Related Experiment Video

Updated: Dec 8, 2025

Engineering Antiviral Agents via Surface Plasmon Resonance
13:00

Engineering Antiviral Agents via Surface Plasmon Resonance

Published on: June 14, 2022

2.6K

Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein

Christine Toelzer1,2, Kapil Gupta1,2, Sathish K N Yadav1,2

  • 1School of Biochemistry, University of Bristol, 1 Tankard's Close, Bristol BS8 1TD, UK.

Science (New York, N.Y.)
|September 22, 2020
PubMed

Insights

Linoleic acid (LA) binds to the SARS-CoV-2 spike protein, stabilizing its structure and reducing ACE2 interaction. This discovery may lead to new therapeutic strategies against COVID-19.

Area of Science:

  • Structural biology
  • Virology
  • Biochemistry

Background:

  • Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is a global health crisis.
  • Understanding SARS-CoV-2 mechanisms is crucial for developing effective therapeutics.
  • The spike (S) glycoprotein drives viral infectivity and pathology.

Purpose of the Study:

  • To elucidate the structural basis of SARS-CoV-2 infectivity.
  • To investigate the role of free fatty acids in S glycoprotein function.
  • To identify potential therapeutic targets for COVID-19.

Main Methods:

  • Cryo-electron microscopy at 2.85-angstrom resolution.
  • Structural analysis of the SARS-CoV-2 S glycoprotein.
  • In vitro assays to assess ACE2 interaction and viral replication.
  • Linoleic acid supplementation in human cells.

Main Results:

  • The SARS-CoV-2 S glycoprotein has three binding pockets for linoleic acid (LA).
  • LA binding stabilizes the S glycoprotein in a 'locked' conformation.
  • This conformation reduces interaction with angiotensin-converting enzyme 2 (ACE2) in vitro.
  • LA synergizes with remdesivir to suppress SARS-CoV-2 replication in human cells.
  • Similar LA binding pockets are suggested in SARS-CoV and MERS-CoV.

Conclusions:

  • Linoleic acid directly interacts with the SARS-CoV-2 spike protein.
  • LA binding represents a novel mechanism influencing viral entry and stability.
  • Targeting LA binding offers a potential therapeutic strategy for COVID-19 and related coronaviruses.

More Related Videos

A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation07:53

A Fluorogenic Peptide Cleavage Assay to Screen for Proteolytic Activity: Applications for coronavirus spike protein activation

Published on: January 9, 2019

33.6K
Production of Pseudotyped Particles to Study Highly Pathogenic Coronaviruses in a Biosafety Level 2 Setting08:40

Production of Pseudotyped Particles to Study Highly Pathogenic Coronaviruses in a Biosafety Level 2 Setting

Published on: March 1, 2019

59.5K

Related Concept Videos

Conserved Binding Sites01:49

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.9K
Conserved Binding Sites01:49

Conserved Binding Sites

1.9K
Lipids as Anchors01:32

Lipids as Anchors

In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are – prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains...
6.9K
Conjugated Proteins02:50

Conjugated Proteins

Simple proteins and protein complexes contain only amino acids. In contrast, many other proteins, called conjugated proteins, covalently bond with non-protein moieties.
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
25.0K
Ligand Binding Sites02:40

Ligand Binding Sites

Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
14.6K
Protein Folding01:22

Protein Folding

Overview
125.2K