Mechanism of Action of Remdesivir (Veklury)

Introduction

Remdesivir is an intravenous antiviral prodrug that inhibits viral RNA-dependent RNA polymerase (RdRp). Originally developed for Ebola, it is approved for COVID-19 in hospitalized and non-hospitalized high-risk patients. It also shows activity against several RNA viruses.

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Step-by-Step Mechanism of Action

1. Cellular uptake and metabolism
   Remdesivir enters infected host cells and is metabolized to its active triphosphate form.
2. Competitive incorporation into viral RNA
   The active nucleoside analog competes with ATP as a substrate for viral RdRp.
3. Chain termination
   Once incorporated, it causes delayed RNA chain termination, halting viral replication after adding a few more nucleotides.
4. Inhibition of viral replication
   Blocked RNA synthesis reduces production of viral progeny, limiting infection spread within the host.
5. Increased viral clearance
   Reduced viral load supports recovery and improved clinical outcomes.

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Pharmacokinetic Parameters

Parameter	Value
Route	Intravenous infusion (single or multiple doses)
Distribution	Extensive tissue uptake, including lungs
Half-life (parent)	~1 hour
Half-life (metabolite)	~20–25 hours
Metabolism	Intracellular conversion to active triphosphate
Excretion	Renal (~74%) and fecal (~18%) metabolites

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Clinical Uses

• Treatment of hospitalized patients with COVID-19
• Use in non-hospitalized high-risk patients with mild-to-moderate COVID-19
• Investigational use in other RNA viral infections under study

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Adverse Effects

• Infusion-related reactions: nausea, hypersensitivity
• Elevated liver enzymes
• Rare kidney tubular toxicity (use with caution in renal impairment)
• Possible effects on kidney function in patients with low GFR

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Comparative Analysis

Drug	Mechanism	Route	Indication
Remdesivir	RdRp inhibitor; delayed chain termination	IV infusion	COVID-19
Molnupiravir	Promotes viral RNA mutagenesis	Oral tablet	Mild-to-moderate COVID-19
Paxlovid (nirmatrelvir/ritonavir)	Protease inhibitor	Oral tablet	Early COVID-19

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MCQs

1. Remdesivir is a prodrug that targets:
   a) Viral protease b) RNA-dependent RNA polymerase c) Spike protein d) Viral helicase
   Answer: b) RNA-dependent RNA polymerase
2. Its active form is a:
   a) Monophosphate b) Diphosphate c) Triphosphate d) Nucleoside
   Answer: c) Triphosphate
3. It terminates viral RNA strand by:
   a) Immediate termination b) Delayed termination c) Proteolytic cleavage d) Methylation
   Answer: b) Delayed termination
4. Route of administration is:
   a) Oral b) IV infusion c) Subcutaneous d) Intramuscular
   Answer: b) IV infusion
5. Which is a significant adverse effect?
   a) QT prolongation b) Elevated liver enzymes c) Hypoglycemia d) Hypertension
   Answer: b) Elevated liver enzymes
6. Which antiviral is taken orally for COVID-19?
   a) Remdesivir b) Molnupiravir c) Veklury d) Ribavirin
   Answer: b) Molnupiravir
7. The main elimination route is:
   a) Pulmonary excretion b) Renal metabolites c) Bile d) Sweat
   Answer: b) Renal metabolites
8. Remdesivir primarily helps by:
   a) Blocking entry of virus b) Preventing viral RNA synthesis c) Neutralizing spike protein d) Activating host cell apoptosis
   Answer: b) Preventing viral RNA synthesis
9. Its half-life in circulation is approximately:
   a) 5 minutes b) 1 hour c) 6 hours d) 24 hours
   Answer: b) 1 hour
10. A key cellular process required is:
    a) Hepatic biotransformation b) Intracellular phosphorylation c) Direct proteolysis d) HDL-binding
    Answer: b) Intracellular phosphorylation

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FAQs

1. Is remdesivir safe in renal impairment?
Use with caution in patients with GFR <30; monitor renal function.

2. When should it be administered for best results?
Early in disease—ideally within 7–10 days of symptom onset.

3. Does remdesivir shorten hospital stay?
Yes—clinical trials show faster recovery in hospitalized patients.

4. Is combination therapy used?
Often used with dexamethasone or other immunomodulators in severe cases.

5. Can it be used in other viral infections?
Research is ongoing for viruses like RSV, Ebola variants, and others.

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References

• FDA Label: Remdesivir (Veklury)
• PubMed Review: Remdesivir antiviral mechanism
• DrugBank: Remdesivir Detailed Summary
• StatPearls: Remdesivir in COVID-19
• PubMed Central: RNA polymerase inhibition data