Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Proofreading01:43

Proofreading

53.9K
Overview
53.9K
Improving Translational Accuracy02:07

Improving Translational Accuracy

9.4K
Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
9.4K
DNA Base Pairing02:27

DNA Base Pairing

27.2K
Erwin Chargaff’s rules on DNA equivalence paved the way for the discovery of base pairing in DNA. Chargaff’s rules state that in a double-stranded DNA molecule,
27.2K
Types of RNA01:23

Types of RNA

63.4K
Overview
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
63.4K
Nucleic Acid Structure01:25

Nucleic Acid Structure

6.1K
The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms  a 5′ to 3′ phosphodiester linkage.
DNA Structure
DNA...
6.1K
RNA Editing02:23

RNA Editing

8.9K
RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
8.9K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Ice-assisted cryogenic embrittlement grinding for surfactant-free fabrication of soft nanomaterials.

Materials horizons·2026
Same author

Site-Specifically Modified Circular Ribonucleic Acid Serves as Multitarget miRNA Sponge with Low Immunogenicity.

Journal of the American Chemical Society·2026
Same author

DNA Supramolecular Hydrogel Alters Exosomal microRNA Atlas and Paracrine Secretory Profile of MSCs to Promote Bone Remodeling and Ameliorate Osteoradionecrosis of the Jaw.

Advanced materials (Deerfield Beach, Fla.)·2026
Same author

Preparation strategies and biomedical applications of DNA hydrogels.

Chemical science·2026
Same author

Assessing conformation validity and rationality of deep learning-generated 3D molecules.

Nature communications·2026
Same author

Structure and mechanism of the human bile acid transporter OSTα-OSTβ.

Nature·2026

Related Experiment Video

Updated: Jun 14, 2025

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
10:29

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

465

Structural Basis and Rational Design of Nucleotide Analogue Inhibitor Evading the SARS-CoV-2 Proofreading Enzyme.

Junbo Wang1, Yufan Pan2, Yixiao Liu1

  • 1MOE Key Laboratory of Protein Science, School of Medicine, Tsinghua University, Beijing 100084, China.

Journal of the American Chemical Society
|June 13, 2025
PubMed
Summary

Nucleotide analogues (NAs) can evade SARS-CoV-2 nsp14 exoribonuclease (ExoN) cleavage. Modifications to the base and ribose moieties of NAs are key to evading nsp14 ExoN activity, informing antiviral drug design.

More Related Videos

Proofreading and DNA Repair Assay Using Single Nucleotide Extension and MALDI-TOF Mass Spectrometry Analysis
11:08

Proofreading and DNA Repair Assay Using Single Nucleotide Extension and MALDI-TOF Mass Spectrometry Analysis

Published on: June 19, 2018

9.7K
RNA Catalyst as a Reporter for Screening Drugs against RNA Editing in Trypanosomes
09:19

RNA Catalyst as a Reporter for Screening Drugs against RNA Editing in Trypanosomes

Published on: July 22, 2014

8.4K

Related Experiment Videos

Last Updated: Jun 14, 2025

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
10:29

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

465
Proofreading and DNA Repair Assay Using Single Nucleotide Extension and MALDI-TOF Mass Spectrometry Analysis
11:08

Proofreading and DNA Repair Assay Using Single Nucleotide Extension and MALDI-TOF Mass Spectrometry Analysis

Published on: June 19, 2018

9.7K
RNA Catalyst as a Reporter for Screening Drugs against RNA Editing in Trypanosomes
09:19

RNA Catalyst as a Reporter for Screening Drugs against RNA Editing in Trypanosomes

Published on: July 22, 2014

8.4K

Area of Science:

  • Virology
  • Molecular Biology
  • Drug Discovery

Background:

  • Coronaviruses (CoVs) utilize an exoribonuclease (nsp14 ExoN) to proofread nascent RNA, excising mismatched nucleotides or nucleotide analogues (NAs).
  • Understanding how NAs evade this proofreading mechanism is crucial for developing effective antiviral therapies against CoVs.

Purpose of the Study:

  • To investigate the mechanism by which SARS-CoV-2 nsp14 ExoN cleavage is evaded by specific nucleotide analogues (NAs).
  • To identify structural features of NAs that confer resistance to nsp14 ExoN activity.
  • To guide the rational design of novel anti-CoV NAs.

Main Methods:

  • Utilized chemically synthesized RNA incorporating various NAs at the 3' end.
  • Assessed the cleavage activity of SARS-CoV-2 nsp14 ExoN on these modified RNAs.
  • Determined cryo-electron microscopy structures of nsp10/14 complexes bound to RNA with NAs.
  • Performed mutagenesis studies on key residues within nsp14 ExoN.

Main Results:

  • Nsp14 ExoN showed significantly reduced activity on RNA containing sofosbuvir monophosphate (SMP) and AT-9010 monophosphate (ATMP) compared to natural nucleotides or other tested NAs.
  • Cryo-EM structures and mutagenesis revealed that residues H95, Q145, and F146 are critical for recognizing the base moiety and positioning NAs for cleavage.
  • NAs evade cleavage through a combination of a non-interacting base and a chemically modified ribose.

Conclusions:

  • The evasion of nsp14 ExoN cleavage by NAs is dependent on specific base-nucleotide interactions and ribose modifications.
  • Two novel NAs were designed based on these findings, demonstrating resistance to nsp14 ExoN cleavage.
  • These insights are valuable for the rational design of next-generation anti-coronavirus nucleotide analogues.