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Large-Scale Drug Analysis Reveals Potential New Covid-19 Antivirals

In a series of papers, scientists identified 15 molecules that inhibit the growth of SARS-CoV-2 by blocking enzymes.

LONDON — Thousands of drugs and chemical molecules were screened and identified by the researchers at the Francis Crick Institute and the University of Dundee for potential antivirals that could be developed into new treatments for Covid-19 or in preparation for future coronavirus outbreaks. 

In a series of seven papers published in the Biochemical Journal, the scientists identified 15 molecules that inhibit the growth of SARS-CoV-2 by blocking different enzymes involved in its replication.

While Covid-19 vaccines are being rolled out, there are still few drug options that can be used to treat patients with the virus, reduce symptoms, and speed up recovery time. These treatments are essential for groups where the vaccines are less effective, such as some patients with blood cancers.

“We have developed a chemical toolbox of information about potential new Covid-19 drugs,” said John Diffley, lead author of the papers and associate research director at the Francis Crick Institute. 

“We hope this attracts attention from scientists with the drug development and clinical expertise needed to test these further and ultimately see if any could become safe and effective treatments for Covid-19 patients.”

The researchers developed and ran tests for around 5,000 molecules provided by Crick’s High Throughput Screening team to see if any of these effectively blocked the functioning of any of seven SARS-CoV-2 enzymes. The tests were based on fluorescent changes with a unique imaging tool detecting if enzymes had been affected.

They then validated and tested the potential inhibitors against SARS-CoV-2 in the lab to determine if they effectively slowed viral growth. The team found at least one inhibitor for all seven enzymes.

Three of the molecules identified are existing drugs used to treat other diseases. 

Lomeguatrib is used in melanoma and has few side effects. Suramin is a treatment for African sleeping sickness and river blindness, and trifluperidol is used in cases of mania and schizophrenia. As there are existing safety data on these drugs, it may be possible to develop into SARS-CoV-2 antivirals more quickly.

The 15 molecules were also tested in combination with Remdesivir, and an antiviral was used to treat patients with Covid-19. Four of these, all of which target the SARS-CoV-2 enzyme Nsp14 mRNA Cap methyltransferase, were found to improve the effectiveness of this antiviral in lab tests.

The scientists now plan to run tests to see if any pairing of the 15 molecules they identified decreases the virus’ growth more than if they are used alone. Targeting enzymes involved in virus replication could also help prepare for future viral pandemics.

“Proteins on the outside of viruses evolve rapidly, but within different classes of viruses are well-conserved proteins that change very little with time,” said Diffley.

“If we can develop drugs that inhibit these proteins, in the situation of a future pandemic, they could provide a valuable first line of defense, before vaccines become available.”

As per the World Health Organization, globally, there have been 182,319,261 confirmed cases of Covid-19, including 3,954,324 deaths. As of June 30, 2021, a total of 2,950,104,812 vaccine doses have been administered.

(With Inputs from ANI)

(Edited by Amrita Das and Saptak Datta)

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