Identification

Name
Remdesivir
Accession Number
DB14761
Description

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which is a respiratory disease that is capable of progressing to viral pneumonia and acute respiratory distress syndrome (ARDS); COVID-19 can be fatal. Like other RNA viruses, SARS-CoV-2 depends on an RNA-dependent RNA polymerase (RdRp) enzyme complex for genomic replication, which can be inhibited by a class of drugs known as nucleoside analogues.10

Remdesivir (GS-5734) is an adenosine triphosphate analogue first described in the literature in 2016 as a potential treatment for Ebola.1,9 Broad antiviral activity of remdesivir is suggested by its mechanism of action,10 and to date, it has demonstrated in vitro activity against the Arenaviridae, Flaviviridae, Filoviridae, Paramyxoviridae, Pneumoviridae, and Coronaviridae viral families.9 Remdesivir activity against the Coronaviridae family was first demonstrated in 2017,2 leading to considerable interest in remdesivir as a possible treatment for COVID-19.4,8 Remdesivir was confirmed as a non-obligate chain terminator of RdRp from SARS-CoV-2 and the related SARS-CoV and MERS-CoV,10 and has been investigated in multiple COVID-19 clinical trials.12,13

Based on aggregate data, remdesivir was granted an FDA Emergency Use Authorization (EUA) on May 1st, 2020.14 The FDA subsequently granted full approval for remdesivir as a COVID-19 treatment on October 22, 2020, while simultaneously updating the EUA to cover those patients not included under the approved indication.18 Remdesivir is currently marketed under the trademark name VEKLURY® by Gilead Sciences Inc.18

Remdesivir in combination with baricitinib for the treatment of COVID-19, was granted an FDA Emergency Use Authorization on 19 Novermber 2020.19

Type
Small Molecule
Groups
Approved, 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 is indicated for the treatment of adult and pediatric patients aged 12 years and over weighing at least 40 kg for coronavirus disease 2019 (COVID-19) infection requiring hospitalization. Under this indication, remdesivir should only be administered in a hospital or other healthcare setting capable of providing acute care comparable to an inpatient hospital setting.18

Remdesivir was originally granted FDA Emergency Use Authorization (EUA)15 on May 1, 2020, for use in adults and children with suspected or confirmed COVID-19 in a hospital setting with an SpO2 ≤94%.16 Following FDA approval, this EUA was revised to cover hospitalized pediatric patients between 3.5 and 40 kg, as well as those under 12 years of age that weigh at least 3.5 kg, with suspected or laboratory-confirmed COVID-19.14

Under both the on-label and EUA indications, patients not needing invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) should be treated for 5 days (including the loading dose on day 1) and may be extended up to 10 days if they do not show improvement. Patients requiring invasive mechanical ventilation or ECMO should be treated for 10 days.16,18

Associated Conditions
Contraindications & Blackbox Warnings
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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.16 Due to much higher selectivity of mammalian DNA and RNA polymerases, including human mitochondrial RNA polymerase, for ATP over remdesivir triphosphate, remdesivir is not a significant inhibitor of these enzymes, which contributes to its overall tolerability and safety profile.10,18 Despite this, remdesivir carries risks for hypersensitivity reactions, including anaphylaxis and other infusion-related reactions, elevated transaminase levels, and potential decreased efficacy when combined with hydroxychloroquine or chloroquine.16,18

Mechanism of action

COVID-19 is caused by the positive-sense RNA virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Replication of the viral genome is a key step in the infectious cycle of RNA viruses, including those of the Filoviridae, Paramyxoviridae, Pneumoviridae, and Coronaviridae families, and is carried out by viral RNA-dependent RNA polymerase (RdRp) enzymes or enzyme complexes.9,10 For both SARS-CoV and SARS-CoV-2, the RdRp comprises nsp7, nsp8, and nsp12 subunits under physiological conditions, although functional RdRp complexes can be reassembled in vitro that incorporate only the nsp8 and nsp12 subunits, similar to the Middle East respiratory syndrome coronavirus (MERS-CoV).10

