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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Remdesivir (GS-5734) must be administered by intravenous (i.v.) infusion. Remdesivir progressed to Phase 2 evaluation in Ebola infected patients. It is to be evaluated for efficacy in the treatment of the novel coronavirus (SARS-CoV-2) infection COVID-19, with 4 Phase 3 trials registered on ClinicalTrials.gov as of early March 2020. Grein et al. published results from short-term compassionate-use remdesivir in hospitalised COVID-19 patients (receiving invasive ventilation or ECMO) in the NEJM in April 2020 [3]. Whilst this study indicated some clinical benefit, and detected no additional safety signals, it was not powered to conclusively determine clinical efficacy. The study did not measure the effect of remdesivir on viral load, and it was not placebo-controlled. In some cases remdesivir seems to shorten the time to recovery. Despite limited data on efficacy, the FDA granted full approval in October 2020, for the treatment of hospitalised COVID-19 patients [5]. This was quite unexpected because the FDA based their decision on data from a set of studies that were not suitably designed or controlled, and gave mixed results. It remains the case that larger controlled trials are needed.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Remdesivir is a phosphoramidate adenosine nucleotide analogue that blocks viral RNA-dependent RNA polymerase (RdRp) function and thereby reduces viral RNA production. It is not detected by the viral proofreading enzyme, exoribonuclease (ExoN).
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04252664 Mild/Moderate 2019-nCoV Remdesivir RCT Phase 3 Interventional Capital Medical University
NCT04257656 Severe 2019-nCoV Remdesivir RCT Phase 3 Interventional Capital Medical University
NCT02818582 GS-5734 to Assess the Antiviral Activity, Longer-Term Clearance of Ebola Virus, and Safety in Male Ebola Survivors With Evidence of Ebola Virus Persistence in Semen Phase 2 Interventional National Institutes of Health Clinical Center (CC)