ArticleACS central science2023
In Silico Discovery of Small Molecule Modulators Targeting the Achilles' Heel of SARS-CoV-2 Spike Protein.
Article in ACS central science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The trial behind it
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Who cites it
17 citing papers in PubMed, 43 citations in OpenAlex.
- A machine learning method for calculating highly localized protein stabilities.Nature communications · 2026Article
- Targeting SARS-CoV-2 Structural and Accessory Proteins: Emerging Opportunities for Small-Molecule Coronavirus Antivirals.Pharmaceutics · 2026Review
- Drugs against broad-spectrum of coronaviruses.Frontiers in immunology · 2026Review
- Molecular insights into species-specific ACE2 recognition of coronavirus HKU5.Nature communications · 2025Article
- Generative adversarial network (GAN) model-based design of potent SARS-CoV-2 MMolecular diversity · 2025Article
- Structure-based discovery of forsythoside A as an effective inhibitor to reduce the neurotoxicity of amyloid β.Communications chemistry · 2025Article
- In Silico Discovery of a Novel Antiviral Scaffold for SARS-CoV‑2 Targeting the Spike Glycoprotein through the Fatty Acid Binding Pocket.ACS omega · 2025Article
- Article
- High-Affinity Peptides for Target Protein Screened in Ultralarge Virtual Libraries.ACS central science · 2024Article
- AI Promoted Virtual Screening, Structure-Based Hit Optimization, and Synthesis of Novel COVID-19 S-RBD Domain Inhibitors.Journal of chemical information and modeling · 2024Article
- Identification and Ranking of Binding Sites from Structural Ensembles: Application to SARS-CoV-2.Viruses · 2024Article
- Exploring Binding Pockets in the Conformational States of the SARS-CoV-2 Spike Trimers for the Screening of Allosteric Inhibitors Using Molecular Simulations and Ensemble-Based Ligand Docking.International journal of molecular sciences · 2024Article
- Research Progress on Spike-Dependent SARS-CoV-2 Fusion Inhibitors and Small Molecules Targeting the S2 Subunit of Spike.Viruses · 2024Review
- Mechanistic insights into ligand dissociation from the SARS-CoV-2 spike glycoprotein.PLoS computational biology · 2024Article
- Spike Protein Mutation-Induced Changes in the Kinetic and Thermodynamic Behavior of Its Receptor Binding Domains Explain Their Higher Propensity to Attain Open States in SARS-CoV-2 Variants of Concern.ACS central science · 2023Article
- Different In Silico Approaches Using Heterocyclic Derivatives against the Binding between Different Lineages of SARS-CoV-2 and ACE2.Molecules (Basel, Switzerland) · 2023Article
- Identification of Potential Lead Compounds Targeting Novel Druggable Cavity of SARS-CoV-2 Spike Trimer by Molecular Dynamics Simulations.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The spike protein of SARS-CoV-2 has been a promising target for developing vaccines and therapeutics due to its crucial role in the viral entry process. Previously reported cryogenic electron microscopy (cryo-EM) structures have revealed that free fatty acids (FFA) bind with SARS-CoV-2 spike protein, stabilizing its closed conformation and reducing its interaction with the host cell target in vitro. Inspired by these, we utilized a structure-based virtual screening approach against the conserved FFA-binding pocket to identify small molecule modulators of SARS-CoV-2 spike protein, which helped us identify six hits with micromolar binding affinities. Further evaluation of their commercially available and synthesized analogs enabled us to discover a series of compounds with better binding affinities and solubilities. Notably, our identified compounds exhibited similar binding affinities against the spike proteins of the prototypic SARS-CoV-2 and a currently circulating Omicron BA.4 variant. Furthermore, the cryo-EM structure of the compound SPC-14 bound spike revealed that SPC-14 could shift the conformational equilibrium of the spike protein toward the closed conformation, which is human ACE2 (hACE2) inaccessible. Our identified small molecule modulators targeting the conserved FFA-binding pocket could serve as the starting point for the future development of broad-spectrum COVID-19 intervention treatments.
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.