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DNA Aptamers Block the Receptor Binding Domain at the Spike Protein of SARS-CoV-2

preprint
submitted on 23.07.2020 and posted on 24.07.2020 by Fabrizio Cleri, Marc F. Lensink, Ralf Blossey

DNA aptamers are versatile molecular species obtained by the folding of short single-stranded nucleotide sequences, with highly specific recognition capabilities against proteins. Here we test the ability of selected DNA aptamers in interacting with the spike (S-)protein of the SARS-CoV-2 viral capsid. The S-protein, a trimer made up of several subdomains, develops the crucial function of recognizing the ACE2 receptors on the surface of human cells, and sub- sequent fusioning of the virus membrane with the host cell membrane. In order to do this, the S1 domain of one protomer switches between a closed conformation, in which the binding site is inaccessible to the cell receptors, and an open conformation, in which ACE2 can bind, thereby initiating the entry process of the viral genetic material in the host cell. Here we show by means of state-of-the-art molecular simulations that small DNA aptamers can recognize the S-protein of SARS-CoV-2. Moreover, their interaction with different regions of the S-protein can effectively block, or at least considerably slow down the opening process of the S1 domain, thereby largely reducing the probability of virus-cell binding. We also provide evidence that binding of the human ACE2 receptor may be drastically affected under such conditions. Given the facility and low cost of fabrication of specific aptamers, the present findings could open the way to both an innovative viral screening technique with sub-nanomolar sensitivity, and to an effective and low impact curative strategy.

History

Email Address of Submitting Author

fabrizio.cleri@univ-lille.fr

Institution

Universite de Lille

Country

France

ORCID For Submitting Author

0000-0003-0272-7441

Declaration of Conflict of Interest

Nothing to declare

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