Galidesivir

Identification

Name
Galidesivir
Accession Number
DB11676
Description

Galidesivir is an adenosine analogue that has been investigated for use against Zaire Ebolavirus.1 In animal studies, galidesivir was effective in increasing the survival rates from infections caused by various pathogens, including Ebola, Marburg, Yellow Fever and Zika viruses.6 In vitro, it displayed broad-spectrum antiviral activity against various negative- and positive-sense RNA viruses,2 including coronaviruses, filoviruses, and arenaviruses.4,6 Phase 1 clinical trials have begun to determine the safety of this drug in humans.5 Because of its activity against other coronaviruses, it may be studied as a potential therapy for COVID-19.

Type
Small Molecule
Groups
Investigational
Structure
Thumb
Weight
Average: 265.2685
Monoisotopic: 265.117489371
Chemical Formula
C11H15N5O3
Synonyms
  • Galidesivir
  • Galidésivir
  • Galidesivirum
  • Immucillin A
  • Immucillin-A
External IDs
  • BCX-4430
  • BCX4430

Pharmacology

Indication
Not Available
Contraindications & Blackbox Warnings
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Pharmacodynamics

Galidesivir is an adenosine analogue with a broad-spectrum antiviral activity against RNA viruses, including flaviviruses, togaviruses, bunyaviruses, arenaviruses, paramyxoviruses, coronaviruses, filoviruses, orthomyxoviruses, and picornaviruses.3

Mechanism of action

Galidesivir works by binding to viral RNA polymerase where the natural nucleotide would bind, leading to the structural change in the viral enzyme due to altered electrostatic interactions. Disruption of viral RNA polymerase activity results in premature termination of the elongating RNA strand.2,3

TargetActionsOrganism
ARNA-directed RNA polymerase L
inhibitor
Zaire ebolavirus (strain Mayinga-76)
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half-life
Not Available
Clearance
Not Available
Adverse Effects
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Toxicity
Not Available
Affected organisms
Not Available
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.
Not Available
Food Interactions
Not Available

Products

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as pyrrolopyrimidines. These are compounds containing a pyrrolopyrimidine moiety, which consists of a pyrrole ring fused to a pyrimidine. Pyrrole is 5-membered ring consisting of four carbon atoms and one nitrogen atom. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyrrolopyrimidines
Sub Class
Not Available
Direct Parent
Pyrrolopyrimidines
Alternative Parents
Aralkylamines / Aminopyrimidines and derivatives / Substituted pyrroles / Imidolactams / Pyrrolidines / Heteroaromatic compounds / Secondary alcohols / 1,2-aminoalcohols / Dialkylamines / Azacyclic compounds
show 3 more
Substituents
1,2-aminoalcohol / Alcohol / Amine / Aminopyrimidine / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Heteroaromatic compound / Hydrocarbon derivative / Imidolactam
show 14 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
dihydroxypyrrolidine, pyrrolopyrimidine (CHEBI:46134)

Chemical Identifiers

UNII
OLF97F86A7
CAS number
249503-25-1
InChI Key
AMFDITJFBUXZQN-KUBHLMPHSA-N
InChI
InChI=1S/C11H15N5O3/c12-11-8-6(14-3-15-11)4(1-13-8)7-10(19)9(18)5(2-17)16-7/h1,3,5,7,9-10,13,16-19H,2H2,(H2,12,14,15)/t5-,7+,9-,10+/m1/s1
IUPAC Name
(2S,3S,4R,5R)-2-{4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl}-5-(hydroxymethyl)pyrrolidine-3,4-diol
SMILES

References

General 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]
  2. Westover JB, Mathis A, Taylor R, Wandersee L, Bailey KW, Sefing EJ, Hickerson BT, Jung KH, Sheridan WP, Gowen BB: Galidesivir limits Rift Valley fever virus infection and disease in Syrian golden hamsters. Antiviral Res. 2018 Aug;156:38-45. doi: 10.1016/j.antiviral.2018.05.013. Epub 2018 Jun 1. [PubMed:29864447]
  3. Eyer L, Nougairede A, Uhlirova M, Driouich JS, Zouharova D, Valdes JJ, Haviernik J, Gould EA, De Clercq E, de Lamballerie X, Ruzek D: An E460D Substitution in the NS5 Protein of Tick-Borne Encephalitis Virus Confers Resistance to the Inhibitor Galidesivir (BCX4430) and Also Attenuates the Virus for Mice. J Virol. 2019 Jul 30;93(16). pii: JVI.00367-19. doi: 10.1128/JVI.00367-19. Print 2019 Aug 15. [PubMed:31142664]
  4. Coronavirus treatment: Vaccines/drugs in the pipeline for Covid-19 [Link]
  5. BioCryst Initiates Phase 1 Clinical Trial of Galidesivir [Link]
  6. Galidesivir - BioCryst [Link]
PubChem Compound
10445549
PubChem Substance
347828044
ChemSpider
8620968
ChEMBL
CHEMBL1236524
ZINC
ZINC000013492903
PDBe Ligand
UA2
Wikipedia
Galidesivir
PDB Entries
2i4t / 4i72

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentMarburg Virus Disease1
1CompletedTreatmentEbola Virus Infection / Filovirus Infections1
1RecruitingTreatmentNovel Coronavirus Infectious Disease (COVID-19) / Yellow Fever1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility7.42 mg/mLALOGPS
logP-1.2ALOGPS
logP-2.1ChemAxon
logS-1.6ALOGPS
pKa (Strongest Acidic)12.95ChemAxon
pKa (Strongest Basic)8.46ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area140.31 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity67.29 m3·mol-1ChemAxon
Polarizability25.63 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein
Organism
Zaire ebolavirus (strain Mayinga-76)
Pharmacological action
Yes
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. Westover JB, Mathis A, Taylor R, Wandersee L, Bailey KW, Sefing EJ, Hickerson BT, Jung KH, Sheridan WP, Gowen BB: Galidesivir limits Rift Valley fever virus infection and disease in Syrian golden hamsters. Antiviral Res. 2018 Aug;156:38-45. doi: 10.1016/j.antiviral.2018.05.013. Epub 2018 Jun 1. [PubMed:29864447]
  2. Eyer L, Nougairede A, Uhlirova M, Driouich JS, Zouharova D, Valdes JJ, Haviernik J, Gould EA, De Clercq E, de Lamballerie X, Ruzek D: An E460D Substitution in the NS5 Protein of Tick-Borne Encephalitis Virus Confers Resistance to the Inhibitor Galidesivir (BCX4430) and Also Attenuates the Virus for Mice. J Virol. 2019 Jul 30;93(16). pii: JVI.00367-19. doi: 10.1128/JVI.00367-19. Print 2019 Aug 15. [PubMed:31142664]

Drug created on October 20, 2016 14:39 / Updated on June 12, 2020 10:53

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