Free fatty acid binding pocket in the locked structure of SARS-CoV-2 spike protein.
Level 5 - mechanism / opinion, no new human data
Bench research (cryo-electron microscopy and in vitro cell culture)
PubMed 32958580 · doi:10.1126/science.abd3255
What was done
Researchers determined the 2.85-angstrom cryo-electron microscopy structure of the SARS-CoV-2 spike glycoprotein to examine free fatty acid binding. They evaluated the effect of linoleic acid binding on spike conformation and angiotensin-converting enzyme 2 (ACE2) interaction in vitro, and assessed viral replication in human cell culture when linoleic acid was supplemented alone and combined with remdesivir.
What was found
The cryo-EM structure revealed that three composite pockets on the receptor-binding domains bind linoleic acid tightly, stabilizing a locked spike conformation and reducing ACE2 interaction in vitro. Similar pockets were observed for SARS-CoV and MERS-CoV. In human cells, linoleic acid supplementation synergized with remdesivir to suppress SARS-CoV-2 replication. Numerical effect sizes, binding constants, and replication inhibition metrics were not provided in the abstract.
Why it matters
The study uncovers a structural mechanism and conserved binding pocket on the coronavirus spike glycoprotein that locks it into a conformation less prone to receptor binding, providing a candidate target for therapeutic interventions.
Limits
The study is restricted to structural biology and in vitro cell models with no animal or human clinical data. The abstract does not report specific quantitative metrics, drug concentrations, or effect sizes, and it remains unknown whether physiological linoleic acid concentrations affect in vivo infection.
Cited by
- supports In silico molecular modeling demonstrated that DHA and linoleic acid can bind to the SARS-CoV-2 spike protein and stabilize it in a closed conformation, preventing receptor interaction.