Identification

Name
Remdesivir
Accession Number
DB14761
Description

Remdesivir, or GS-5734, is an adenosine triphosphate analog first described in the literature in 2016 as a potential treatment for Ebola.1 In 2017, its activity against the coronavirus family of viruses was also demonstrated.2 Remdesivir is also being researched as a potential treatment to SARS-CoV-2, the coronavirus responsible for COVID-19.4,8

Remdesivir was granted an FDA Emergency Use Authorization on 1 May 2020.11 This is not the same as an FDA approval.12

Type
Small Molecule
Groups
Investigational
Structure
Thumb
Weight
Average: 602.585
Monoisotopic: 602.225399109
Chemical Formula
C27H35N6O8P
Synonyms
  • Remdesivir
  • Remdésivir
  • Remdesivirum
External IDs
  • GS 5734
  • GS-5734

Pharmacology

Indication

Remdesivir has an FDA Emergency Use Authorization for use in adults and children with suspected or confirmed COVID-19 in hospital with an SpO2 ≤94%.13 This is not the same as an FDA approval.12

The FDA Emergency Use Authorization suggests a loading dose of 200mg once daily in patients ≥ 40 kg or 5 mg/kg once daily in patients 3.5 kg to less than 40 kg, followed by a maintenance dose of 100mg once daily in patients ≥ 40 kg or 2.5 mg/kg once daily in patients 3.5 kg to less than 40 kg.13 Patients not needing invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) should be treated for 5 days (including the loading dose on day 1), up to 10 days if they do not show improvement.13 Patients requiring invasive mechanical ventilation or ECMO should be treated for 10 days.13

Clinical trials used a regimen of 200mg once daily on the first day, followed by 100mg once daily for another 9 days.6,9,10 Early data suggests that some patients may benefit from only 5 days of treatment.8

Remdesivir was originally investigated as a treatment for Ebola virus, but has potential to treat a variety of RNA viruses.1 Its activity against the coronavirus (CoV) family of viruses, such as SARS-CoV and MERS-CoV, was described in 2017,2 and it is also being investigated as a potential treatment for SARS-CoV-2 infections.4,7

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Remdesivir is a nucleoside analog used to inhibit the action of RNA polymerase.3 The duration of action is moderate, as it is given once daily.13 Patients should be counselled regarding the risk of infusion related reactions, elevated transaminases, and potential decreased efficacy when combined with hydroxychloroquine or chloroquine.13

Mechanism of action

Remdesivir is a nucleoside analog that is expected to inhibit the action of RNA polymerase.3 By incorporating into RNA, additional nucleotides cannot be added, terminating RNA transcription.3 Viruses with mutations in RNA polymerase to develop partial resistance to remdesivir have been shown to be less infective.3

TargetActionsOrganism
UReplicase polyprotein 1ab
inhibitor
SARS-CoV
URNA-directed RNA polymerase L
inhibitor
Zaire ebolavirus (strain Mayinga-76)
Absorption

A 10mg/kg intravenous dose given to cynomolgus monkeys distributes to the testes, epididymis, eyes, and brain within 4h.1

Volume of distribution

Data regarding the volume of distribution of remdesivir is not readily available.

Protein binding

Data regarding the protein binding of remdesivir is not readily available.

Metabolism

Remdesivir is predominantly metabolized to a triphosphate metabolite.1,2

Hover over products below to view reaction partners

Route of elimination

Remdesivir is 74% eliminated in the urine and 18% eliminated in the feces.13 49% of the recovered dose is in the form of the metabolite GS-441524, and 10% is recovered as the unmetabolized parent compound.13

Half-life

A 10mg/kg intravenous dose in non human primates has a plasma half life of 0.39h.1 The nucleoside triphosphate metabolite has a half life of 14h in non human primates.1 The nucleoside triphosphate metabolite has a half life of approximately 20 hours in humans.2

Clearance

Data regarding the clearance of remdesivir is not readily available.

Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

Data regarding overdoses of remdesivir are not readily available.13 Overdoses of other nucleoside analogs like acyclovir can be managed with symptomatic and supportive treatment.5

Affected organisms
  • SARS-CoV
  • SARS-CoV-2
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
ChloroquineThe therapeutic efficacy of Remdesivir can be decreased when used in combination with Chloroquine.
HydroxychloroquineThe therapeutic efficacy of Remdesivir can be decreased when used in combination with Hydroxychloroquine.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
No interactions found.

