The COVID-19 pandemic continues to steamroll populations of many countries, and drive efforts to find a treatment, cure, or vaccine. The drug most recently approved by the FDA for emergency use is Gilead Sciences’ antiviral drug Remdesivir. What is Remdesivir and why is it considered to have potential against the SARS-CoV2 virus?

Remdesivir is an experimental drug in the family known as nucleoside or nucleotide analogues. A nucleoside is a compound found in DNA and RNA. An analogue is anything seen to be comparable to another.  Nucleoside analogues resemble naturally occurring compounds found in viral and human genetic material.

Remdesivir is comparable in structure to genetic building blocks. The reason nucleoside analogues are so effective in dealing with some medical issues, however, doesn’t focus on the similarities so much as the slight differences between the drug and natural nucleosides.

If an organism like a virus incorporates a nucleoside analogue drug into its genetic material, rather than the real thing, even small changes to the structure of these building blocks prevents the mechanism of viral replication from happening.

This is what seems to be the case with Remdesivir and COVID-19. Remdesivir works by blocking the coronavirus’s genetic copier called RNA polymerase. This enzyme is required for SARS-CoV2 to replicate its RNA genetic material and multiply.

Aside: Unlike humans, almost all viruses have either DNA or RNA, but not both.

Remdesivir works when the enzyme replicating the genetic material for a new generation of viruses accidentally grabs the analogue drug rather than the natural molecule and incorporates it into the growing RNA strand. Doing this essentially derails the viral train and blocks the RNA from completing the process of making new viruses while not harming normal cells. That means no newborn viruses looking for new cells to invade.

Remdesivir originally was found during a drug discovery program at Gilead Sciences to search for inhibitors of hepatitis C, another RNA virus. Gilead ultimately chose a different drug for hepatitis but decided to test it against other viruses. Remdesivir exhibited questionable medicinal benefit against Ebola, but did turn out to have some success against coronaviruses like MERS (Middle East Respiratory Syndrome) and others.

According to the National Institute of Allergy and Infectious Diseases, patients who received Remdesivir had a faster recovery compared to those who received placebo: 11 days compared with 15 days. That’s four days less in the hospital, a big deal when you think of saving bed and ventilator space, personal protection gear, and, most importantly, human suffering. Results also suggested a survival benefit, with a death rate of 8.0% for the group receiving Remdesivir versus 11.6% for the placebo group.

While these results are preliminary, there are all sorts of clinical trials underway across the world. Infectious Disease expert Dr. Anthony Fauci says “the antiviral drug Remdesivir is the first step in what we project will be better and better drugs coming along”. He also warned: “This is not the total answer.”

Still, that’s more than he was willing to say about hydroxyquinolone, the much less expensive anti-malarial drug often used in combination with zinc and the antibiotic azithromycin. That drug was described by Dr. Fauci as having only anecdotal (that is, personal observation and opinion) evidence for its effectiveness. It has recently been criticized because of the risk of heart complications at higher doses, but may be of help in some patients; it is still has an FDA emergency use authorization for compassionate use.

Of other studies that have been reported so far, some demonstrate that Remdesivir works in sick COVID-19 patients, while others report that it doesn’t seem to show as significant an effect.

All this means that Remdesivir has potential to be helpful in severe cases of COVID-19, but probably not by itself. A combination of drugs will likely end up as the most effective therapy. This drug combo has yet to be developed, however.

Studies seem to show no difference in benefit between five-day intravenous Remdesivir treatments and ten-day treatments. This is good news because it  means all you may need is five days on the drug. That essentially doubles the global supply of the drug, while cutting the considerable cost in half.

Though the federal government has cleared the antiviral drug Remdesivir to treat some COVID-19 patients, don’t expect it to be given to everyone. The emergency use authorization by the Food and Drug Administration allows the drug to be given to patients with COVID-19 only if they are severely ill with low oxygen saturation levels that require respiratory support.

Gilead says that it will coordinate the donation of Remdesivir to hospitals in cities most heavily impacted by COVID-19. These are facilities with intensive care units the government believes most in need.

To sum up, Remdesivir isn’t a miracle drug, but it’s better than a placebo. For Remdesivir to be used more widely, it would need to meet the more rigorous standards required for permanent FDA approval.

Joe Alton MD

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