remdesivir   Click here for help

GtoPdb Ligand ID: 10715

Synonyms: compound 4b [PMID: 28124907] | GS-5734 | GS5734 | Veklury®
Approved drug
remdesivir is an approved drug (FDA & EMA (2020))
Compound class: Synthetic organic
Comment: Remdesivir (GS-5734) is a nucleotide analogue drug that was developed by Gilead Sciences for antiviral potential, in particular for anti-Ebola and anti-Marburg virus activity [7]. It acts is an inhibitor of the viral RNA-dependent RNA polymerase (RdRP) that functions as a chain terminator during viral RNA synthesis. Remdesivir is a prodrug whose major active metabolite is GS-441524. Its 1'-CN group and C-linked nucleobase ensure optimal anti-Ebola potency and selectivity against host polymerase enzymes. Remdesivir has broad-spectrum activity against several viral families such as filoviruses, paramyxoviruses, and coronaviruses, and including the SARS and MERS coronaviruses (CoVs), endemic circulating human CoVs, and against SARS-CoV-2 [1-2,6]. The first patient to test positive for SARS-CoV-2 in the US was treated with i.v. remdesivir (using compassionate use of an investigational therapy prescribing) and his clinical condition improved significantly within the next 24h without observation of adverse effects [4].
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 12
Hydrogen bond donors 4
Rotatable bonds 14
Topological polar surface area 213.36
Molecular weight 602.23
XLogP 1.93
No. Lipinski's rules broken 2
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES CCC(COC(=O)[C@@H](N[P@@](=O)(Oc1ccccc1)OC[C@H]1O[C@@]([C@@H]([C@@H]1O)O)(C#N)c1ccc2n1ncnc2N)C)CC
Isomeric SMILES CCC(COC(=O)[C@@H](N[P@@](=O)(Oc1ccccc1)OC[C@H]1O[C@@]([C@@H]([C@@H]1O)O)(C#N)c1ccc2n1ncnc2N)C)CC
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
InChI Key RWWYLEGWBNMMLJ-YSOARWBDSA-N
References
1. Agostini ML, Andres EL, Sims AC, Graham RL, Sheahan TP, Lu X, Smith EC, Case JB, Feng JY, Jordan R et al.. (2018)
Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease.
mBio, 9 (2). DOI: 10.1128/mBio.00221-18 [PMID:29511076]
2. Gordon CJ, Tchesnokov EP, Woolner E, Perry JK, Feng JY, Porter DP, Götte M. (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 (20): 6785-6797. [PMID:32284326]
3. Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A, Feldt T, Green G, Green ML, Lescure FX et al.. (2020)
Compassionate Use of Remdesivir for Patients with Severe Covid-19.
N Engl J Med, 382 (24): 2327-2336. [PMID:32275812]
4. Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, Spitters C, Ericson K, Wilkerson S, Tural A et al.. (2020)
First Case of 2019 Novel Coronavirus in the United States.
N Engl J Med, 382 (10): 929-936. [PMID:32004427]
5. Lamb YN. (2020)
Remdesivir: First Approval.
Drugs, 80 (13): 1355-1363. [PMID:32870481]
6. Sheahan TP, Sims AC, Graham RL, Menachery VD, Gralinski LE, Case JB, Leist SR, Pyrc K, Feng JY, Trantcheva I et al.. (2017)
Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses.
Sci Transl Med, 9 (396). DOI: 10.1126/scitranslmed.aal3653 [PMID:28659436]
7. Siegel D, Hui HC, Doerffler E, Clarke MO, Chun K, Zhang L, Neville S, Carra E, Lew W, Ross B et al.. (2017)
Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses.
J Med Chem, 60 (5): 1648-1661. [PMID:28124907]
8. Wang Y, Anirudhan V, Du R, Cui Q, Rong L. (2021)
RNA-dependent RNA polymerase of SARS-CoV-2 as a therapeutic target.
J Med Virol, 93 (1): 300-310. [PMID:32633831]
9. Zhu W, Chen CZ, Gorshkov K, Xu M, Lo DC, Zheng W. (2020)
RNA-Dependent RNA Polymerase as a Target for COVID-19 Drug Discovery.
SLAS Discov, 25 (10): 1141-1151. [PMID:32660307]