Neucrad Health April 20, 2020
Recently, a Chicago-based medical institution conducting clinical trials on COVID-19 patients with Gilead Sciences’ antiviral Remdesivir drug reported that patients responded positively after the administration of this medicine. They had a swift recovery from fever and respiratory symptoms, and most of the COVID positive patients got discharged from the hospital within a week of the onset of the symptoms.
Why were the scientist community waiting eagerly for the outcome of Gilead’s clinical trials on Remdesivir?
If you remember, Remdesivir was one of the initial medicines recommended in the treatment for coronavirus. It is the reason, scientist community across the globe was waiting patiently for results from Gilead’s clinical trials. Recently, the University of Chicago Medicine conducted a clinical trial on this medicine with a sample size of 125 candidates. Out of them, 113 patients had severe COVID-19 symptoms. However, most of them revived after the administration of Remdesivir. Now, since they have registered a positive outcome on COVID-19 patients, we may be hopeful about it. But ultimately, we will wait to hear from drug administration and other regulatory bodies whether this drug is safe and effective in curing SARS-CoV-2 infection.
What is Remdesivir?
Remdesivir is an antiviral medication produced by a reputed pharmaceutical company in the United States- Gilead Sciences. It bears a development code- GS-5734, and chemical formula- C27H35N6O8P. It consists of a nucleotide analogue (adenosine analogue), which incorporates itself within the viral RNA chains and leads to the premature death of the pathogens. Before, the onset of COVID-19 pandemic, scientists used Remdesivir in vitro and in vivo activity on animal models. According to the limited preclinical studies conducted by various research groups, it also worked efficiently against MERS and SARS coronavirus (viruses similar in structure to SARS-CoV-2).
What is the mechanism of action of Remdesivir?
Earlier research on Remdesivir indicated that the medicine blocks the replication processes of various categories of coronavirus (MERS and SARS). However, scientists were not sure about the mode of action of this drug. The study conducted by the University of Alberta and Gilead Sciences established that Remdesivir blocks a specific enzyme of the virus, crucial for its replication. Coronaviruses utilise the RNA-dependent RNA polymerase enzyme for replicating within the host body. However, it was challenging for the research team to isolate the polymerase complex and analyse it in the laboratory. It was a major block for further research in this sector .
Recent studies established that Remdesivir (a prodrug) transforms into an active form GS-441524. It acts as an adenosine nucleotide analogue and obstructs the pathway of viral RNA-dependent RNA polymerase. The drug also goes unnoticed during the proofreading by viral exoribonuclease (ExoN). Finally, the replication process of coronaviruses gets arrested [4,5].
How Pharmaceutical Companies synthesise Remdesivir?
Chemists can produce Remdesivir through multiple steps, where ribose derivatives act as the initial compound. The Gilead Sciences laboratory, follow the synthesis method invented by the famous scientist, Byoung Kwon Chun and his team. Here L-alanine and phenyl phosphorodichloridate helps in the production of an intermediate ‘a’ in the presence of triethylamine and dichloromethane. After this, dimethyl sulfoxide, along with acetic anhydride, performs the oxidation of triple benzyl-protected ribose and produce lactone intermediate ‘b’. In the same time, scientists create an intermediate ‘c’ by conducting a halogen-lithium exchange reaction of n-Butyllithium. Then intermediate ‘b’ and ‘c’ reacts to produce a 1: 1 anomer. After this, chemists produce nitrile intermediate and a benzyl-free intermediate. They also conduct an HPLC (High-performance liquid chromatography) to separate the isomers. Finally, the intermediate ‘a’ and the optically pure compound along with trimethyl phosphate and methylimidazole produce a crude Remdesivir. It undergoes chiral resolution to generate pure Remdesivir.
World is waiting for a safe and effective drug against COVID-19. In clinical trials, the drug is performing efficiently in arresting the symptoms of COVID-19 and promoting quick recovery among patients. Let’s wait to hear from regulatory agencies.