 ), and PGRMC1-rs145582672 (P-value 8.56 × 10 −12 ), exonic variants on chromosomes 15, 22, and 16 were highly associated with HL cases.The highly significant haplotypes at chromosome 3: rs143894786G; rs149982219G with P-value = 3.43 × 10 −14 was found to be the risk haplotype for the HL patients.The opposite alleles at chromosome 3: rs143894786A; rs149982219G is protective with P-value = 2.46 × 10 −12 . Maximum number of SNPs at the chromosome 19: rs144433879C; rs181265966G; rs201144421C; rs145591797G; rs200560875G; rs77270337G (risk P-value = 2.24 × 10 −12 ) and its opposite allele rs144433879A; rs181265966A; rs201144421T; rs145591797A; rs200560875A; rs77270337A (protective P-value = 2.60 × 10 −9 ) were found to be associated haplotype with the HL and controls, respectively, in Saudi population. Conclusion:Our study concludes that the HL is genetically heterogeneous with multigene causation.
Family trio next-generation sequencing-based variant analysis was done to identify the genomic reason on unexplained recurrent pregnancy loss (RPL). A family (dead fetus and parents) from Saudi Arabia with an earlier history of three unexplained RPLs at the ninth week of pregnancy was included in the study. Whole-genome sequencing (WGS) of a dead fetus and the parents was done to identify the pathogenic variation and confirmed through Sanger sequencing. WGS of dead fetus identifies a novel homozygous exonic variation (NM_017419.3:c.680G>T) in ASIC5 (acid-sensing ion channel subunit family member 5) gene; the parents are heterozygous. Newly designed ARMS PCR followed by direct sequencing confirms the presence of heterozygous in one subject and absence of homozygous novel mutation among randomly selected healthy Saudis. The second family with heterozygous was confirmed with three unexplained RPLs. Pathogenicity analysis of R227I amino acid substitution in ASIC5 protein through molecular docking and interaction analysis revealed that the mutations are highly pathogenic, decrease the stability of the protein, and prevent binding of amiloride, which is an activator to open the acid-sensing ion channel of ASIC5. The identified rare and novel autosomal recessive mutation, c.680G>T:p.R227I (ASIC5Saudi), in two families confirm the ASIC5 gene association with RPL and can be fatal to the fetus.
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