The synthetic molecules YK51 and YK73 attenuate replication of dengue virus serotype 2
- Author:
Gan, C.S.
;
Yusof, R.
;
Othman, S.
- Publication Type:Journal Article
- From:Tropical Biomedicine
2017;34(2):270-283
- CountryMalaysia
- Language:English
-
Abstract:
Dengue virus infection has been posing alarming economic and social burden on
affected nations. It is estimated that 50-100 million dengue infections occur annually with
over 2.5 billion people at risk for endemic transmission. In the effort to develop effective
antiviral agents, we previously reported potential antiviral activities from selected array of
natural products and compounds against dengue virus serotype 2 (DV2). In this study, we
report the synthesis of two efficacious novel compounds, YK51 and YK73, and their activities
against DV2 replication. Both compounds were chemically synthesised from nicotinic acid
using a modified method for the synthesis of dihydropyridine. The products were tested with
cell-based assays against DV2 followed by a serine protease assay. As a result, both YK51 and
YK73 exhibited intriguing antiviral properties with EC50 of 3.2 and 2.4 µM, respectively. In
addition, YK51 and YK73 were found to attenuate the synthesis of intracellular viral RNA and
protect the switching of non-classic mechanism of protein translation. These compounds
demonstrated inhibitory properties toward the activity of DV2 serine protease in a dose
dependent manner. These findings demonstrate that both YK51 and YK73 serve as DV2 serine
protease inhibitors that abrogate viral RNA synthesis and translation. Further investigation
on these compounds to corroborate its therapeutic properties towards dengue is warranted.
- Full text:P020170616363727991818.pdf
