IISc Develops Artificial Enzyme To Block HIV Reactivation In AIDS Patients

The Indian Institute of Science (IISc), India's premier destination for advanced science and technology research, said that its researchers have developed artificial enzymes that can successfully block reactivation and replication of the Human Immunodeficiency Virus (HIV) in the host¡¯s immune cells.

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How does it work

These ¡°nanozymes¡±, which are made from vanadium pentoxide nanosheets, bolsters the anti©\HIV potential of immune cells by mimicking a natural enzyme called glutathione peroxidase that helps reduce oxidative stress levels in the host¡¯s cells. This is required to keep the virus in check.

The study, published in "Embo Molecular Medicine" journal, was led by Microbiology department's associate professor Amit Singh and inorganic and physical chemistry department's professor Govindaswamy Mugesh.

¡°The advantage is that the nanozymes are stable inside biological systems and do not mediate any unwanted reactions inside the cells,¡± says Mugesh. ¡°They are also quite easy to prepare in the lab.¡±

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The HIV virus can only be suppressed

It should be noted that current processes can¡¯t completely remove HIV from a patient¡¯s body and that anti-HIV drugs can only suppress the virus inside infected cells.

"The virus hides inside immune cells in a 'latent' state and maintains its reservoir," said the study. ¡°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¡± and begins replicating again.¡±

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Joining forces

Earlier, 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," said Singh.

One way to prevent reactivation is to keep the oxidative stress low, which would 'lock' the virus in a permanent latent state. Enzymes such as glutathione peroxidase convert toxic hydrogen peroxide to water and oxygen and therefore are essential for this process. However, its application remained a worry as these enzymes could disrupt the tightly regulated cellular antioxidant systems.

Around the same time, Mugesh¡¯s group published a study showing that nanowires made of vanadium pentoxide can efficiently mimic the activity of glutathione peroxidase. The collaboration between both teams was only natural.

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The teams prepared ultrathin nanosheets of vanadium pentoxide in the lab and treated HIV-infected cells with them. The nanosheets were found to reduce hydrogen peroxide as effectively as a natural enzyme and prevent the virus from reactivating.

Combining antiretroviral therapy (ART) with nanozymes also has other advantages. "Adding a nanozyme can help reduce side-effects caused by such ART drugs. It can also improve the quality of life of HIV patients undergoing treatment," Mugesh added.