Products

Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
RemdesivirInjection, powder, lyophilized, for solution100 mg/1IntravenousGilead Sciences, Inc.2020-05-01Not applicableUS flag
RemdesivirInjection5 mg/1mLIntravenousGilead Sciences, Inc.2020-05-01Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
RemdesivirRemdesivir (100 mg/1)Injection, powder, lyophilized, for solutionIntravenousGilead Sciences, Inc.2020-05-01Not applicableUS flag
RemdesivirRemdesivir (5 mg/1mL)InjectionIntravenousGilead Sciences, Inc.2020-05-01Not applicableUS flag

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as alpha amino acid esters. These are ester derivatives of alpha amino acids.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Alpha amino acid esters
Alternative Parents
C-glycosyl compounds / Alanine and derivatives / Pentoses / Pyrrolo[2,1-f][1,2,4]triazines / Phosphoric diester monoamides / Phenoxy compounds / Substituted pyrroles / Organic phosphoramides / Imidolactams / 1,2,4-triazines
show 15 more
Substituents
1,2,4-triazine / 1,2-diol / Alanine or derivatives / Alcohol / Alpha-amino acid ester / Amine / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / C-glycosyl compound
show 34 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Chemical Identifiers

UNII
3QKI37EEHE
CAS number
1809249-37-3
InChI Key
RWWYLEGWBNMMLJ-YSOARWBDSA-N
InChI
InChI=1S/C27H35N6O8P/c1-4-18(5-2)13-38-26(36)17(3)32-42(37,41-19-9-7-6-8-10-19)39-14-21-23(34)24(35)27(15-28,40-21)22-12-11-20-25(29)30-16-31-33(20)22/h6-12,16-18,21,23-24,34-35H,4-5,13-14H2,1-3H3,(H,32,37)(H2,29,30,31)/t17-,21+,23+,24+,27-,42-/m0/s1
IUPAC Name
2-ethylbutyl (2S)-2-{[(S)-{[(2R,3S,4R,5R)-5-{4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl}-5-cyano-3,4-dihydroxyoxolan-2-yl]methoxy}(phenoxy)phosphoryl]amino}propanoate
SMILES
CCC(CC)COC(=O)[[email protected]](C)N[[email protected]](=O)(OC[[email protected]]1O[[email protected]](C#N)([[email protected]](O)[[email protected]@H]1O)C1=CC=C2N1N=CN=C2N)OC1=CC=CC=C1

