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Potential COVID-19 treatment of influenza drug enisamium

Researchers in Europe and the United States show the potential of the influenza drug Enisamium to treat infections with drugs that cause severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – coronavirus disease 2019 (COVID-19) I did.

Aartjante Velthuis and colleagues at the University of Cambridge, UK, showed that enisamium prevented SARS-CoV-2 replication in human cell lines and stopped viral RNA synthesis. In vitro..

In addition, in a double-blind, randomized, placebo-controlled trial of adults admitted with COVID-19, enisamium significantly reduced recovery time in patients requiring oxygen supplementation.

The drug has already been clinically approved for influenza use in 11 countries. In addition, Enisamium does not require intravenous administration and can be used outside the hospital.

Researchers state that observations indicate enisamium as a viable and accessible option for the treatment of SARS-CoV-2 infection and COVID-19.

The preprinted version of the research treatise is bioRxiv * Servers and articles have been peer reviewed.

Vaccines are available, but antivirals are still needed

Since the outbreak of COVID-19 first began in Wuhan, China, a vaccine was developed at the end of last year (2020) to prevent the spread of SARS-CoV-2, and several antiviral agents such as remdesivir were clinically used. Emergency use was approved. COVID 19 cases.

However, vaccine deployment is time consuming and current antivirals can only be given intravenously in hospitals, requiring additional strategies.

“The rapid global spread of SARS-CoV-2 requires the development of effective therapeutic interventions, and the most promising short-term strategy is to reuse existing drugs,” the team wrote.

SARS-CoV-2 RNA polymerase transcribes viral genesA few

Within the SARS-CoV-2 viral genome, two open reading frames (ORFs) – 1a and 1b – are proteolytically cleaved into two large polyproteins that produce 16 unstructured proteins (nsps). Code

One of these proteins, nsp12, is an RNA-dependent RNA polymerase that copies and transcribes the SARS-CoV-2 genome.

You need nsp7 and nsp8 to run this process on Nsp12. In vitroHowever, te Velthuis and colleagues state that Nsp12 is likely to require other nsps such as nsp9 and nsp13. In vivo processing.

According to the team, the cryo-EM structure of the SARS-CoV-2 nsp12 / 7/8 and nsp8 / 9/12/13 complexes has already been determined.

In addition, antiviral remdesivir has previously been shown to inhibit the nsp12 / 7/8 complex, and other small molecule inhibitors have been proposed as therapeutic candidates.

Where does Enisamium come from?

One drug highlighted by the World Health Organization as a potential candidate for the treatment of SARS-CoV-2 infection is enisamium.

The drug is an effective inhibitor of influenza A and B viruses approved for use against influenza in 11 countries of the Commonwealth of Independent States.

Recent studies have shown that an enisamium biotransform called VR17-04 inhibits the activity of influenza virus RNA polymerase, reduces viral shedding, and improves recovery in infected patients.

What did the researchers do?

Researchers have shown that enisamium can inhibit the growth of SARS-CoV-2 in normal human bronchial epithelial cell (NHBE) cells and a human colonic epithelial cancer cell line called Caco-2.

they again, In vitro Assay showing that the metabolite VR17-04 directly inhibits the RNA synthesis activity of the SARS-CoV-2nsp12 / 7/8 complex..

To confirm the anti-SARS-CoV-2 activity of enisamium, the team conducted a double-blind, randomized, placebo-controlled study of 373 inpatient COVID-19 patients who needed medical care with or without oxygenation. The test was conducted.

Participants received either enisamium (500 mg / dose) or placebo for 7 days.

Interim analysis showed that among those in need of oxygen supplementation (n = 77), enisamium significantly improved recovery time compared to placebo (11.1 days vs. 13.9). Day).

No significant difference in recovery time was observed in all patients (n = 373) or those who required medical care without oxygenation (n = 296).

What is the meaning of research?

Researchers say the findings suggest that enisamium is an inhibitor of SARS-CoV-2 RNA synthesis and reduces recovery time in COVID-19 patients who require oxygenation. ..

“Our observations increase the likelihood that enisamium can be used as a viable therapeutic option for SARS-CoV-2 infection,” writes te Velthuis and colleagues.

“In addition, unlike remdesivir, enisamium does not require intravenous administration, which is advantageous when used outside the hospital,” they conclude.

*Important Notices

medRxiv Publish preliminary scientific reports that should not be considered definitive as they are not peer-reviewed, guide clinical practice / health-related behaviors, and should not be treated as established information.

Potential COVID-19 treatment of influenza drug enisamium

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