JBC: New Research Shows That Redoxivir Can Efficiently Inhibit SARS-CoV-2 Virus Replication

- Mar 30, 2020-

The new coronavirus SARS-CoV-2 (formerly known as 2019-nCoV) caused the 2019 coronavirus disease (COVID-19), which is now raging globally. In a new study, researchers from the University of Alberta in Canada found that the drug remdesivir (also known as GS-5734) is very effective in preventing the SARS-CoV-2 replication mechanism. The relevant research results were published online in the Journal of Biological Chemistry on April 13, 2020. The paper titled "Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency". The corresponding author of the paper is Dr. Matthias Götte, Director of the Department of Medical Microbiology and Immunology at the University of Alberta.

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Image from mBio, 2018, doi: 10.1128 / mBio.00221-18.

This paper closely follows a study published by Gotte Labs at the end of February of this year (JBC, First Published on 24 February 2020, doi: 10.1074 / jbc.AC120.013056). The study shows that this drug can strongly inhibit A related coronavirus: Middle East Respiratory Syndrome (MERS) coronavirus (MERS-CoV).

Götte said, "We are optimistic that we will observe the same results for the SARS-CoV-2 virus. The results we obtained are almost the same as the results we reported earlier for MERS-CoV, so we observed Redox Wei is a very potent coronavirus RNA polymerase inhibitor. "

This new paper by Götte shows in detail how the reducivir developed in 2014 to combat the Ebola virus outbreak worked. He likened the coronavirus RNA polymerase to the engine of this virus, responsible for synthesizing the genome of this virus. Götte said, "If this RNA polymerase is targeted, the virus cannot spread, so this is a very reasonable therapeutic target."

This new study from Götte's laboratory shows how redcivir can deceive the coronavirus by simulating the building block of the coronavirus (here, nucleotides). Götte explained, "These coronavirus RNA polymerases are so sloppy, they are deceived, so this inhibitor will be integrated many times, and the coronavirus can no longer replicate."

Götte said that the evidence from his research team and previous studies conducted in animal and cell culture models mean that redoxivir can be classified as a “direct-acting antiviral agent (direct antiviral agent) targeting SARS-CoV-2. -acting antiviral) ", the term is used for the first time to describe a class of new antiviral drugs that interfere with specific steps of the life cycle of the hepatitis C virus (HCV). He said that the discovery of direct effects has strengthened the prospects for the clinical trials of redoxivir in patients with COVID-19, which have been conducted around the world.

Although Götte said this evidence confirms the rationality of conducting clinical trials, he reminded that the results obtained in the laboratory cannot be used to predict the effect of this drug in the human body. His research was supported by grants from the Canadian Institutes of Health, Alberta Major Innovation Foundation, and Gilead Sciences Corporation, which manufactures Redcive.

The Götte laboratory has previously studied human immunodeficiency virus (HIV) and HCV, but turned to focusing on viruses with the highest epidemic potential a few years ago. The World Health Organization (WHO) released in 2015 a list of major pathogens that could cause serious outbreaks, including Ebola, Lassa and Coronavirus. Götte said, “In this sense, we are ready, because my laboratory specializes in viral polymerases.” He added that his next step will be to use his laboratory ’s tools to evaluate other Promising antiviral drugs.

He is optimistic that the unprecedented research being carried out worldwide and the high degree of cooperation between scientists will lead to the discovery of one or more effective treatments for COVID-19. He said, "We are desperate, but we still have to maintain high standards for any drugs put into clinical trials."

After comparing the potential treatment of inpatients with COVID-19 in more than a dozen countries, including Canada, redoxivir is one of several drugs that the World Health Organization is rapidly entering clinical trials. Götte said they expect to obtain important clinical trial results as early as April or May this year.

Götte said that it was disappointing that the antiviral drugs discovered during the outbreak of the severe acute respiratory syndrome (SARS) in 2003-which may also be effective for COVID-19-have never been translated into widely available treatments Drugs, mainly because of the huge cost involved in developing new drugs.

He said, "This time, it is clear that we have to cross the finish line. 10 billion US dollars, which seems to be a lot of money. However, in the context of this pandemic, considering the cost of this pandemic This is nothing. ”