Researchers identify potential new antiviral drugs for COVID-19


Transmission electron micrograph of SARS-CoV-2 virus, isolated from a patient. Image captured and enhanced in color at NIAID’s Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

The experimental drug TEMPOL may be a promising oral antiviral treatment for COVID-19, suggests a cell culture study conducted by researchers at the National Institutes of Health. TEMPOL may limit SARS-CoV-2 infection by affecting the activity of a viral enzyme called RNA replicase. The work was led by researchers from NIH’s National Institute of Child Health and Human Development (NICHD), Eunice Kennedy Shriver. The study appears in Science.

“We urgently need additional effective and affordable treatments for COVID-19,” said Diana W. Bianchi, MD, director of NICHD. “An oral drug that prevents SARS-CoV-2 replication would be an important tool in reducing the severity of the disease.”

The study team was led by Tracey A. Rouault, MD, head of the NICHD section on human iron metabolism. He discovered the effectiveness of TEMPOL by evaluating a more basic question about how the virus uses its RNA replicase, an enzyme that allows SARS-CoV-2 to replicate its genome and make copies of it once inside a cell. .

The researchers checked whether RNA replicase (specifically the nsp12 subunit of the enzyme) requires iron-sulfur clusters for structural support. Their findings indicate that SARS-CoV-2 RNA replicase requires two iron-sulfur clusters to function optimally. Previous studies had mistakenly identified these iron-sulfur binding sites for zinc binding sites, probably because iron-sulfur clusters degrade easily under standard experimental conditions.

Identifying this feature of RNA replicase also allows researchers to exploit a weakness of the virus. TEMPOL can degrade iron-sulfur clusters and previous research by the Rouault Lab has shown that the drug can be effective in other diseases involving iron-sulfur groups. In cell culture experiments with live SARS-CoV-2 virus, the study team found that the drug can inhibit viral replication.

Based on previous studies with TEMPOL in other animal diseases, the study authors noted that the doses of TEMPOL used in their antiviral experiments could probably be achieved in tissues that are primary targets of the virus, such as glands. salivary glands and lungs.

“Given the safety profile of TEMPOL and the dose considered therapeutic in our study, we look forward to it,” said Drs. Rouault. “Despite this, are needed to determine if the file is effective in patients, especially at the beginning of the course of the disease when the it begins to reproduce “.

The study team plans to conduct additional animal studies and look for opportunities to evaluate TEMPOL in a COVID-19 clinical study.

Cube-shaped iron-sulfur clusters maintain a multiple bond between iron and nitrogen

More information:
“SARS-CoV-2 RNA-dependent RNA polymerase Fe-S cofactors are possible antiviral targets,” Science (2021).… 1126 / science.abi5224

Citation: Researchers identify new potential antiviral drugs for COVID-19 (2021, June 3) recovered on June 3, 2021 at .html

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