1 research outputs found
Three on Three: Universal and High-Affinity Molecular Recognition of the Symmetric Homotrimeric Spike Protein of SARS-CoV‑2 with a Symmetric Homotrimeric Aptamer
Our previously discovered monomeric aptamer for SARS-CoV-2
(MSA52)
possesses a universal affinity for COVID-19 spike protein variants
but is ultimately limited by its ability to bind only one subunit
of the spike protein. The symmetrical shape of the homotrimeric SARS-CoV-2
spike protein presents the opportunity to create a matching homotrimeric
molecular recognition element that is perfectly complementary to its
structural scaffold, causing enhanced binding affinity. Here, we describe
a branched homotrimeric aptamer with three-fold rotational symmetry,
named TMSA52, that not only possesses excellent binding affinity but
is also capable of binding several SARS-CoV-2 spike protein variants
with picomolar affinity, as well as pseudotyped lentiviruses expressing
SARS-CoV-2 spike protein variants with femtomolar affinity. Using
Pd–Ir nanocubes as nanozymes in an enzyme-linked aptamer binding
assay (ELABA), TMSA52 was capable of sensitively detecting diverse
pseudotyped lentiviruses in pooled human saliva with a limit of detection
as low as 6.3 × 103 copies/mL. The ELABA was also
used to test 50 SARS-CoV-2-positive and 60 SARS-CoV-2-negative patient
saliva samples, providing sensitivity and specificity values of 84.0
and 98.3%, respectively, thus highlighting the potential of TMSA52
for the development of future rapid tests