Figure 2: Mechanism of action of the MADTP series.
From: The viral capping enzyme nsP1: a novel target for the inhibition of chikungunya virus infection
(a) Huh 7.5.1 cells treated with different MADTP compounds were infected with CHIKV pseudoparticles. Arbidol and chloroquine were used as positive controls. The entry of CHIKVpp was determined by measuring the luciferase activity. The average values ± SD of three independent experiments are shown. (b) Cells were transfected with a replication-deficient CHIKV RNA encoding an nsP3-Rluc fusion protein, in the presence or absence of MADTP-314. Subsequently, luciferase activity was determined at 2.5, 5 and 7.5 h post-transfection. (c) CHIKV-infected Vero E6 cells (MOI 5), treated with 50, 100 and 250 μM MADTP-314, were metabolically labeled with 3H-uridine from 6–7 h p.i. Total RNA was isolated and separated by denaturing agarose gel electrophoresis, followed by fluorographic detection of 3H-labeled RNA. (d) In vitro RNA synthesizing activity of isolated CHIKV RTCs in the presence or absence of 250 μM MADTP-314, quantified by measuring the incorporation of 32P-CTP. RNA II is a 7.5 kb CHIKV RNA that corresponds to the 5′-proximal 7.5 kb of the CHIKV genome up to the subgenomic promoter region17.