References

General References
  1. Warren TK, Jordan R, Lo MK, Ray AS, Mackman RL, Soloveva V, Siegel D, Perron M, Bannister R, Hui HC, Larson N, Strickley R, Wells J, Stuthman KS, Van Tongeren SA, Garza NL, Donnelly G, Shurtleff AC, Retterer CJ, Gharaibeh D, Zamani R, Kenny T, Eaton BP, Grimes E, Welch LS, Gomba L, Wilhelmsen CL, Nichols DK, Nuss JE, Nagle ER, Kugelman JR, Palacios G, Doerffler E, Neville S, Carra E, Clarke MO, Zhang L, Lew W, Ross B, Wang Q, Chun K, Wolfe L, Babusis D, Park Y, Stray KM, Trancheva I, Feng JY, Barauskas O, Xu Y, Wong P, Braun MR, Flint M, McMullan LK, Chen SS, Fearns R, Swaminathan S, Mayers DL, Spiropoulou CF, Lee WA, Nichol ST, Cihlar T, Bavari S: Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature. 2016 Mar 17;531(7594):381-5. doi: 10.1038/nature17180. Epub 2016 Mar 2. [PubMed:26934220]
  2. Sheahan TP, Sims AC, Graham RL, Menachery VD, Gralinski LE, Case JB, Leist SR, Pyrc K, Feng JY, Trantcheva I, Bannister R, Park Y, Babusis D, Clarke MO, Mackman RL, Spahn JE, Palmiotti CA, Siegel D, Ray AS, Cihlar T, Jordan R, Denison MR, Baric RS: Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med. 2017 Jun 28;9(396). pii: 9/396/eaal3653. doi: 10.1126/scitranslmed.aal3653. [PubMed:28659436]
  3. Agostini ML, Andres EL, Sims AC, Graham RL, Sheahan TP, Lu X, Smith EC, Case JB, Feng JY, Jordan R, Ray AS, Cihlar T, Siegel D, Mackman RL, Clarke MO, Baric RS, Denison MR: Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease. mBio. 2018 Mar 6;9(2). pii: mBio.00221-18. doi: 10.1128/mBio.00221-18. [PubMed:29511076]
  4. de Wit E, Feldmann F, Cronin J, Jordan R, Okumura A, Thomas T, Scott D, Cihlar T, Feldmann H: Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection. Proc Natl Acad Sci U S A. 2020 Feb 13. pii: 1922083117. doi: 10.1073/pnas.1922083117. [PubMed:32054787]
  5. Vander T, Medvedovsky M, Herishanu Y: Encephalopathy induced by oral acyclovir in a patient with normal renal function. J Infect. 2003 May;46(4):286. doi: 10.1053/jinf.2002.1119. [PubMed:12799156]
  6. Ko WC, Rolain JM, Lee NY, Chen PL, Huang CT, Lee PI, Hsueh PR: Arguments in favor of remdesivir for treating SARS-CoV-2 infections. Int J Antimicrob Agents. 2020 Mar 5:105933. doi: 10.1016/j.ijantimicag.2020.105933. [PubMed:32147516]
  7. Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A, Feldt T, Green G, Green ML, Lescure FX, Nicastri E, Oda R, Yo K, Quiros-Roldan E, Studemeister A, Redinski J, Ahmed S, Bernett J, Chelliah D, Chen D, Chihara S, Cohen SH, Cunningham J, D'Arminio Monforte A, Ismail S, Kato H, Lapadula G, L'Her E, Maeno T, Majumder S, Massari M, Mora-Rillo M, Mutoh Y, Nguyen D, Verweij E, Zoufaly A, Osinusi AO, DeZure A, Zhao Y, Zhong L, Chokkalingam A, Elboudwarej E, Telep L, Timbs L, Henne I, Sellers S, Cao H, Tan SK, Winterbourne L, Desai P, Mera R, Gaggar A, Myers RP, Brainard DM, Childs R, Flanigan T: Compassionate Use of Remdesivir for Patients with Severe Covid-19. N Engl J Med. 2020 Apr 10. doi: 10.1056/NEJMoa2007016. [PubMed:32275812]
  8. Ledford H: Hopes rise on coronavirus drug remdesivir. Nature. 2020 Apr 29. pii: 10.1038/d41586-020-01295-8. doi: 10.1038/d41586-020-01295-8. [PubMed:32350436]
  9. NIH: Clinical Trial NCT04252664 [Link]
  10. NIH: Clinical Trial NCT04257656 [Link]
  11. FDA: Emergency Use Authorization For Remdesivir [Link]
  12. FDA: Emergency Use Authorization Information [Link]
  13. FDA: Fact Sheet For Health Care Providers EUA of Remdesivir [Link]
ChemSpider
58827832
RxNav
2284718
ChEBI
145994
ChEMBL
CHEMBL4065616
Wikipedia
Remdesivir

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentNovel Coronavirus Infectious Disease (COVID-19)1
3CompletedTreatmentNovel Coronavirus Infectious Disease (COVID-19)3
3Not Yet RecruitingTreatmentCOVID / COVID - 19 / Novel Coronavirus Infectious Disease (COVID-19) / SARS (Severe Acute Respiratory Syndrome)1
3RecruitingTreatmentCOVID-19 Pneumonia / Novel Coronavirus Infectious Disease (COVID-19)1
3RecruitingTreatmentInfections, Coronavirus / Novel Coronavirus Infectious Disease (COVID-19)1
3RecruitingTreatmentNovel Coronavirus Infectious Disease (COVID-19)3
3SuspendedTreatmentNovel Coronavirus Infectious Disease (COVID-19)1
3TerminatedTreatmentNovel Coronavirus Infectious Disease (COVID-19) / Remdesivir1
2CompletedTreatmentEbola1
2Not Yet RecruitingBasic ScienceEbola / Human Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionIntravenous5 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous100 mg/1
Powder, for solutionIntravenous
SolutionIntravenous
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.339 mg/mLALOGPS
logP2.2ALOGPS
logP2.01ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)10.23ChemAxon
pKa (Strongest Basic)0.65ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area203.55 Å2ChemAxon
Rotatable Bond Count14ChemAxon
Refractivity161.81 m3·mol-1ChemAxon
Polarizability59.72 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

