A newly developed RNA molecule binds to SARS-CoV-2 virus and blocks its entry into cells
A research team from iNANO and Department of Molecular Biology and Genetics (Aarhus University) has used an in vitro selection technique to develop an RNA molecule that recognises and binds the Spike protein from SARS-CoV-2 with very high specificity and strength. The hope is that the new molecule, known as an RNA aptamer, can help improve diagnostics and treatment of COVID-19.
The past year and a half of COVID-19 pandemic has highlighted the importance of developing new molecules to diagnose and treat viral diseases. A new research article in Proceedings of the National Academy of Sciences (PNAS) from Julián Valero, Laia Civit, Jørgen Kjems and colleagues in Aarhus and in Regensburg in Germany describes the development of an RNA aptamer with very high binding affinity for the Spike protein that protrudes from the surface of SARS-CoV-2 virus particles. By attaching itself to the virus surface, the RNA aptamer prevents the Spike protein from serving as a key that allows the virus to enter a cell. The RNA aptamer folds into a 3D structure that makes it possible to recognize a specific target molecule of interest. In this way, aptamers can be compared to traditional antibodies, but they are much easier and cheaper to manufacture.
The new study shows that the aptamer efficiently blocks the binding between the Spike protein on the virus and the receptor ACE2 on human cells, thereby neutralising the infection of human cells grown in culture. The study also shows that the RNA aptamer inhibits the first known variants of the virus with comparable efficiency. “Since then, we have continued our studies and been able to show that it also recognizes the delta variant. We are now waiting for samples of the newly identified variant, omicron, so we can test whether the aptamer also recognizes that, ”says Jørgen Kjems.
The promising results point towards a possible future use of the aptamer in COVID-19 treatment and towards the development of cheaper and more sensitive diagnostic tests. Julian Valero, the first author on the paper, also highlights the applications beyond COVID-19: 'We can apply this technology to rapidly develop new RNA aptamer molecules targeting emerging SARS-CoV-2 variants or other viral threats'.
The Spike protein on the surface of SARS-CoV-2 virus (marked in red) recognises the hACE2 protein (marked in blue) that protrudes from healthy human cells in the throat and lungs. In this way, the Spike protein acts like a key that allows the virus to invade the cell and use its machinery to reproduce itself. The newly developed RNA aptamer (marked in yellow) binds the Spike protein very strongly and blocks it ability to recognise ACE2, thereby preventing further infection.
The research project is supported by the Carlsberg Foundation and by the EU FET-open project VIROFIGHT. Jørgen Kjems and Julián Valero are both affiliated with CellPAT, a center of excellence housed at iNANO and funded by the Danish National Research Foundation.
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External funding: Carlsberg foundation grant number CF20-0045, Danish National Research Foundation grant number DNRF135, EU Horizon2020 grant number 899619
Conflict of interest: The researchers declare that they have no conflict of interest
Other: Aarhus University has filed a patent for the new RNA aptamer
Link to the scientific article: https://www.pnas.org/content/118/50/e2112942118
Valero J *, Civit L, * Dupont DM, Selnihhin D, Reinert LS, Idorn M, Israels BA, Bednarz AM, Bus C, Asbach B, Peterhoff D, Pedersen FS, Birkedal V, Wagner R, Paludan SR, Kjems J: A serum-stable RNA aptamer specific for SARS-CoV-2 neutralizes viral entry. PNAS December 14, 2021 118 (50) e2112942118; doi.org/10.1073/pnas.2112942118.