Evidence map›Paper›PMID 33124786›Full record

ArticlePharmacology research & perspectives2020

Nucleotide analogues as inhibitors of SARS-CoV Polymerase.

Jingyue Ju, Xiaoxu Li, Shiv Kumar, Steffen Jockusch, Minchen Chien, Chuanjuan Tao, Irina Morozova, Sergey Kalachikov, Robert N Kirchdoerfer, James J Russo

Open access · goldAbstract read
In one paragraph

Article in Pharmacology research & perspectives, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

63 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Current medicinal chemistry · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Frontiers in microbiology · 2023
    Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Jingyue JuCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, New York, USA.ORCID 0000-0002-4974-4241
Xiaoxu LiCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, New York, USA.
Shiv KumarCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, New York, USA.
Steffen JockuschCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, New York, USA.ORCID 0000-0002-4592-5280
Minchen ChienCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, New York, USA.
Chuanjuan TaoCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, New York, USA.
Irina MorozovaCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, New York, USA.
Sergey KalachikovCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, New York, USA.
Robert N KirchdoerferDepartment of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
James J RussoCenter for Genome Technology and Biomolecular Engineering, Columbia University, New York, New York, USA.
New York Genome Center · USColumbia University Irving Medical Center · USUniversity of Wisconsin–Madison · US

Funding

Structural Studies of the Corona Virus Life CycleR00AI123498 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI KIRCHDOERFER, ROBERT N · 2020 to 2021
$719k
Structural Studies of the Coronavirus Life CycleK99AI123498 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI KIRCHDOERFER, ROBERT N · 2017 to 2018
$207k
NIAID NIH HHS K99 AI123498NIAID NIH HHS R00 AI123498
6 · The paper itself

Abstract

SARS-CoV-2, a member of the coronavirus family, has caused a global public health emergency. Based on our analysis of hepatitis C virus and coronavirus replication, and the molecular structures and activities of viral inhibitors, we previously reasoned that the FDA-approved hepatitis C drug EPCLUSA (Sofosbuvir/Velpatasvir) should inhibit coronaviruses, including SARS-CoV-2. Here, using model polymerase extension experiments, we demonstrate that the active triphosphate form of Sofosbuvir is incorporated by low-fidelity polymerases and SARS-CoV RNA-dependent RNA polymerase (RdRp), and blocks further incorporation by these polymerases; the active triphosphate form of Sofosbuvir is not incorporated by a host-like high-fidelity DNA polymerase. Using the same molecular insight, we selected 3'-fluoro-3'-deoxythymidine triphosphate and 3'-azido-3'-deoxythymidine triphosphate, which are the active forms of two other anti-viral agents, Alovudine and AZT (an FDA-approved HIV/AIDS drug) for evaluation as inhibitors of SARS-CoV RdRp. We demonstrate the ability of two of these HIV reverse transcriptase inhibitors to be incorporated by SARS-CoV RdRp where they also terminate further polymerase extension. Given the 98% amino acid similarity of the SARS-CoV and SARS-CoV-2 RdRps, we expect these nucleotide analogues would also inhibit the SARS-CoV-2 polymerase. These results offer guidance to further modify these nucleotide analogues to generate more potent broad-spectrum anti-coronavirus agents.

Indexed as

Antiviral AgentsBetacoronavirusCarbamatesCoronavirus InfectionsCOVID-19DideoxynucleotidesDrug CombinationsHeterocyclic Compounds, 4 or More RingsHumansPandemicsPneumonia, ViralRNA-Dependent RNA PolymeraseSARS-CoV-2SofosbuvirThymine NucleotidesZidovudine3'-fluorothymidine-5'-triphosphateAntiviral AgentsCarbamatesDideoxynucleotidesDrug CombinationsHeterocyclic Compounds, 4 or More RingsRNA-Dependent RNA PolymeraseSofosbuvirsofosbuvir-velpatasvir drug combinationThymine NucleotidesZidovudinezidovudine triphosphateCOVID-19nucleotide analogueRNA-dependent RNA polymeraseSARS-CoVSARS-CoV-2

Identifiers

PMID33124786
PMCPMC7596664
OpenAlexW3096083800

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.