JOIN USIndian researchers develop artificial enzymes that can block HIV reactivation
There is currently no way to eliminate HIV from a patient’s body completely. Anti-HIV drugs are only successful in suppressing the virus. But city scientists have now developed artificial enzymes that can successfully block the reactivation and replication of the virus.
When anti-HIV drugs are normally used, the virus hides inside the host’s immune cells in a “latent” state. While the drugs are effective if used regularly (AIDS patients need to take them lifelong), researchers said that if a patient misses weekly doses or if the immune system is compromised or if transient viremia occurs, HIV reactivates itself — even if the patient is in therapy.
This happens when levels of toxic molecules such as hydrogen peroxide increase in the host’s cells, said associate professor Amit Singh of the Department of Microbiology and Cell Biology and Centre for Infectious Diseases Research at the Indian Institute of Science (IISc) who led the study.
“There is a connection between oxidative stress and virus reactivation. When there is higher oxidative stress, the virus emerges from hiding and begins replicating,” Dr Singh said.
Researchers realised that if they could keep the oxidative stress low, they could lock the virus in stasis. Their solution is a “nanozyme” made from vanadium pentoxide nanosheets which can mimic a natural enzyme called glutathione peroxidase that helps to reduce the oxidative stress levels in the host’s cells.
“Glutathione peroxidase converts toxic hydrogen peroxide to water and oxygen. However, generating more Glutathione peroxidase means disrupting the tightly regulated cellular redox machinery,” IISc said.
The researchers said that their nanozyme should be used in combination with anti-retroviral drugs. In studies with live HIV cells, they found this combination kept the virus suppressed for 21 days.
Significantly, when researchers “removed the anti-retroviral drugs, the virus did not come out of latency for a period of one month”, according to Dr Singh. He added that further, rigorous studies are required.
Professor Govindasamy Mugesh of the Department of Inorganic and Physical Chemistry said that the added advantage of the nanozymes is that they are stable inside biological systems and do not mediate any unwanted reactions inside the cells. “They are also easy to prepare in the lab,” he said.
While research into the enzyme has been going on since 2016, the team recently made the connection to HIV through concurrent research. In 2018, researchers under Professor Mugesh first found that the enzyme could act like a natural antioxidant enzyme and help control hydrogen peroxide levels.
The research findings were published in the journal EMBO Molecular Medicine.