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Updated: Jul 12, 2026
Zika Virus Infectious Cell Culture System and the In Vitro Prophylactic Effect of Interferons
Published on: August 23, 2016
Ivermectin Inhibits Zika Virus Replication in Vitro But Does Not Prevent Zika Virus Infection in Rhesus Macaques
Thomas S Cotrone1, Kevin Kobylinski2, Alongkot Ponlawat2
1Department of Virology, Walter Reed Army Institute of Research-Armed Forces Research Institute of Medical Science (WRAIR-AFRIMS), Bangkok, Thailand.
Abstract:
Zika virus (ZIKV) outbreaks occur sporadically in tropical and subtropical regions. At present, there are no licensed vaccines or specific treatments available for ZIKV. Ivermectin is approved for use in humans as an antiparasitic drug. In this study, we conducted in vitro cell culture and in vivo experiments in rhesus macaque hosts and Aedes aegypti vectors to investigate the potential of ivermectin as an inhibitor of ZIKV infection. In LLC-MK2 mammalian cells, ivermectin inhibited ZIKV growth in vitro with 50% inhibitory concentration (IC50) values in the ranges of 7.4-21.3 µM and 4.0-11.6 µM for African and Asian genotypes, respectively. In C6/36 mosquito cells, ivermectin inhibited ZIKV growth in vitro with IC50 values in the ranges of 10.1-17.4 µM and 8.0-15.6 µM for the African and Asian genotypes, respectively. Despite these in vitro results, high-dose ivermectin prophylaxis (1.2 mg/kg for 3 consecutive days) failed to prevent ZIKV infection in rhesus macaque and did not alter ZIKV IgM antibody production. The secondary transfer of ivermectin from nonhuman primate blood to mosquito vectors at 3 days post-ZIKV inoculation and after the last dose of ivermectin administration showed no reduction in ZIKV replication in mosquitoes. However, mosquito survival rates were significantly (P <0.0001) lower after exposure to ivermectin, thereby potentially impacting ZIKV transmission through increased vector mortality. However, further investigation is needed to determine dosing regimens that may realize these effects in vivo.
Insights
Ivermectin showed in vitro activity against Zika virus (ZIKV) but failed to prevent ZIKV infection in rhesus macaques. However, ivermectin significantly reduced mosquito survival, potentially impacting ZIKV transmission.
Area of Science:
- Virology
- Infectious Diseases
- Drug Discovery
Background:
- Zika virus (ZIKV) outbreaks pose a significant public health threat in tropical and subtropical regions.
- Currently, no licensed vaccines or specific antiviral treatments are available for ZIKV infection.
- Ivermectin, an established antiparasitic drug, is being investigated for potential antiviral properties.
Purpose of the Study:
- To evaluate the efficacy of ivermectin as an inhibitor of Zika virus (ZIKV) infection.
- To assess ivermectin's antiviral activity in both cell culture and animal models, including the mosquito vector.
Main Methods:
- In vitro studies using LLC-MK2 mammalian cells and C6/36 mosquito cells to determine ivermectin's 50% inhibitory concentration (IC50) against ZIKV genotypes.
- In vivo experiments in rhesus macaques to assess ivermectin's prophylactic efficacy against ZIKV infection and its effect on antibody production.
- Evaluation of secondary ivermectin transfer from infected nonhuman primate blood to Aedes aegypti mosquitoes and its impact on ZIKV replication and vector survival.
Main Results:
- Ivermectin demonstrated in vitro inhibition of ZIKV replication in both mammalian and mosquito cell lines, with varying IC50 values for different genotypes.
- High-dose ivermectin prophylaxis in rhesus macaques did not prevent ZIKV infection or alter IgM antibody responses.
- Secondary transfer of ivermectin did not reduce ZIKV replication in mosquitoes, but significantly decreased mosquito survival rates.
Conclusions:
- While ivermectin exhibits in vitro antiviral activity against ZIKV, it is not effective in preventing ZIKV infection in a rhesus macaque model at the tested dosage.
- Ivermectin's significant impact on vector mortality suggests a potential indirect role in controlling ZIKV transmission by reducing mosquito populations.
- Further research is required to explore optimal dosing strategies for ivermectin to potentially leverage its vector control effects in vivo.
