In-depth study identifies 13 potential anti-COVID drugs

The availability of COVID vaccines and the administration of the first doses in recent months have allowed many countries to start expanding their vaccination coverage in a bid to stem the pandemic. However, while vaccines are effective in prevention, there are still no effective therapies to fight the infection. Recently, a team of researchers from the Scripps Research analyzed the ReFRAME drug database for promising molecules. After laboratory tests, they identified 13 drugs with strong anti-COVID potential.

Using the world’s most comprehensive drug reassignment collection for anti-COVID-19 therapies, scientists have identified 90 existing drugs or drug candidates with antiviral activity against the coronavirus causing the ongoing global pandemic .

Among these compounds, the study of Scripps Research identified four clinically approved drugs and nine compounds in other stages of development with high potential for reuse as oral anti-COVID-19 drugs, according to results published in the journal Nature Communications.

Of the drugs that prevented the coronavirus from replicating in human cells, 19 were found to work in concert (or increased activity) with remdesivir, an antiviral therapy approved for the treatment of COVID-19. ” Although we now have effective COVID-19 vaccines, we still lack highly effective antiviral drugs that can prevent infections or keep them from getting worse. », Explains Peter Schultz, president of Scripps Research.

Our results raise the possibility of a number of promising ways to reuse existing oral drugs with efficacy against SARS-CoV-2. We have identified promising existing drugs and are also using our findings to develop optimized antivirals that will be more effective against SARS-CoV-2, including drug-resistant variants and strains, as well as other coronaviruses that currently exist. or could emerge in the future “.

Molecules directly tested in the laboratory

As part of a collaboration between Calibr, the drug discovery division of Scripps Research, and a team of researchers from the institute’s immunology and microbiology department, the study tested more than 12,000 drugs in two different types of human cells infected with SARS-CoV-2.

The drugs used in the study were from the ReFRAME drug reuse library, which was established by Calibr in 2018 with support from the Bill & Melinda Gates Foundation to address urgent unmet medical needs, especially tropical diseases. neglected. The collection contains FDA approved drugs and other investigational compounds that have been tested for safety in humans.

Among the drugs tested, the MK-4482 molecule showed potent antiviral action against SARS-CoV-2 in tests on golden hamsters. The lung tissue sample shown below shows the effectiveness of MK-4482 in blocking viral replication. © Malina A. Bakowski et al. 2021

In the study, scientists treated two different types of SARS-CoV-2 infected human cells grown in the lab with each of ReFRAME’s 12,000 drugs. After 24 or 48 hours, they measured the level of viral infection in the cells to determine if the drugs were preventing the virus from replicating. In some cases, they applied two drugs at a time to see if the compounds would work together against the virus.

Some of the most effective antiviral strategies are cocktails in which patients are given several different drugs to fight infection, such as those used to treat HIV infections. Says Thomas Rogers, professor in the Department of Immunology and Microbiology.

Thirteen antiviral molecules and nineteen synergistic molecules

Out of the thousands of drugs screened, the researchers identified a total of 90 compounds that prevented SARS-CoV-2 from replicating in at least one of the human cell lines. Of these, 13 had the highest potential for reuse as anti-COVID-19 therapies, based on their potency, cell line independent activity, pharmacokinetic properties, and human safety profiles. Four of the drugs – halofantrine, nelfinavir, simeprevir and manidipine – are already approved by the FDA and nine more are in various stages of the drug development process.

From the drug combinations, the researchers found 19 drugs that had an additive effect when given with remdesivir, the antiviral produced by the pharmaceutical company Gilead that is approved by the FDA for use in patients diagnosed with COVID-19. An additive effect means that the drugs were both active against the virus when applied together.

Two additional drugs have a greater synergistic effect on remdesivir, which means that the drugs increased the ability of remdesivir to suppress the virus. These two drugs were riboprine, a compound that has been tested as a preventative against nausea and surgical infections, and 10-deazaminopterin, a derivative of folic acid.

Sources: Nature Communications

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