Open questions on viral frameshifting: Exploiting the structural plasticity of the frameshifting element for therapeutic intervention.

Stephanie Portillo-Ledesma, Samuel Lee, Alain Laederach, Tamar Schlick

Abstract readReview

In one paragraph

Review in Biophysical journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it

0cells of the map it votes in

1citing papers in PubMed

–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

1 citing paper in PubMed.

VARIANT: Web Server for Decoding and Analyzing Viral Mutations at Genome and Protein Levels.ArXiv · 2026
Article

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

4 authors.

Stephanie Portillo-LedesmaDepartment of Chemistry, New York University, New York, NY, USA; Simons Center for Computational Physical Chemistry, New York University, New York, NY, USA.

Samuel LeeUniversity of Pennsylvania, Philadelphia, PA, USA.

Alain LaederachDepartment of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Tamar SchlickDepartment of Chemistry, New York University, New York, NY, USA; Courant Institute School of Mathematics, Computing, and Data Science, New York University, New York, NY, USA; New York University-East China Normal University Center for Computational Chemistry, New York University Shanghai, Shanghai, China; Simons Center for Computational Physical Chemistry, New York University, New York, NY, USA. Electronic address: schlick@nyu.edu.

Funding

Bridging Disparate Structural/Functional Scales: Multiscale Modeling of the Chromatin Fiber and RNA Tertiary StructuresR35GM122562 · NIGMS · NEW YORK UNIVERSITY · PI Tamar Schlick · 2017 to 2026

$4.6M

NIGMS NIH HHS R35 GM122562

6 · The paper itself

Abstract

Programmed ribosomal frameshifting (PRF) is a specialized controlled-slippage genetic mechanism that viruses such as SARS-CoV-2 and HIV-1 use to shift the reading frame during translation. This process is used in compact viral genomes to enhance their protein repertoire, maintain a precise balance of viral proteins necessary for successful replication, and enhance survival within a host. Because this mechanism is vital to the viral life cycle and remains consistent across strains, frameshifting has emerged as a promising therapeutic target for new antiviral therapeutic strategies. However, the complexity of the frameshifting process has posed many challenges that need to be addressed so that the relationship between cellular mechanisms and viral replication can be exploited for novel therapeutics. In this review, we introduce frameshifting mechanisms, define open questions being explored by many modeling and experimental studies, and illustrate how coarse-grained graphs have been used in our lab to study frameshifting mechanisms. Specifically, we describe how conformational landscapes, mutation designs of frameshifting elements, all-atom molecular dynamics, and enhanced sampling simulations have been combined with chemical mapping and functional experiments to advance studies of three viral systems employing -1 PRF: SARS-CoV-2, HIV-1, and chikungunya.

Indexed as

frameshifting efficiencyframeshifting elementsframeshifting mutantsRNA foldsRNA motifsviral frameshifting

Identifiers

PMID42157493

DOI10.1016/j.bpj.2026.05.025

PMCPMC13192295

What Socratic holds

Textmetadata

LicenceTDM

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 Socratic graph.