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Replication of HIV in cells can be blocked by artificial enzymes developed by IISc researchers

According to a study published in the EMBO Molecular Medicine, researchers at the Indian Institute of Science (IISc) have developed artificial enzymes that can successfully block reactivation and replication of the Human Immunodeficiency Virus (HIV) in the host’s immune cells. The study was led by Amit Singh, Associate Professor and Wellcome Trust-DBT India Alliance Senior Fellow at the Department of Microbiology & Cell Biology and Centre for Infectious Diseases Research (CIDR), and Govindasamy Mugesh, Professor at the Department of Inorganic and Physical Chemistry.

The “nanozymes”, which are made from vanadium pentoxide nanosheets, work by mimicking a natural enzyme called glutathione peroxidase that helps reduce oxidative stress levels in the host’s cells, which is required to keep the virus in check.

The Anti-HIV drugs available in the market just suppress the virus and fail to eliminate HIV from a patient’s body completely. The virus hides inside the host’s immune cells in a “latent” state and stably maintains its reservoir. 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” ‒ it emerges from hiding and begins replicating again.

“Reactivation of latent but replication‐competent human immunodeficiency virus (HIV‐1) poses a major barrier to curing the infection. Impaired redox metabolism is one of the mechanisms of HIV‐1 reactivation; however, application of this knowledge for therapeutic benefits remains challenging due to deleterious side effects of manipulating redox physiology of the infected cells,” the study said.

The researchers prepared ultrathin nanosheets of vanadium pentoxide in the lab and treated HIV-infected cells with them. The sheets were found to reduce hydrogen peroxide just as effectively 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 undergoing antiretroviral therapy (ART) with the nanozymes, latency was induced faster and subsequent reactivation was suppressed when therapy was stopped, indicating that combining the two was more effective, she added.

Combining ART with the nanozymes also has other advantages. Some ART drugs can cause oxidative stress as a side effect, which can damage heart or kidney cells, said Amit Singh. “Adding a nanozyme like this can help in reducing the side effects caused by such ART drugs. This can improve the quality of life of HIV patients undergoing treatment,” he added.

Although the nanozymes were found to be harmless to normal cells in lab tests, Mugesh pointed out that further studies are needed to understand if they can have other effects once they are introduced inside the body. “Where will they go? Which organs will they enter? How long will they stay in the body? We need to look at all these aspects,” he explained.

Nanozymes have been explored as low‐cost alternatives to natural enzymes but their application was largely restricted to industries for chemical synthesis, detection of biomolecules, and bioremediation and was largely ignored by the biomedical community. Recent studies provide evidence for the clinical importance of artificial nanozymes in vivo. For example, ceria‐based nanoparticles (NPs) mimic superoxide dismutase (SOD) activity and exhibit neuroprotection and reduced inflammation. Similarly, iron oxide‐based nanoparticles mimic peroxidase‐like activity and protect from bacterial biofilms associated with oral infection. Moreover, ferumoxytol, an FDA approved iron oxide nanoparticle, has been shown to inhibit tumour growth in mice. Recently, vanadium pentoxide (V2O5) nanomaterials were reported to mimic glutathione peroxidase (GPX)‐like activity in vitro and protect mammalian cells from oxidative stress.

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