Researchers from Human Microbiology Institute (HMI) have discovered that prion-like domains contained in spike proteins of SARS-CoV-2 can contribute to an increased binding with human receptor ACE2.
This discovery could explain a very high transmission rate of the virus and why COVID-19 is so deadly. The study could also help evaluate new anti-prion compounds for anti-COVID19 therapeutic effects that are completely off the radar by pharmaceutical companies.
HMI specialists George Tetz and Victor Tetz suggest that prion-like domains are newly discovered regulators of virion assembly with a crucial role in virus-host cell interactions. The authors say that prion-like domains are extremely important for the new virus adhesion.
Using computational algorithms, these researchers discovered that, unlike other coronaviruses, SARS-CoV-2 has prion-like fragments in its receptor-binding domain of spike protein, particularly at the point where they interact with human ACE2 receptors.
Moreover, they identified prion-like domains of the ACE2 receptor that interacts with the viral receptor-binding domain of COVID-19 SARS2.
ACE2, which is short for angiotensin-converting enzyme 2, is a cell receptor that the coronavirus’ spike protein binds to. After the virus “docks” to the cell via ACE2, it penetrates the cell and begins to replicate, spreading to other cells at a very high pace.
The spike protein, Tetz says, sticks to the ACE2 receptor 10-20 times tighter compared to other coronaviruses that share the same receptor. This happens because the protein’s binding part has a “disordered region”. This misfolded protein structure and its “conformational stickiness” may explain the SARS-CoV-2 extremely high transmissibility.
The Human Microbiology Institute is the first group of researchers to point out that these prion-like domains could provide new insights into SARS-CoV-2 pathophysiology. The discovery could lead to novel targets for developing therapies and vaccines for the first time by implementing an anti-prion strategy for prion-like S protein – ACE2 interactions. Prophylaxis drugs could be also developed, for instance, for people who had contacts with COVID-19 patients.