The global COVID-19 pandemic is currently underway. To date, there are about 1.49 million dead and 64.5 million people infected. In this period of global pandemic, several pharmacological treatments have been investigated. A good hope to fight COVID-19 comes from the excellent results derived from the latest stages of clinical trials of effective vaccines. However, even when vaccines are available, there will always be a need to continue clinical trials and research to identify effective therapies against SARS-cov-2. Among all the antiviral drugs used against SARS-cov-2, Remdesivir is currently the subject of scientific debate. Remdesivir is a carboxylic ester resulting from the formal condensation of the carboxy group of N-[(S)-{[(2R,3S,4R,5R)-5-(4-aminopyrrole[2,1-f][1,2,4]triazin-7-yl)-5-cyano- 3,4-dihydroxy tetrahydrofuran-2-yl]methoxy}(phenoxy)phosphoryl]-L-alanine with the hydroxy group of 2-ethylbutan- 1-ol. It is a prodrug of an adenosine triphosphate (ATP) analog. It is intended to allow intracellular delivery of GS- 441524 (a nucleoside analogue antiviral drug which was developed by Gilead Sciences) monophosphate and subsequent biotransformation into GS-441524 triphosphate, a ribonucleotide analogue inhibitor of viral RNA polymerase. The original use of Remdesivir was to treat hepatitis C, and was subsequently investigated for Ebola virus disease and Marburg virus infections before being studied as a post-infection treatment for COVID-19.

Those who support use of Remdesivir believe it is a life saver for Covid-19 patients while others oppose the “rampant use” of the drug. During the first wave of the pandemic, Remdesivir was approved or authorized for emergency use, to treat Covid-19 in around 50 countries. In India, the Drug Controller General of India (DCGI) has approved only emergency use of this injection. Remdesivir is a broad-spectrum antiviral medication which is administered via injection into a vein. Covid-19 patients suffering from mild to severe disease have benefitted from Remdesivir in the first five days. But if the patient is getting serious even after that, the treating doctor can continue the dose for a maximum of 10 days. However, this injection should be used with caution in patients with kidney disease.

Recently, its role in reducing mortality from COVID-19 seems to be questioned. Also considering the recent guidelines developed by the World Health Organization, there is conflicting evidence that a treatment cycle of 5 or 10 days leads to clinical improvement or not. The World Health Organization’s Solidarity study, a huge international study involving thousands of patients, has published provisional results showing that the drug does not have a significant impact on mortality or other important outcomes for patients, such as the need for mechanical ventilation or the time needed for clinical improvement. However, some studies, as also reported in other articles, associate remdesivir treatment in COVID-19 patients with continuous and clinically significant improvements in positive patients, leading to reduced mortality and reduced recovery time. Certainly, therapeutic treatment with remdesivir in COVID-19 patients requires additional data from well-structured clinical trials. However, it could be considered that the inconsistency of data from some studies is probably due to the specific and subjective immunopathology characteristic of each COVID-19 patients. In addition, if the drug treatment with remdesivir does not bring benefits, it's use could still increase the risks of possible adverse reactions; in fact, the information prescribed by the FDA for remdesivir currently includes caution notes on the need to monitor renal and liver function in human patients.

Ultimately, what is the current role of remdesivir in the treatment of COVID-19 infection? Some trials have demonstrated its antiviral efficacy in SARS-cov-2 and faster recovery; others associate lack of efficacy and increased unnecessary risks associated with treatment. Currently, research is focusing on moderately ill patients who could benefit from the drug if administered early. In conclusion, the lack of benefits in the solidarity study only reinforces the need to better understand the role and effects of remdesivir on the SARS-cov-2 virus.

Suraiyya Masuldar

T. Y. B. Pharm

Tags: MET Institute of Pharmacy