Remdesivir

  • Molecular formula: C27H35N6O8P
  • CAS# 1809249-37-3
  • Molecular mass: 602.576
  • 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
  • Synonymum: GS-5734
  • Brand name: Veklury
  • GS-441524 prodrug
  • Patent# US-2020276219-A1, CN-111093627-A, atď…
    Owner: Gilead Sciences , Inc
  • ChemSrc, PubChem

Remdesivir, sold under the brand name Veklury is a broad-spectrum antiviral medication developed by the biopharmaceutical company Gilead Sciences. Remdesivir is a prodrug that is intended to allow intracellular delivery of GS-441524 monophosphate and subsequent biotransformation into GS-441524 triphosphate, a ribonucleotide analogue inhibitor of viral RNA polymerase.

Mechanism of action

Remdesivir mode of action

Remdesivir specifically inhibits the activity of the viral RNA-dependent RNA-polymerase (RdRp), essential in viral replication [3-5]Upon entry into the cell, Remdesivir is rapidly metabolized into a nucleoside monophosphate (GS-441542 MP), which is then further processed into an active triphosphate form (GS-441524). GS-441524 is an adenosine triphosphate (ATP) analog and is thus, able to be used as a substrate by viral RdRp. GS-441524 outcompetes ATP for incorporation into the newly synthesized RNA strand, ultimately causing premature termination of the RNA product. However, unlike classic chain-terminators, the incorporation of GS-441524 causes delayed chain-termination downstream of this site [3, 4]. Importantly, it has been established that GS-441524 evades proofreading by the viral exoribonuclease (ExoN) [5].

Using Remdesivir for FIP treatment

Remdesivir from Bova Company - Concentration 10mg/ml

Pre legálne veterinárne použitie vyrába remdesivir spoločnosť Bova at a concentration of 10mg/ml in 10ml vials.

For severe cases of FIP, intravenous administration is also possible at the beginning of treatment.

FIP treatment success rate is about 85-90%.

Wet/Dry FIPOcular FIPNeurological FIP
7-8 mg/kg10 mg/kg12-15 mg/kg
Remdesivir dosage in the treatment of FIP according to experiences from Australia and the UK

References

  1. Warren, T.K. et al. 2016. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature 531, 381-385.
  2. Gordon, C.J. et al. 2020. The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus. J Biol Chem
  3. Gordon, C.J. et al. 2020. Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency. J Biol Chem 295, 6785-6797.
  4. Tchesnokov, E.P. et al. 2019. Mechanism of Inhibition of Ebola Virus RNA-Dependent RNA Polymerase by Remdesivir. Viruses 11
  5. Agostini, M.L. et al. 2018. Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease. mBio 9
  6. Remdesivir on Wiki
  7. Treatment of FIP in cats with Remdesivir