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In a new study, researchers found a druggable pocket in the SARS-CoV-2 Spike protein could be used to stop the virus from infecting human cells.
The findings are a potential ‘game-changer’ in defeating the current pandemic and add that small-molecule anti-viral drugs developed to target the pocket they discovered could help eliminate COVID-19. The research was conducted by a team at the University of Bristol and elsewhere.
SARS-CoV-2 is decorated by multiple copies of a glycoprotein, known as the ‘Spike protein’, which plays an essential role in viral infectivity.
Spike binds to the human cell surface, allowing the virus to penetrate the cells and start replicating, causing widespread damage.
In this ground-breaking study, the team used a powerful imaging technique to analyze SARS-CoV-2 Spike at near-atomic resolution.
Enabled by Oracle high-performance cloud computing, a 3-D structure of SARS CoV-2 Spike protein was generated allowing the researchers to peer deep inside the Spike identifying its molecular composition.
Unexpectedly, the team found the presence of a small molecule, linoleic acid, buried in a tailor-made pocket within the Spike protein.
linoleic acid is a free fatty acid, which is indispensable for many cellular functions. The human body cannot produce linoleic acid. Instead, the body absorbs this essential molecule through diet.
Intriguingly, linoleic acid plays a vital role in inflammation and immune modulation, which are both key elements of COVID-19 disease progression.
Linoleic acid is also needed to maintain cell membranes in the lungs so that we can breathe properly.
The team says linoleic acid is at the center of those functions that go haywire in COVID-19 patients, with terrible consequences.
From other diseases, scientists know that tinkering with linoleic acid metabolic pathways can trigger systemic inflammation, acute respiratory distress syndrome, and pneumonia.
These pathologies are all observed in patients suffering from severe COVID-19. A recent study of COVID-19 patients showed markedly reduced linoleic acid levels in their sera.
The discovery provides the first direct link between linoleic acid, COVID-19 pathological manifestations, and the virus itself.
The question now is how to turn this new knowledge against the virus itself and defeat the pandemic.
One author of the study is Professor Christiane Schaffitzel from Bristol’s School of Biochemistry.
The study is published in Science.
