Highly effective viral RdRP translocation hindrance by the remdesivir nucleotide

Clicks: 10
ID: 333005
2026
Free PDF
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Emerging

Ranked #1,185 of 1,248 articles by views in Nucleic Acids Research

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 1,248 in total.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
Nucleoside/nucleotide analogs (NAs) typically interfere with substrate selection and catalysis steps of polymerase nucleotide addition cycle (NAC), thereby affecting polymerase catalytic efficiency. In contrast, their interference with post-chemistry translocation is rarely considered in rational design, partly due to a lack of direct and quantitative evidence for such interference. Remdesivir (RDV) is an adenosine analog with broad-spectrum antiviral activity against diverse RNA virus families and has been approved for COVID-19 treatment. RDV is capable of inducing a characteristic "delayed" intervention, wherein the interference occurs several NACs after its incorporation. By combining X-ray crystallography, quench-flow kinetics, and molecular dynamics simulations, we show that the composite rate of RDV translocation from product strand position -3 to -4 and subsequent catalysis is at least 100-fold slower than that of adenosine in an enterovirus RdRP. However, mutating the corresponding roadblock residue serine417 to glycine largely abolishes this difference. Nonetheless, the incorporated RDV nucleotide can still alter the free-energy landscape even in the S417G mutant complex, enabling the capture of an over-translocated state. Our work demonstrates translocation-related intervention as an effective and broadly applicable polymerase intervention strategy in NA rational design.
Reference Key
openalex_W7222915387 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Rui Li, Qiang Shao, Meihua Wang, C. Feng, Xu Qin, Qisheng Wang, Luqing Shang, Yechun Xu, Peng Gong
Journal Nucleic Acids Research
Year 2026
DOI
10.1093/nar/gkag957
URL
https://doi.org/10.1093/nar/gkag957
Keywords Keywords not found

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.