Evidence map›Paper›PMID 22615777›Full record

ArticlePloS one2012

Mechanism of nucleic acid unwinding by SARS-CoV helicase.

Adeyemi O Adedeji, Bruno Marchand, Aartjan J W Te Velthuis, Eric J Snijder, Susan Weiss, Robert L Eoff, Kamalendra Singh, Stefan G Sarafianos

Abstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
121citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

121 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Journal of enzyme inhibition and medicinal chemistry · 2025
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. High throughput screening for SARS-CoV-2 helicase inhibitors.SLAS discovery : advancing life sciences R & D · 2024
    Article
  17. Article
  18. Article
  19. Article
  20. Article

61 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

8 authors.

Adeyemi O AdedejiChristopher Bond Life Sciences Center, Department of Molecular Microbiology and Immunology, University of Missouri, School of Medicine, Columbia, Missouri, United States of America.
Bruno Marchand
Aartjan J W Te Velthuis
Eric J Snijder
Susan Weiss
Robert L Eoff
Kamalendra Singh
Stefan G Sarafianos

Funding

Gene Therapy for HIV Using Aptamers that Target Reverse TranscriptaseR01AI074389 · NIAID · UNIVERSITY OF MISSOURI-COLUMBIA · PI BURKE, DONALD H · 2008 to 2017
$4.5M
Ultrapotent Inhibitors of Wild-type and Multi-drug Resistant HIVR01AI076119 · NIAID · UNIVERSITY OF MISSOURI-COLUMBIA · PI SARAFIANOS, STEFAN G · 2008 to 2018
$4.1M
Ultrapotent Inhibitors of Wild-type and Multi-drug Resistant HIVR37AI076119 · NIAID · EMORY UNIVERSITY · PI Stefan G Sarafianos · 2020 to 2026
$3.6M
Microbicide properties of RT inhibitor combinationsR33AI079801 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI PARNIAK, MICHAEL A · 2010 to 2012
$1.4M
Microbicide properties of RT inhibitor combinationsR21AI079801 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI PARNIAK, MICHAEL A · 2008 to 2009
$421k
Structure-based expansion of neutralization ability of KD-247, an anti-V3 mAbR21AI094715 · NIAID · UNIVERSITY OF MISSOURI-COLUMBIA · PI SARAFIANOS, STEFAN G · 2010 to 2011
$415k
CIHRNIAID NIH HHS AI074389NIAID NIH HHS AI076119NIAID NIH HHS AI079801NIAID NIH HHS AI094715NIAID NIH HHS R01 AI074389NIAID NIH HHS R01 AI076119NIAID NIH HHS R21 AI079801NIAID NIH HHS R21 AI094715NIAID NIH HHS R33 AI079801NIAID NIH HHS R37 AI076119
6 · The paper itself

Abstract

The non-structural protein 13 (nsp13) of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is a helicase that separates double-stranded RNA (dsRNA) or DNA (dsDNA) with a 5' → 3' polarity, using the energy of nucleotide hydrolysis. We determined the minimal mechanism of helicase function by nsp13. We showed a clear unwinding lag with increasing length of the double-stranded region of the nucleic acid, suggesting the presence of intermediates in the unwinding process. To elucidate the nature of the intermediates we carried out transient kinetic analysis of the nsp13 helicase activity. We demonstrated that the enzyme unwinds nucleic acid in discrete steps of 9.3 base-pairs (bp) each, with a catalytic rate of 30 steps per second. Therefore the net unwinding rate is ~280 base-pairs per second. We also showed that nsp12, the SARS-CoV RNA-dependent RNA polymerase (RdRp), enhances (2-fold) the catalytic efficiency of nsp13 by increasing the step size of nucleic acid (RNA/RNA or DNA/DNA) unwinding. This effect is specific for SARS-CoV nsp12, as no change in nsp13 activity was observed when foot-and-mouth-disease virus RdRp was used in place of nsp12. Our data provide experimental evidence that nsp13 and nsp12 can function in a concerted manner to improve the efficiency of viral replication and enhance our understanding of nsp13 function during SARS-CoV RNA synthesis.

Indexed as

DNA HelicasesNucleic AcidsSevere acute respiratory syndrome-related coronavirusSubstrate SpecificityDNA HelicasesNucleic Acids

Identifiers

PMID22615777
PMCPMC3352918

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.