Remdesivir is a phosphoramidite prodrug of a 1'-cyano-substituted adenosine nucleotide analogue that competes with ATP for incorporation into newly synthesized viral RNA by the corresponding RdRp complex.10 Remdesivir enters cells before being cleaved to its monophosphate form through the action of either carboxylesterase 1 or cathepsin A; it is subsequently phosphorylated by undescribed kinases to yield its active triphosphate form remdesivir triphosphate (RDV-TP or GS-443902).9,18 RDV-TP is efficiently incorporated by the SARS-CoV-2 RdRp complex, with a 3.65-fold selectivity for RDV-TP over endogenous ATP.10,18 Unlike some nucleoside analogues, remdesivir provides a free 3'-hydroxyl group that allows for continued chain elongation.10,18 However, modelling and in vitro experiments suggest that at i + 4 (corresponding to the position for the incorporation of the fourth nucleotide following RDV-TP incorporation), the 1'-cyano group of remdesivir sterically clashes with Ser-861 of the RdRp, preventing further enzyme translocation and terminating replication at position i + 3. This mechanism was essentially identical between SARS-CoV, SARS-CoV-2, and MERS-CoV, and genomic comparisons reveal that Ser-861 is conserved across alpha-, beta-, and deltacoronaviruses, suggesting remdesivir may possess broad antiviral activity.10

Considerations for the use of nucleotide analogues like remdesivir include the possible accumulation of resistance mutations. Excision of analogues through the 3'-5' exonuclease (ExoN) activity of replication complexes, mediated in SARS-CoV by the nsp14 subunit, is of possible concern.10 Murine hepatitis viruses (MHVs) engineered to lack ExoN activity are approximately 4-fold more susceptible to remdesivir, supporting the proposed mechanism of action.3 However, the relatively mild benefit of ExoN activity to remdesivir resistance is proposed to involve its delayed chain termination mechanism, whereby additional endogenous nucleotides are incorporated following RDV-TP.10 In addition, serial passage of MHV in increasing concentrations of the remdesivir parent molecule GS-441524 led to the development of resistance mutations F476L and V553L, which maintain activity when transferred to SARS-CoV. However, these mutant viruses are less fit than wild-type in both competition assays and in vivo in the absence of selective pressure.3 To date, no clinical data on SARS-CoV-2 resistance to remdesivir have been described.18

TargetActionsOrganism
AReplicase polyprotein 1ab
inhibitor
SARS-CoV-2
UReplicase polyprotein 1ab
inhibitor
SARS-CoV
UReplicase polyprotein 1ab
inhibitor
Middle East respiratory syndrome-related coronavirus (isolate United Kingdom/H123990006/2012)
URNA-directed RNA polymerase L
inhibitor
Zaire ebolavirus (strain Mayinga-76)
Absorption

Remdesivir is absorbed quickly; maximal plasma concentrations following a single 30-minute intravenous infusion are reached within 0.67-0.68 hours (Tmax). Repeated dosing yields a Cmax (coefficient of variation as a percent) of 2229 (19.2) ng/mL and an AUCtau of 1585 (16.6) ng*h/mL.18

Remdesivir metabolite GS-441524 has measured values: Tmax 1.51-2.00 hours, Cmax 145 (19.3) ng/mL, AUCtau 2229 (18.4) ng*h/mL, and Ctrough 69.2 (18.2) ng/mL. Another metabolite, GS-704277, has measured values: Tmax 0.75 hours, Cmax 246 (33.9) ng/mL, AUCtau 462 (31.4) ng*h/mL, and an undetermined Ctrough.18

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

Remdesivir is 88-93.6% bound to human plasma proteins while its metabolites GS-441524 and GS-704277 are 2% and 1% bound, respectively.18

Metabolism

Remdesivir is a phosphoramidate prodrug that must be metabolized within host cells to its triphosphate metabolite to be therapeutically active.1,2,11 Upon cell entry, remdesivir is presumed to undergo first esterase-mediated hydrolysis to a carboxylate form followed by cyclization to eject the phenoxide moiety and finally hydrolysis of the cyclic anhydride to yield the detectable alanine metabolite (GS-704277).11 The alanine metabolite is subsequently hydrolyzed to yield the monophosphate form of remdesivir, which is either hydrolyzed again to yield the bare nucleoside metabolite GS-441524 or phosphorylated by cellular kinases to yield the active triphosphate form.1,11

