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IISc develops nanozymes that can block HIV reactivation | India News

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BENGALURU: The Indian Institute of Science (IISc) said Thursday that its researchers have developed artificial enzymes that can successfully block the reactivation and replication of Human Immunodeficiency Virus (HIV) in host immune cells.
“Made from vanadium pentoxide nanofilms, these ‘nanozymes’ work by mimicking a natural enzyme called glutathione peroxidase that helps reduce levels of oxidative stress in host cells, which is necessary to keep the virus in check,” said IISc, and added that the research findings have been published in the journal EMBO Molecular Medicine.
The research was led by Amit Singh, Associate Professor and Principal Investigator of the Wellcome Trust-DBT India Alliance in the Department of Microbiology and Cell Biology and Center for Infectious Diseases Research (CIDR), and Govindasamy Mugesh, Professor in the Department of Inorganic Chemistry and Physical.
“The advantage is that nanozymes are stable within biological systems and do not mediate unwanted reactions within cells. They are also quite easy to prepare in the laboratory, ”says Mugesh.
A statement from IISc says that there is currently no way to completely remove HIV from a patient’s body.
“HIV drugs are only successful in suppressing the virus; they fail to eradicate HIV from infected cells. The virus hides within the host’s immune cells in a ‘latent’ state and stably maintains its reservoir, “he adds.
According to IISc, when levels of toxic molecules like hydrogen peroxide rise in host cells, leading to a state of increased oxidative stress, the virus “reactivates”, comes out of hiding and begins to replicate again.
A few years ago, Singh’s team developed a biosensor to measure levels of oxidative stress in HIV-infected immune cells in real time. “We found that to get out of dormancy and reactivate, HIV needs very little oxidative stress,” he says.
One way to prevent reactivation, the statement reads, is to keep oxidative stress constantly low, which would “lock” the virus into a permanent state of dormancy. Enzymes such as glutathione peroxidase are essential for this process, as they convert toxic hydrogen peroxide into water and oxygen.
However, inducing host cells to produce more of these enzymes could disrupt the tightly regulated cellular redox machinery.
“Around the same time, Mugesh’s group published a study showing that nanowires made from vanadium pentoxide can efficiently mimic glutathione peroxidase activity. Singh’s lab therefore decided to collaborate with them, ”said IISc.
The researchers made ultrafine nano-sheets in the lab and treated HIV-infected cells with them, and the IISc said the sheets were found to reduce hydrogen peroxide as effectively as the natural enzyme and prevent the virus from reactivated.
“We found that these nanosheets had some kind of direct effect in which the expression of host genes essential for virus reactivation is reduced,” said Shalini Singh, first author and research associate at CIDR.
When the team treated immune cells from HIV-infected patients undergoing antiretroviral therapy (ART) with the nanozymes, latency was induced faster and subsequent reactivation was suppressed when therapy was stopped, indicating that the combination of the two it was more effective, he adds.
The combination of ART with nanozymes also has other advantages. Some ART medications can cause oxidative stress as a side effect, which can damage heart or kidney cells, says Amit Singh. “Adding a nanozyme like this can help reduce the side effects caused by these ART drugs.” This can improve the quality of life for HIV patients receiving treatment, the statement added.
Although nanozymes were found to be harmless to normal cells in laboratory tests, Mugesh notes that more studies are needed to understand whether they may have other effects once they are introduced into the body. “Where will they go? What organs will they enter? How long will they stay in the body? We have to analyze all these aspects,” he explains.

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