ArticleProceedings of the National Academy of Sciences of the United States of America2021
Distant residues modulate conformational opening in SARS-CoV-2 spike protein.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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.
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.
Who cites it
58 citing papers in PubMed, 98 citations in OpenAlex.
- Scorpion Peptides in Antiviral Drug Discovery: An In-depth Review.Probiotics and antimicrobial proteins · 2026Review
- D614G reshapes allosteric networks and opening mechanisms of SARS-CoV-2 spikes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Identification of Key Residues in Allosteric Signaling of Photoactivated Adenylyl Cyclase.bioRxiv : the preprint server for biology · 2026Article
- Mutation and ACE2-induced allosteric network rewiring in Delta and Omicron SARS-CoV-2 spike proteins.Biophysical journal · 2026Article
- Understanding the conformational dynamics of PI3Kα due to helical domain mutations: insights from Markov state model analysis.Molecular diversity · 2025Article
- Cleaved versus Uncleaved: How furin cleavage reshapes the conformational landscape of SARS-CoV-2 spike.Protein science : a publication of the Protein Society · 2025Article
- Mutation and ACE2-induced Allosteric Network Rewiring in Delta and Omicron SARS-CoV-2 Spike Proteins.bioRxiv : the preprint server for biology · 2025Article
- Identification and understanding of allostery hotspots in proteins: Integration of deep mutational scanning and multi-faceted computational analyses.Journal of molecular biology · 2025Review
- An RGD motif on SARS-CoV-2 Spike induces TGF-β signaling and downregulates interferon.Journal of virology · 2025Article
- An Italian Single-Center Genomic Surveillance Study: Two-Year Analysis of SARS-CoV-2 Spike Protein Mutations.International journal of molecular sciences · 2025Article
- The Dynamical Asymmetry in SARS-CoV2 Protease Reveals the Exchange Between Catalytic Activity and Stability in Homodimers.Molecules (Basel, Switzerland) · 2025Article
- HCoVDB: a comprehensive database encompassing viral genomes, drug targets, and therapeutics of human coronaviruses.Database : the journal of biological databases and curation · 2025Article
- Decoding the cross-immune pressure: Dengue's role in SARS-CoV-2 evolution.Computational and structural biotechnology journal · 2025Article
- Dynamic expedition of leading mutations in SARS-CoV-2 spike glycoproteins.Computational and structural biotechnology journal · 2024Article
- Distinct pathways for evolution of enhanced receptor binding and cell entry in SARS-like bat coronaviruses.PLoS pathogens · 2024Article
- Article
- Mutations in the SARS-CoV-2 spike receptor binding domain and their delicate balance between ACE2 affinity and antibody evasion.Protein & cell · 2024Review
- Review
- Time dependent dihedral angle oscillations of the spike protein of SARS-CoV-2 reveal favored frequencies of dihedral angle rotations.Scientific reports · 2024Article
- Two-Stage Recognition Mechanism of the SARS-CoV-2 Receptor-Binding Domain to Angiotensin-Converting Enzyme-2 (ACE2).International journal of molecular sciences · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) involves the attachment of the receptor-binding domain (RBD) of its spike proteins to the ACE2 receptors on the peripheral membrane of host cells. Binding is initiated by a down-to-up conformational change in the spike protein, the change that presents the RBD to the receptor. To date, computational and experimental studies that search for therapeutics have concentrated, for good reason, on the RBD. However, the RBD region is highly prone to mutations, and is therefore a hotspot for drug resistance. In contrast, we here focus on the correlations between the RBD and residues distant to it in the spike protein. This allows for a deeper understanding of the underlying molecular recognition events and prediction of the highest-effect key mutations in distant, allosteric sites, with implications for therapeutics. Also, these sites can appear in emerging mutants with possibly higher transmissibility and virulence, and preidentifying them can give clues for designing pan-coronavirus vaccines against future outbreaks. Our model, based on time-lagged independent component analysis (tICA) and protein graph connectivity network, is able to identify multiple residues that exhibit long-distance coupling with the RBD opening. Residues involved in the most ubiquitous D614G mutation and the A570D mutation of the highly contagious UK SARS-CoV-2 variant are predicted ab initio from our model. Conversely, broad-spectrum therapeutics like drugs and monoclonal antibodies can target these key distant-but-conserved regions of the spike protein.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.