Table 1.
Direct-acting antivirals against chikungunya virus.
| Antiviral agent | Mechanism of action | In vitro efficacy | In vivo efficacy | References |
|---|---|---|---|---|
| Chloroquine | Inhibition of fusion of the viral E1 protein with the endosomal membrane by raising the endosomal pH | Inhibition of CHIKV infection in Vero A cells | No significant efficacy in a macaque model or clinical trials in CHIKV infected patients | Chopra et al., 2014, Khan et al., 2010 and Roques et al. (2007) |
| Arbidol | Interference with the binding of CHIKV to host receptors and alteration of cellular membranes | Inhibition of CHIKV infection in MRC-5 cells (EC50 = 12 μM) | Not determined | Delogu et al. (2011) |
| Flavaglines | Interference with the binding of CHIKV Prohibitin-1 | Moderate antiviral effect on CHIKV replication in HEK293T/17 cells (EC50 of FL3 = 22.4 nM) | Not determined | Wintachai et al. (2015) |
| SiRNAs targeting nsP1, E2 | Inhibition of protein synthesis | Inhibition of CHIKV replication in Vero-E6 cells (>90%) | Complete inhibition of CHIKV replication in infected Swiss albino and C57 BL/6 mice when administered 3 days post-infection | Parashar et al. (2013) |
| Harringtonine and homoharringtonine | Inhibition of protein synthesis | Inhibition of CHIKV replication in BHK21 cells (EC50 = 0.24 μM) | Not determined | Kaur et al. (2013) |
| Arylalkylidene derivatives of 1,3-thiazolidin-4-one | Inhibition of CHIKV nsP2 protease activity | Inhibition of CHIKV replication in Vero A cells (EC50 of the best compound = 0.42 μM) | Not determined | Jadav et al. (2015) |
| Ribavirin | Inhibition of viral genome replication, mostly via GTP pools depletion | Inhibition of CHIKV replication in Vero cells (EC50 = 341 μM). Synergistic inhibitory effect in combination with IFN-α2b and doxycycline | Reduced the viral load and inflammation in infected ICR mice when combined with doxycycline | Briolant et al. (2004) and Rothan et al. (2015) |
| 6-Azauridine | Inhibition of orotidine monophosphate decarboxylase enzyme (depletion of UTP pools) | Inhibition of CHIKV replication in Vero cells (EC50 = 0.82 μM) | Not determined | Briolant et al. (2004) |
| Favipiravir (T-705) | Inhibition of viral genome replication | Inhibition of CHIKV-induced CPE in Vero A cells (EC50 = 25 μM) | Reduction of the mortality rate in infected AG129 mice with >50% and protection from neurological disease | Delang et al. (2014) |
| Monoclonal antibody C9 | Interaction with CHIKV E2 glycoprotein | Neutralization of CHIKV pseudovirions in HEK293T cells and replication-competent CHIKV in Vero cells | As prophylaxis: complete protection of infected C57BL/6 mice from arthritis and viremia | Selvarajah et al. (2013) |
| As therapy: 100% survival of CHIKV infected mice when given at 8 or 18 h post infection |