The evolution of bias in synonymous codon usage in chosen monkeypox viral genomes and the factors influencing its diversification have not been reported so far. In this study, various trends associated with synonymous codon usage in chosen monkeypox viral genomes were investigated, and the results are reported. Identification of factors that influence codon usage in chosen monkeypox viral genomes was done using various codon usage indices, such as the relative synonymous codon usage, the effective number of codons, and the codon adaptation index. The Spearman rank correlation analysis and a correspondence analysis were used for correlating various factors with codon usage. The results revealed that mutational pressure due to compositional constraints, gene expression level, and selection at the codon level for utilization of putative optimal codons are major factors influencing synonymous codon usage bias in monkeypox viral genomes. A cluster analysis of relative synonymous codon usage values revealed a grouping of more virulent strains as one major cluster (Central African strains) and a grouping of less virulent strains (West African strains) as another major cluster, indicating a relationship between virulence and synonymous codon usage bias. This study concluded that a balance between the mutational pressure acting at the base composition level and the selection pressure acting at the amino acid level frames synonymous codon usage bias in the chosen monkeypox viruses. The natural selection from the host does not seem to have influenced the synonymous codon usage bias in the analyzed monkeypox viral genomes.
Background Oral administration of biguanides (metformin) and sulfonylureas (gliclazide) are the most common approach of management of type 2 diabetes in humans. Among these diabetic patients, approximately 40–60% suffers from hypertension. Hence, the need of the day is application of polytherapy. A major challenge in polytherapy is the drug-drug interactions that may arise. Hence, this study is focused to develop a reverse phase high-performance liquid chromatography (RP-HPLC) method for concurrent estimation of diabetic drug metformin and hypertension drug valsartan using C18 column and find any possible pharmacokinetic interactions between the two drug combinations strategies, i.e., metformin-valsartan and gliclazide-valsartan in streptozotocin-induced diabetic rats. Result The bioanalysis of drug-drug interaction pharmacokinetic result showed no significant difference in the tmax of single treatment of gliclazide and single treatment of metformin or upon co-administration with valsartan. Conclusion Our study has shown that polytherapy of valsartan, a drug administered for hypertension along with hypoglycemic drugs metformin and gliclazide, can be advantageous and safe in patients suffering from both diabetes and hypertension.
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