DNA Aptamers Block the Receptor Binding Domain at the Spike Protein of SARS-CoV-2
2020
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.
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