By repurposing the HIV treatment rilpivirine, investigators have opened up possibilities for treating Zika virus and other flavivirus infections which overlap with HIV.
While Zika virus has receded from headlines since prominent outbreaks in 2016, it remains a danger for residents and travelers in countries with certain climates and mosquito species. As of October 2019, 10 Zika cases have been reported in the United States in travelers returning from affected areas. The virus was previously isolated to regions of Asia and Africa, but can now also be found in South America.
Investigators are hopeful that repurposing an existing drug used in HIV treatment could be a possible option to treat Zika and other flavivirus infections that share overlap with HIV.
Investigators at the Lewis Katz School of Medicine at Temple University published a study in Molecular Therapy showing that a drug used in HIV treatment also suppresses Zika virus infections. The investigators demonstrated that rilpivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), targets enzymes that both Zika and HIV depend on for replication. These enzymes are also found in other flavivirus infections, such as dengue and hepatitis C.
The enzyme Zika uses to replicate is called non-structural protein 5 RNA-dependent RNA polymerase (NS5 RdRp). The study team used computational studies to show that rilpivirine stops viral replication by binding to the NS5 domain.
"By discovering that rilpivirine blocks Zika virus replication by binding to an RNA polymerase enzyme common to a family of RNA viruses, we've opened the way to potentially being able to treat multiple RNA virus infections using the same strategy," study author Kamel Khalili, PhD, Laura H. Carnell professor and chair of the Department of Neuroscience, director of the Center for Neurovirology, and director of the Comprehensive NeuroAIDS Center at the Lewis Katz School of Medicine, said in a press release.
After experiments in cell models, the study team experimented with mice. The mice were infected with Zika virus via their footpads, mirroring how a person is infected by a mosquito bite. Mice infected with Zika virus typically become ill within a week and eventually die. When treated with rilpivirine, however, the animals survived. The small animal model study demonstrated that rilpivirine suppresses viral replication, protected neurons from apoptosis and necrosis, decreased brain inflammation, and reversed Zika-associated mortality.
The study authors recommended that future research investigate if people with HIV treated with rilpivirine are at a lower risk of Zika infection. They also wrote that “future studies will include in vivo studies utilizing other NNRTIs that were found to be suppressive in vitro, including efavirenz and ETR [etravirine].” Flavivirus infections tend to overlap regionally and temporally, broadening the potential impact of treatments that are effective across viruses.
Rilpivirine was approved by the US Food and Drug Administration in 2011 for treatment-naïve patients with HIV-1. It is prescribed both independently and in single-pill combinations with other HIV medications. Rilpivirine is currently being studied in combination with cabotegravir in the development of long-acting injectables which could potentially replace daily oral medication for some patients with HIV.