Feng LiWipaporn KhanomXia SunAtchara PaemaneeSittiruk RoytrakulDecai WangDuncan R. SmithGuo Chun ZhouNanjing Tech UniversityMahidol UniversityThailand National Center for Genetic Engineering and Biotechnology2020-11-182020-11-182020-10-30Molecules (Basel, Switzerland). Vol.25, No.21 (2020)142030492-s2.0-85095593790https://repository.li.mahidol.ac.th/handle/20.500.14594/59864Andrographolide is a labdene diterpenoid with potential applications against a number of viruses, including the mosquito-transmitted dengue virus (DENV). In this study, we evaluated the anti-viral activity of three 14-aryloxy analogues (ZAD-1 to ZAD-3) of andrographolide against Zika virus (ZIKV) and DENV. Interestingly, one analogue, ZAD-1, showed better activity against both ZIKV and DENV than the parental andrographolide. A two-dimension (2D) proteomic analysis of human A549 cells treated with ZAD-1 compared to cells treated with andrographolide identified four differentially expressed proteins (heat shock 70 kDa protein 1 (HSPA1A), phosphoglycerate kinase 1 (PGK1), transketolase (TKT) and GTP-binding nuclear protein Ran (Ran)). Western blot analysis confirmed that ZAD-1 treatment downregulated expression of HSPA1A and upregulated expression of PGK1 as compared to andrographolide treatment. These results suggest that 14-aryloxy analogues of andrographolide have the potential for further development as anti-DENV and anti-ZIKV agents.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyChemistryArticleSCOPUS10.3390/molecules25215037