Designing an HCV diagnostic kit for common genotypes of the virus in Iran based on conserved regions of core, NS3-protease, NS4A/B, and NS5A/B antigens: an in silico approach

Hepatitis C virus (HCV) is a life-threatening virus that causes liver infection. If it is not detected in an early phase, the virus can lead to severe liver damages, including hepatic fibrosis, liver cirrhosis, and hepatocellular carcinoma. Today, computational design of the HCV diagnostic kit is employed to increase the specificity and sensitivity of the ELISA (enzyme-linked immunosorbent assay) diagnosis method according to the specific genotypes of the virus in each geographical region as well as to reduce costs in developing and low-income countries. The aim of this study was to design a multi-epitope protein from common HCV genotypes in Iran (1a, 1b, and 3a). For this purpose, potential immunodominant epitopes and highly antigenic regions were identified for six antigenic proteins and all of the segments were joined using a proper linker. The physico-chemical characteristics of the designed multi-epitope protein were evaluated and tertiary structures of the construct were modeled. Then, the models were evaluated and the best one was determined. Finally, the sequence of the protein was reverse-translated and optimized for high expression in E. coli expression host. The findings of the present study indicated that the designed construct could detect the common HCV genotypes in Iran with high sensitivity and specificity

Synthesis and tyrosinase inhibitory activities of novel isopropylquinazolinones

Abstract To find new anti-browning and whitening agents in this study, new series of isopropylquinazolinone derivatives were designed and synthesized. All derivatives were evaluated as possible tyrosinase inhibitors and compound 9q bearing 4-fluorobenzyl moieties at the R position exhibited the best potencies with an IC50 value of 34.67 ± 3.68 µM. The kinetic evaluations of 9q as the most potent derivatives recorded mix-type inhibition. Compounds 9o and 9q also exhibited potent antioxidant capacity with IC50 values of 38.81 and 40.73 µM, respectively confirming their antioxidant potential. Molecular docking studies of 9q as the most potent derivative were exacuated and it was shown that quinazolinone and acetamide moieties of compound 9q participated in interaction with critical His residues of the binding site. The obtained results demonstrated that the 9q can be considered a suitable pharmacophore to develop potent tyrosinase inhibitors