SARS-CoV-2 spike protein can specifically recognize the terminal sialic acid on sugars

The virus causing the current COVID-19 pandemic is the SARS-CoV-2. Soon after the pandemic outbreak in 2019, the ACE-2 protein, which is present on some of our cells´ surface, was identified as the receptor facilitating host cell viral entry.

However, this virus has a broad tropism, and it is in fact able to infect cells that do not contain the ACE-2 receptor on their surface. Because of that, from the scientific community many efforts have been made in order to identify additional molecular mechanisms that help the virus in its complex infection process. One of the possibilities that has been very much considered from the beginning is that the virus exploits the terminal sialic acids exposed on our cells´ surfaces as attachment factors or auxiliary/co-receptors.

This is actually the case for many known viral infections but had not yet been demonstrated for SARS-CoV-2. Sialic acids are sugars that decorate the terminal positions of complex glycans (sugars) on the surface of our cells. In the recent work of Chemical Glycobiology Group at CIC bioGUNE, published in Angewandte Chemie Int. Ed. (10.1002/anie.202201432) Unione et al. demonstrate for the first time that the Spike protein of SARS-CoV-2 is indeed able to specifically recognize the terminal sialic acid on sugars (sialoglycans).

The results, based on a 13C-glycan-labeling strategy and using Nuclear Magnetic Resonance (NMR) experiments, afford clear and non-ambiguous experimental evidence of the direct interaction between Spike and sialoglycans, which very likely entails important consequences in the infection process. These results, help us understanding the complex SARS-CoV-2 infection mechanism, and open new therapeutic opportunities directed towards inhibiting this interaction.