Discovery of Aptamers Targeting Receptor-Binding Domain of the SARS-CoV-2 Spike Glycoprotein

Abstract

The World Health Organization has declared the outbreak of a novel coronavirus (SARS-CoV-2 or 2019-nCoV) as a global pandemic. However, the mechanisms behind the coronavirus infection are not yet fully understood, nor are there any targeted treatments or vaccines. In this study, we identified high-binding-affinity aptamers targeting SARS-CoV-2 RBD, using an ACE2 competition-based aptamer selection strategy and a machine learning screening algorithm. The K<sub>d</sub> values of the optimized CoV2-RBD-1C and <a>CoV2-RBD-</a>4C aptamers against RBD were 5.8 nM and 19.9 nM, respectively. Simulated interaction modeling, along with competitive with experiments, suggests that two aptamers may have partially identical binding sites at ACE2 on SARS-CoV-2 RBD. These aptamers present an opportunity for generating new probes for recognition of SARS-CoV-2, and could provide assistance in the diagnosis and treatment of SARS-CoV-2 while providing a new tool for in-depth study of the mechanisms behind the coronavirus infection.

Feasibility of a silicon thin film transistor-based aptamer sensor for COVID-19 detection

“…An aptamer previously reported to bind to the spike protein of the COVID-19 virus was used [19]. The sequence is 5'-CAGCACCGACCTTGTGCTTTGGGAGTGCTGGTCCAAG GGCGTTAATGGACA-3'.…”

Aptamers for Detection and Diagnostics (ADD): Can mobile systems process optical data from aptamer sensors to identify molecules indicating presence of SARS-CoV-2 virus? Should healthcare explore aptamers as drugs for prevention as well as its use as adjuvants with antibodies and vaccines?

“…For SARS-CoV-2, there is a "baseline" interaction which could serve as a template for in silico design and prediction tool. ssDNA aptamers were identified to bind to the Spike (S) protein RBD (Song, Yanling, et al, 2020) and nucleocapsid (N) protein with affinity below 5 nM (one Kd 0.49 nM in Zhang, Liyun, et al, 2020). The in silico approach may model the parameters of the N protein using data/attributes relevant to the aptamers identified.…”

Aptamers for Detection and Diagnostics (ADD) is a proposed mobile app acquiring optical data from conjugated quantum nanodots to identify molecules indicating presence of SARS-CoV-2 virus: Why public health and healthcare need smartphone sensors as a platform for early detection and prevention

“…For SARS-CoV-2, there is a "baseline" interaction which could serve as a template for in silico design and prediction tool. ssDNA aptamers were identified to bind to the Spike (S) protein RBD (Song, Yanling, et al, 2020) and nucleocapsid (N) protein with affinity below 5 nM (one K d 0.49 nM in Zhang, Liyun, et al, 2020). The in silico approach may model the parameters of the N protein using data/attributes relevant to the aptamers identified.…”

“…Comparing the outcome of this challenge with the data from the reported (Song, Yanling, et al, 2020) binding of DNA aptamer with the S protein RBD, we can estimate the fit and reliability of the in silico model which used the data from the N protein as the template. What if the prediction of the in silico tool is incompatible with the reported aptamer that binds with the S protein?…”

“…To apply the algorithm in this case, the gulf between the predicted versus observed S protein binding aptamer needs to be narrowed down by pushing and pulling the in silico machine learning training tool to deliver the reported (Song, Yanling, et al, 2020) S protein binding aptamer sequence (based on the initial training of the in silico model using the N protein binding aptamer). Die-hard believers observe that "force fitting" in back propagation algorithm (BPA) is sort of similar to curve fitting of data to models 547 and mimics the induced fit mechanism of enzyme action (Koshland, 1958) representing biomimicry.…”