Aedes aegypti mosquitoes transmit chikungunya virus to people
A preliminary study has found that efavirenz — a non-nucleoside inhibitor of HIV virus that is used for treating HIV/AIDS — can be repurposed for the treatment of chikungunya. Currently, no antiviral compound has been approved for treating chikungunya and only a limited number of novel compounds have been tested against the virus in animal models.
Chikungunya reappeared in India in 2006 after a long gap of 20-30 years. In 2006, chikungunya virus was clinically suspected in nearly 14 million people and was laboratory-confirmed in 2,001 cases. Since 2006, chikungunya cases have been reported from various parts of India but gradually declined until 2014. Chikungunya cases have been reported in a large number of people since 2018 — over 12,000 confirmed cases in 2018 and 2019, over 11,500 cases in 2021, over 10,500 cases in 2022, and over 70,000 confirmed cases in 2024.
Researchers from the Department of Biosciences and Bioengineering at IIT Roorkee tested the efavirenz drug both in cell lines and in mouse models and found the drug to significantly reduce the viral load by inhibiting the replication of the chikungunya virus. In cell lines, the HIV/AIDS drug efavirenz inhibited the replication by almost 99% even at low micromolar concentrations. In the case of mice, the efavirenz treatment “significantly” reduced chikungunya viral load, which in turn decreased the propagation of the virus in the mice footpad. The results were published in the journal ACS Infectious Diseases.
Laboratory studies were first carried out using Vero cells. To validate the finding observed in Vero cells, the team lead by Dr. Shailly Tomar from IIT Roorkee, examined the inhibitory activity of efavirenz in human hepatic cell lines. Hepatic cell lines were chosen as chikungunya virus targets the hepatocytes — the functional cells of the liver — in the natural course of infection.
Vero cells were treated with efavirenz at different time periods of infection — from two hours before infection to zero, two, four, six, eight, 10 and 12 hours post-infection. And the drug was found to prominently and significantly inhibit virus replication up to six-eight hours post-infection. “The experiment demonstrated that the drug acts during the early phase of chikungunya replication after virus entry,” says Sanketkumar Nehul from IIT Roorkee and the first author of the paper.
“In different lab-grown cells, it was observed that efavirenz can inhibit the replication of almost 99% of the virus at low micromolar concentrations. Viral replication was also inhibited when Chikungunya-infected mice were treated with the efavirenz,” says Dr. Tomar. “It was also observed that the efavirenz is also able to inhibit the replication of Sindbis virus, which is evolutionarily closely related to the chikungunya virus.”
In mice, swelling of the limb inoculated with chikungunya virus was observed post-infection, which peaked on the second and sixth day post-infection. While earlier studies in mice have reported decrease in swelling post-treatment with other anti-chikungunya virus compounds, treatment with efavirenz led to significant increase in the swelling. According to the authors, the increased swelling of the limbs can be explained by pro-inflammatory action of efavirenz. Though treatment with efavirenz led to increased swelling, there was significant reduction in the viral load.
The paper cites a 43-year-old HIV positive person infected with chikungunya virus and who was being treated with antiretroviral drugs, including efavirenz, displaying improved condition. Though the improvement with respect to chikungunya infection cannot be completely attributed to efavirenz as he was treated with other drugs, the findings nevertheless is in line with the anti-chikungunya virus activity observed in the current study.
“Based on good pharmacokinetics properties, previous successful applications of efavirenz to treat HIV infection, and the demonstrated anti-chikungunya activity in this study, efavirenz shows high potential for repurposing against human chikungunya infections and further clinical human trials can be conducted in this direction,” Dr. Tomar says.
Published – March 15, 2025 10:45 pm IST