Bengaluru: IISc resarchers develop artificial enzymes to block replication of HIV

While eliminating HIV from a patient’s body completely is impossible as of now, anti-HIV drugs that have been developed so far are only successful in suppressing the virus. However, they fail at eradicating HIV from infected cells, the team observed.

In a path-breaking discovery, a team of researchers at the Indian Institute of Science (IISc) in Bengaluru have developed artificial enzymes that can successfully block reactivation and replication of the Human Immunodeficiency Virus (HIV) in the host’s immune cells.

According to the team, these “nanozymes”, 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 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,” Govindasamy Mugesh, Professor at the Department of Inorganic and Physical Chemistry.

While eliminating HIV from a patient’s body completely is impossible as of now, anti-HIV drugs that have been developed so far are only successful in suppressing the virus. However, they fail at eradicating HIV from infected cells, the team observed.

“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,” a statement issued by IISc mentioned.

The study, published in EMBO Molecular Medicine, 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).

It can be recalled that a team led by Singh had developed a biosensor to measure oxidative stress levels in HIV-infected immune cells in real-time some years back. “We found that to come out of latency and reactivate, HIV needs very little oxidative stress,” Singh explained.

Around the same time, Mugesh’s group had published a study showing that nanowires made of vanadium pentoxide can efficiently mimic the activity of glutathione peroxidase. Singh’s lab, therefore, decided to collaborate with them.
“We found that these nanosheets (that were prepared using vanadium pentoxide) were having some sort of direct effect where the expression of the host genes essential for virus reactivation is reduced,” Shalini Singh, first author and Research Associate at CIDR highlighted.

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 added.

According to the World Health Organisation (WHO), HIV has claimed almost 33 million lives from across the world to date. An estimated 38 million people were living with HIV at the end of 2019, statistics indicated.

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