Antiviral activity of N-substituted 5-(Phenylamino) uracil derivatives against chikungunya virus / Noor Farah Omar Ahmad

Chikungunya virus (CHIKV), is an arthropod-borne disease that causes Chikungunya fever. Currently, there is no available drug or vaccine to treat the infected CHIKV patients. Based on literature, novel N-substituted 5-(phenylamino)uracil derivatives exhibit inhibitory effects against HIV and Hepatitis C virus but not yet been tested on CHIKV. The half maximal cytotoxic concentration (CC₅₀) of six 5-substituted(phenylamino) uracil and five 2,4-dioxo-3,4-dihydropyrimidine acetic acid compounds were at 200 µM and 800 µM respectively. Two compounds (Z214 and Z364) exhibited the best antiviral activity at concentration of 50 μM and 100 μM. Time-addition assay revealed that the inhibition was most efficient when Z214 (50 µΜ) and Z364 (100 μM) were added at 4 hour of post-infection (hpi) and at 6 hpi. This suggests that, these compounds have inhibitory effect as anti-CHIKV inhibitors at post-entry step of CHIKV replication cycle. Prophylactic treatment showed a 50 decrease in number of CHIKV plaques when Z214 (50 µM) and Z364 (100 μM) were added 5 hours before infection by 100% and 71% ± 7.01 respectively. Z214 and Z354 exhibited a significant effect against CHIKV attachment and adsorption to the Vero cells at all tested concentrations (1.56 µM to 100 µM) as compared to the virus control. Both compounds exhibited inhibition against CHIKV internalization when the compounds (at all tested concentration ranging from 1.56 µM to 100 µM) were added during virus internalization. In conclusion, these compounds under novel Nsubstituted 5-(phenylamino)uracil derivatives exhibited promising antiviral activity for Chikungunya virus and it could be further studied.