Hover over products below to view reaction partners

Route of elimination

Remdesivir is 74% eliminated in the urine and 18% eliminated in the feces.16 49% of the recovered dose is in the form of the metabolite GS-441524, and 10% is recovered as the unmetabolized parent compound.16 A small amount (0.5%) of the GS-441524 metabolite is found in feces.18

Half-life

Remdesivir has an elimination half-life of 1 hour following a single 30-minute intravenous infusion. Under the same conditions, the elimination half-lives of the remdesivir metabolites GS-441524 and GS-704277 are 27 hours and 1.3 hours, respectively.18

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
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Toxicity

Data regarding overdoses of remdesivir are not readily available.16 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
AbametapirThe serum concentration of Remdesivir can be increased when it is combined with Abametapir.
AbemaciclibThe excretion of Abemaciclib can be decreased when combined with Remdesivir.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Remdesivir.
AcetylcysteineThe excretion of Remdesivir can be decreased when combined with Acetylcysteine.
AcyclovirThe excretion of Acyclovir can be decreased when combined with Remdesivir.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Remdesivir.
AfatinibThe serum concentration of Remdesivir can be increased when it is combined with Afatinib.
AlfuzosinThe metabolism of Alfuzosin can be decreased when combined with Remdesivir.
AlprazolamThe metabolism of Alprazolam can be decreased when combined with Remdesivir.
AmbrisentanThe serum concentration of Ambrisentan can be increased when it is combined with Remdesivir.
Additional Data Available
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  • Severity
    Severity
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  • Evidence Level
    Evidence Level
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Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
VekluryPowder, for solution100 mgIntravenousGilead SciencesNot applicableNot applicableCanada flag
VekluryInjection5 mg/1mLIntravenousGilead Sciences, Inc.2021-09-01Not applicableUS flag
VeklurySolution100 mgIntravenousGilead SciencesNot applicableNot applicableCanada flag
VekluryInjection, powder, lyophilized, for solution100 mg/1IntravenousGilead Sciences, Inc.2020-11-01Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number
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    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
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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

Synthesis Reference

Byoung Kwon Chun, Michael O'Neil Hanrahan Clarke, Edward Doerffler, Hon Chung Hui, Robert Jordan, Richard L. Mackman, Jay P. Parrish, Adrian S. Ray, and Dustin Siegel, "Methods for treating Filoviridae virus infections." U.S. Patent US9724360B2, issued August 8, 2017.

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. Malin JJ, Suarez I, Priesner V, Fatkenheuer G, Rybniker J: Remdesivir against COVID-19 and Other Viral Diseases. Clin Microbiol Rev. 2020 Oct 14;34(1). pii: 34/1/e00162-20. doi: 10.1128/CMR.00162-20. Print 2020 Dec 16. [PubMed:33055231]
  10. Gordon CJ, Tchesnokov EP, Woolner E, Perry JK, Feng JY, Porter DP, Gotte M: 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. 2020 May 15;295(20):6785-6797. doi: 10.1074/jbc.RA120.013679. Epub 2020 Apr 13. [PubMed:32284326]
  11. Eastman RT, Roth JS, Brimacombe KR, Simeonov A, Shen M, Patnaik S, Hall MD: Remdesivir: A Review of Its Discovery and Development Leading to Emergency Use Authorization for Treatment of COVID-19. ACS Cent Sci. 2020 May 27;6(5):672-683. doi: 10.1021/acscentsci.0c00489. Epub 2020 May 4. [PubMed:32483554]
  12. NIH: Clinical Trial NCT04252664 [Link]
  13. NIH: Clinical Trial NCT04257656 [Link]
  14. FDA: Emergency Use Authorization For Remdesivir [Link]
  15. FDA: Emergency Use Authorization Information [Link]
  16. FDA: Fact Sheet For Health Care Providers EUA of Remdesivir [Link]
  17. FDA Press Announcement: FDA Approves Remdesivir for COVID-19 [Link]
  18. FDA Approved Drug Products: VEKLURY (remdesivir) injection [Link]
  19. FDA: Emergency Use Authorization for Baricitinib in Combination with Remdesivir for COVID-19 [Link]
ChemSpider
58827832
RxNav
2284718
ChEBI
145994
ChEMBL
CHEMBL4065616
Wikipedia
Remdesivir

