Remdesivir, or GS-5734, is a broad-spectrum antiviral drug, which is an adenosine triphosphate analog and was first developed by the American biopharmaceutical company, Gilead Sciences (headquartered in Foster City, California) in 2014 as a possible treatment for Ebola Hemorrhagic Virus (EBV) and Marburg Virus infection, but it didn’t work against them.
The drug was developed by a team of scientists led by Czech scientist Tomáš Cihlář who is a biochemist at Gilead Sciences.
Czech Scientist Tomáš Cihlář
In 2017, it was demonstrated that the drug also worked against the coronavirus family, including Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome MERS); however, it has not been approved for these viral infections. Amid the Corona pandemic, Remdesivir made headlines for being one of the most effective prophylaxis drugs against COVID-19 but evidence on effectiveness is mixed. Remdesivir is, in fact, an experimental antiviral drug, which has been approved by the United States Food and Drug Administration (US FDA) for “emergency use authorization” in the US.
Formula
C27H35N6O8P
The IUPAC name of Remdesivir is – 2-ethylbutyl (2S)-2-[[[(2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxyoxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate.
Uses
Remdesivir is intravenous which means it is administered by injection into a vein. Various studies suggest that Remdesivir works against single-stranded RNA viruses. Being an experimental antiviral drug, the specific uses of Remdesiver is yet to be established after clinical trials. Although Gilead Sciences claim that Remdesivir has antiviral activity in vitro against multiple filoviruses, pneumoviruses, paramyxoviruses, and coronaviruses, in vivo studies have not given sufficient data against its effectiveness.
The most effective study which claims that Remdesivir can be a potential drug against COVID-19 is based on its in vivo activity in animal models against the viral pathogens that cause SARS and MERS, which are coronaviruses structurally similar to SARS-CoV-2, the coronavirus that causes COVID-19. As prophylaxis, Remdesivir has been used in the following cases:
1. Ebola Virus
During the West African Ebola Virus epidemic (2014-16), Remdesivir was designed for the treatment of the Ebola Hemorrhagic Virus (EBV).
Ebola Virus Life Cycle
Its clinical trials were carried out under the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) and Gilead Sciences. The preclinical results of Remdesivir revealed that it had blocked the Ebola virus in Rhesus monkey. After the “initial screening” of Remdesivir by scientists at the Centers for Disease Control and Prevention (CDC), it was recommended that the drug “should be further developed as a potential treatment.” After extensive clinical trials during the West African Ebola Virus epidemic (2014-16), promising preliminary results were found until August 2019, when it was found that Remdesivir was less effective than monoclonal antibody treatments, such as mAb114 and REGN-EB3.
2. COVID-19
Amid all the possible treatments for COVID-19, Remdesivir is viewed as the most promising drug to halt the progression of the infection, and it has been included in the International Solidarity trial and European Discovery trial.
After Gilead Sciences started testing of Remdesivir against SARS-CoV-2 in January 2020, it claimed that the drug is effective against SARS and MERS in animal models. Thereafter, on 21 January 2020, China’s Wuhan Institute of Virology applied for a Chinese “use patent” for using Remdesivir against COVID-19; however, the Chinese trial showed that the drug was not effective against COVID-19. In March 2020, Remdesivir showed promising results in preventing the progression of the infection in rhesus macaque monkeys with COVID‑19. On 18 March 2020, the World Health Organization approved the trial of Remdesivir against COVID-19 and on 20 March 2020, the Cleveland, Ohio-based University Hospitals stated they would run two clinical trials to test the effectiveness of Remdesivir against COVID-19.
Since there is no effective and safe medicine against COVID-19, the FDA has authorized the emergency use of Remdesivir for the treatment of patients with COVID-19 under an Emergency Use Authorization (EUA).
3. Use for Other Animals
In late 2019, Remdesivir showed promising results in cats for the treatment of coronavirus infection called feline infectious peritonitis. Although the FDA has not approved its efficacy, the drug has been available in black markets since 2019.
Remdesivir and Feline Infectious Peritonitis
Side Effects
Since Remdesivir is an investigational antiviral medicine, not all the possible side effects of it are available. Let’s discuss some of its possible side effects:
1. Infusion-related Reactions
Some infusion-related reactions have been noted while administering Remdesivir, such as nausea, vomiting, low blood pressure, sweating, and shivering.
Infusion-related Reactions
2. Elevated Liver Enzymes
In the patients administered with Remdesivir, it has been found that it increases the level of the liver enzyme “transaminase,” which may lead to inflammation or damage to liver cells.
3. Respiratory Failure
In some cases, it has been seen that the patients receiving Remdesivir have shown respiratory failure; because of abnormal levels of oxygen and carbon dioxide in the blood. The exact mechanism through which it affects the respiratory system is still not clear.
4. Abnormality in Blood Biomarkers
The intravenous administration of Remdesivir in some patients has shown abnormality in blood biomarkers, including low potassium, low albumin, low count of platelets, and low count of red blood cells.
5. Skin-related Reactions
In some patients, the reports of skin-related reactions have also been surfaced, especially icterus (yellow discoloration of the skin).
6. Other Reactions
Apart from the above-mentioned side-effects of Remdesivir, there are some other reported side-effects of Remdesivir, including gastrointestinal distress.