Núbia Boechat

The purpose of this study was to prepare various 4-substituted N-phenyl-1,2,3-triazole derivatives using click chemistry. The derivatives were screened in vitro for antimicrobial activity against Mycobacterium tuberculosis strain H37Rv (ATCC 27294) using the Alamar Blue susceptibility test. The activity was expressed as the minimum inhibitory concentration (MIC) in μg/mL (μM). Derivatives of isoniazid (INH), (E)-N'-[(1-aryl)-1H-1,2,3-triazole-4-yl)methylene] isonicotinoyl hydrazides, exhibited significant activity with MIC values ranging from 2.5 to 0.62 μg/mL. In addition, they displayed low cytotoxicity against liver cells (hepatoma HepG2) and kidney cells (BGM), thereby providing a high therapeutic index. The results demonstrated the potential and importance of developing new INH derivatives to treat mycobacterial infections.

Zika virus (ZIKV) is a member of the Flaviviridae family, along with other agents of clinical significance such as dengue (DENV) and hepatitis C (HCV) viruses. Since ZIKV causes neurological disorders during fetal development and in adulthood, antiviral drugs are necessary. Sofosbuvir is clinically approved for use against HCV and targets the protein that is most conserved among the members of the Flaviviridae family, the viral RNA polymerase. Indeed, we found that sofosbuvir inhibits ZIKV RNA polymerase, targeting conserved amino acid residues. Sofosbuvir inhibited ZIKV replication in different cellular systems, such as hepatoma (Huh-7) cells, neuroblastoma (SH-Sy5y) cells, neural stem cells (NSC) and brain organoids. In addition to the direct inhibition of the viral RNA polymerase, we observed that sofosbuvir also induced an increase in A-to-G mutations in the viral genome. Together, our data highlight a potential secondary use of sofosbuvir, an anti-HCV drug, against ZIKV.