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentNovel Coronavirus Infectious Disease (COVID-19)3
3CompletedTreatmentNovel Coronavirus Infectious Disease (COVID-19)3
3Not Yet RecruitingTreatmentNovel Coronavirus Infectious Disease (COVID-19)1
3RecruitingTreatmentCOVID-19 Pneumonia / Novel Coronavirus Infectious Disease (COVID-19)1
3RecruitingTreatmentCOVID / COVID - 19 / Novel Coronavirus Infectious Disease (COVID-19) / SARS (Severe Acute Respiratory Syndrome)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
2Active Not RecruitingTreatmentNovel Coronavirus Infectious Disease (COVID-19)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionIntravenous5 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous100 mg/1
Powder, for solutionIntravenous100 mg
SolutionIntravenous100 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
logP2.01ChemAxon
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
Polarizability59.88 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-2
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
Remdesivir acts as a non-obligate chain termination inhibitor of SARS-CoV-2 viral replication through incorporation into the growing nucleotide chain in place of ATP.
General 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.
Specific Function
Atp binding
Gene Name
rep
Uniprot ID
P0DTD1
Uniprot Name
Replicase polyprotein 1ab
Molecular Weight
794051.285 Da
References
  1. Gordon CJ, Tchesnokov EP, Woolner E, Perry JK, Feng JY, Porter DP, Gotte M: 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. 2020 May 15;295(20):6785-6797. doi: 10.1074/jbc.RA120.013679. Epub 2020 Apr 13. [PubMed:32284326]
  2. FDA Approved Drug Products: VEKLURY (remdesivir) injection [Link]
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]
  2. Gordon CJ, Tchesnokov EP, Woolner E, Perry JK, Feng JY, Porter DP, Gotte M: 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. 2020 May 15;295(20):6785-6797. doi: 10.1074/jbc.RA120.013679. Epub 2020 Apr 13. [PubMed:32284326]
Kind
Protein
Organism
Middle East respiratory syndrome-related coronavirus (isolate United Kingdom/H123990006/2012)
Pharmacological action
Unknown
Actions
Inhibitor
General Function
The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products.
Specific Function
Atp binding
Gene Name
rep
Uniprot ID
K9N7C7
Uniprot Name
Replicase polyprotein 1ab
Molecular Weight
789556.615 Da
References
  1. Gordon CJ, Tchesnokov EP, Woolner E, Perry JK, Feng JY, Porter DP, Gotte M: 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. 2020 May 15;295(20):6785-6797. doi: 10.1074/jbc.RA120.013679. Epub 2020 Apr 13. [PubMed:32284326]
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
Yes
Actions
Substrate
Curator comments
Remdesivir is a prodrug that is metabolized to its active nucleoside monophosphate form within cells by the action of ccarboxyesterase 1 and/or cathepsin A.
General Function
Triglyceride lipase activity
Specific Function
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acy...
Gene Name
CES1
Uniprot ID
P23141
Uniprot Name
Liver carboxylesterase 1
Molecular Weight
62520.62 Da
References
  1. FDA Approved Drug Products: VEKLURY (remdesivir) injection [Link]
Kind
Protein
Organism
Not Available
Pharmacological action
Yes
Actions
Substrate
Curator comments
Remdesivir is a prodrug that is metabolized to its active nucleoside monophosphate form within cells by the action of ccarboxyesterase 1 and/or cathepsin A.
General Function
Protective protein appears to be essential for both the activity of beta-galactosidase and neuraminidase, it associates with these enzymes and exerts a protective function necessary for their stability and activity. This protein is also a carboxypeptidase and can deamidate tachykinins.
Specific Function
Carboxypeptidase activity
Gene Name
CTSA
