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IISc research develop artificial enzymes to block HIV reactivation

To prevent reactivation and replication of the Human Immunodeficiency Virus (HIV) in the host’s immune cells, researchers at the Indian Institute of Science (IISc) have developed artificial enzymes.

These nanozymes have been formed from vanadium pentoxide nanosheets by mimicking a natural enzyme called glutathione peroxidase that helps reduce oxidative stress levels in the host’s cells, which is needed to keep the virus in check.

The study was led by Amit Singh, Associate Professor at the Department of Microbiology and Cell Biology and Centre for Infectious Diseases Research (CIDR), and Govindasamy Mugesh, Professor at the Department of Inorganic and Physical Chemistry. They have announced their findings in EMBO Molecular Medicine.

“The advantage is that the nanozymes are stable inside biological systems and do not mediate any unwanted reactions inside the cells. They are also quite easy to prepare in the lab,” said lead researcher Prof Mugesh.

IISc said, there is no way at present to eliminate HIV from a patient’s body entirely. Anti-HIV drugs are only successful in crushing the virus; they fail at destroying HIV from infected cells. When the levels of toxic molecules such as hydrogen peroxide increase in the host’s cells, leading to a state of increased oxidative stress, the virus gets “reactivated”.

Prof Singh’s team developed a biosensor to measure oxidative stress levels in HIV-infected immune cells in real-time. “We found that to come out of latency and reactivate, HIV needs very little oxidative stress,” Prof Singh said.

The only way to block reactivation is to keep the oxidative stress uniformly low. Enzymes such as glutathione peroxidase can transform toxic hydrogen peroxide to water and oxygen, the researchers had discovered.

Prof Mugesh’s group found that nanowires made of vanadium pentoxide can efficiently copy the activity of glutathione peroxidase. Singh’s lab, therefore, decided to cooperate with them.

The researchers prepared ultrathin nanosheets of vanadium pentoxide in the lab and treated HIV-infected cells with them. The sheets were found to decrease hydrogen peroxide just as completely as the natural enzyme and prevent the virus from reactivating.

“We found that these nanosheets were having some sort of direct effect where the expression of the host genes essential for virus reactivation is reduced,” explained Shalini Singh, first author and Research Associate at CIDR.

When the team treated immune cells from HIV-infected patients experiencing antiretroviral therapy (ART) with the nanozymes, latency was produced faster and consequent reactivation was crushed when treatment was stopped, showing that blending the two was more effective, she added.

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