Kind
Protein
Organism
SARS-CoV
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Replicase polyprotein 1ab: Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein.Host transl...
Gene Name
rep
Uniprot ID
P0C6X7
Uniprot Name
Replicase polyprotein 1ab
Molecular Weight
790241.63 Da
References
  1. Agostini ML, Andres EL, Sims AC, Graham RL, Sheahan TP, Lu X, Smith EC, Case JB, Feng JY, Jordan R, Ray AS, Cihlar T, Siegel D, Mackman RL, Clarke MO, Baric RS, Denison MR: Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease. mBio. 2018 Mar 6;9(2). pii: mBio.00221-18. doi: 10.1128/mBio.00221-18. [PubMed:29511076]
Kind
Protein
Organism
Zaire ebolavirus (strain Mayinga-76)
Pharmacological action
Unknown
Actions
Inhibitor
General Function
RNA-directed RNA polymerase that catalyzes the transcription of viral mRNAs, their capping and polyadenylation. The template is composed of the viral RNA tightly encapsidated by the nucleoprotein (N). The viral polymerase binds to the genomic RNA at the 3' leader promoter, and transcribes subsequently all viral mRNAs with a decreasing efficiency. The first gene is the most transcribed, and the last the least transcribed. The viral phosphoprotein acts as a processivity factor. Capping is concommitant with initiation of mRNA transcription. Indeed, a GDP polyribonucleotidyl transferase (PRNTase) adds the cap structure when the nascent RNA chain length has reached few nucleotides. Ribose 2'-O methylation of viral mRNA cap precedes and facilitates subsequent guanine-N-7 methylation, both activities being carried by the viral polymerase. Polyadenylation of mRNAs occur by a stuttering mechanism at a slipery stop site present at the end viral genes. After finishing transcription of a mRNA, the polymerase can resume transcription of the downstream gene.
Specific Function
Atp binding
Gene Name
L
Uniprot ID
Q05318
Uniprot Name
RNA-directed RNA polymerase L
Molecular Weight
252722.045 Da
References
  1. Tchesnokov EP, Feng JY, Porter DP, Gotte M: Mechanism of Inhibition of Ebola Virus RNA-Dependent RNA Polymerase by Remdesivir. Viruses. 2019 Apr 4;11(4). pii: v11040326. doi: 10.3390/v11040326. [PubMed:30987343]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. FDA: Fact Sheet For Health Care Providers EUA of Remdesivir [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. FDA: Fact Sheet For Health Care Providers EUA of Remdesivir [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. FDA: Fact Sheet For Health Care Providers EUA of Remdesivir [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. FDA: Fact Sheet For Health Care Providers EUA of Remdesivir [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. FDA: Fact Sheet For Health Care Providers EUA of Remdesivir [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. FDA: Fact Sheet For Health Care Providers EUA of Remdesivir [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. FDA: Fact Sheet For Health Care Providers EUA of Remdesivir [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Atpase activity, coupled to transmembrane movement of substances
Specific Function
May be an organic anion pump relevant to cellular detoxification.
Gene Name
ABCC4
Uniprot ID
O15439
Uniprot Name
Multidrug resistance-associated protein 4
Molecular Weight
149525.33 Da
References
  1. FDA: Fact Sheet For Health Care Providers EUA of Remdesivir [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Virus receptor activity
Specific Function
The hepatic sodium/bile acid uptake system exhibits broad substrate specificity and transports various non-bile acid organic compounds as well. It is strictly dependent on the extracellular presenc...
Gene Name
SLC10A1
Uniprot ID
Q14973
Uniprot Name
Sodium/bile acid cotransporter
Molecular Weight
38118.64 Da
References
  1. FDA: Fact Sheet For Health Care Providers EUA of Remdesivir [Link]

Drug created on April 23, 2019 16:25 / Updated on June 16, 2020 21:21

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