Uniprot ID
P10619
Uniprot Name
Lysosomal protective protein
Molecular Weight
54465.655 Da
References
  1. FDA Approved Drug Products: VEKLURY (remdesivir) injection [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. Yang K: What Do We Know About Remdesivir Drug Interactions? Clin Transl Sci. 2020 Sep;13(5):842-844. doi: 10.1111/cts.12815. Epub 2020 Jun 26. [PubMed:32402130]
  2. FDA: Fact Sheet For Health Care Providers EUA of Remdesivir [Link]
  3. Flockhart Table of Drug Interactions [Link]
  4. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  5. FDA Approved Drug Products: VEKLURY (remdesivir) injection [Link]
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. Yang K: What Do We Know About Remdesivir Drug Interactions? Clin Transl Sci. 2020 Sep;13(5):842-844. doi: 10.1111/cts.12815. Epub 2020 Jun 26. [PubMed:32402130]
  2. FDA: Fact Sheet For Health Care Providers EUA of Remdesivir [Link]
  3. Flockhart Table of Drug Interactions [Link]
  4. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [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. Yang K: What Do We Know About Remdesivir Drug Interactions? Clin Transl Sci. 2020 Sep;13(5):842-844. doi: 10.1111/cts.12815. Epub 2020 Jun 26. [PubMed:32402130]
  2. FDA: Fact Sheet For Health Care Providers EUA of Remdesivir [Link]
  3. Flockhart Table of Drug Interactions [Link]
  4. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [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. Yang K: What Do We Know About Remdesivir Drug Interactions? Clin Transl Sci. 2020 Sep;13(5):842-844. doi: 10.1111/cts.12815. Epub 2020 Jun 26. [PubMed:32402130]
  2. FDA: Fact Sheet For Health Care Providers EUA of Remdesivir [Link]
  3. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  4. FDA Approved Drug Products: VEKLURY (remdesivir) injection [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. Yang K: What Do We Know About Remdesivir Drug Interactions? Clin Transl Sci. 2020 Sep;13(5):842-844. doi: 10.1111/cts.12815. Epub 2020 Jun 26. [PubMed:32402130]
  2. FDA: Fact Sheet For Health Care Providers EUA of Remdesivir [Link]
  3. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  4. FDA Approved Drug Products: VEKLURY (remdesivir) injection [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. Yang K: What Do We Know About Remdesivir Drug Interactions? Clin Transl Sci. 2020 Sep;13(5):842-844. doi: 10.1111/cts.12815. Epub 2020 Jun 26. [PubMed:32402130]
  2. FDA: Fact Sheet For Health Care Providers EUA of Remdesivir [Link]
  3. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  4. FDA Approved Drug Products: VEKLURY (remdesivir) injection [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Monovalent cation:proton antiporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name
SLC47A1
Uniprot ID
Q96FL8
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
References
  1. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  2. FDA Approved Drug Products: VEKLURY (remdesivir) injection [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. Yang K: What Do We Know About Remdesivir Drug Interactions? Clin Transl Sci. 2020 Sep;13(5):842-844. doi: 10.1111/cts.12815. Epub 2020 Jun 26. [PubMed:32402130]
  2. 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. Yang K: What Do We Know About Remdesivir Drug Interactions? Clin Transl Sci. 2020 Sep;13(5):842-844. doi: 10.1111/cts.12815. Epub 2020 Jun 26. [PubMed:32402130]
  2. 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. Yang K: What Do We Know About Remdesivir Drug Interactions? Clin Transl Sci. 2020 Sep;13(5):842-844. doi: 10.1111/cts.12815. Epub 2020 Jun 26. [PubMed:32402130]
  2. FDA: Fact Sheet For Health Care Providers EUA of Remdesivir [Link]

Drug created on April 23, 2019 16:25 / Updated on November 23, 2020 10:32

Pbdb medl 2