Aptamers for SARS‐CoV‐2: Isolation, Characterization, and Diagnostic and Therapeutic Developments

Abstract

The SARS‐CoV‐2 virus and COVID‐19 pandemic continue to demand effective diagnostic and therapeutic solutions. Finding these solutions requires effective molecular recognition elements. Nucleic acid aptamers represent a possible solution. Characterized by their high affinity and specificity, aptamers can be rapidly identified from random‐sequence nucleic acid libraries. Over the past two years, many labs around the world have rushed to create diverse aptamers that target two important structural proteins of SARS‐CoV‐2: the spike (S) protein and nucleocapsid (N) protein. These have led to the identification of many aptamers that show real promise for the development of diagnostic tests and therapeutic agents for SARS‐CoV‐2. Herein we review all these developments, with a special focus on the development of diverse aptasensors for detecting SARS‐CoV‐2. These include electrochemical and optical sensors, lateral flow devices, and aptamer‐linked immobilized sorbent assays.

Fluorescence-Linked Aptamer Assay for SARS-CoV-2 Spike-Protein: A Step-by-Step Performance Analysis in Clinical Samples

“…The FLAA test for SARS-CoV-2 S-protein detection was set in 96-well microplates as previously described [ 14 ]. Briefly, 100 pmole of 5′-amino-C6-modified C7 aptamer was immobilized on clear or black opaque Pierce™ maleic anhydride activated plates (Thermo Fisher Scientific, Waltham, MA, USA) as a capture agent.…”

“…Recently, aptamer recognition of S and N proteins as antigens has been used in the development of a wide range of biosensors due to nucleic acid’s capability to be coupled to nanomaterials employed in optical and electrochemical techniques [ 8 ]. Several SARS-CoV-2 aptasensors have been developed, including electrochemical and a variety of optical sensors such as lateral flow assays and aptamer-linked immobilized sorbent assays [ 14 ]. Many aptasensors have been tested with a limited number of clinical samples [ 15 , 16 , 17 , 18 ]; however, expensive instrumentation or too complicated systems probably limited their potential commercial application [ 14 ].…”

“…Several SARS-CoV-2 aptasensors have been developed, including electrochemical and a variety of optical sensors such as lateral flow assays and aptamer-linked immobilized sorbent assays [ 14 ]. Many aptasensors have been tested with a limited number of clinical samples [ 15 , 16 , 17 , 18 ]; however, expensive instrumentation or too complicated systems probably limited their potential commercial application [ 14 ]. Therefore, aptamer-based biosensor performance analysis under different clinical conditions is needed.…”

Angiotensin-converting enzyme 2-based biosensing modalities and devices for coronavirus detection

“…Some multimeric aptamers targeting S protein have shown pM affinities (2.1-2.3pM) [103], indicating a significant improvement in binding affinities compared to other sensing layers. Similarly, N protein-binding aptamers have also been reported [104], but S-binding aptamers are widely studied. In addition to improved binding constants, the aptamers are enticing in terms of higher thermal stability, smaller size, and easy and specific modifications [104].…”

“…Similarly, N protein-binding aptamers have also been reported [104], but S-binding aptamers are widely studied. In addition to improved binding constants, the aptamers are enticing in terms of higher thermal stability, smaller size, and easy and specific modifications [104]. In addition, a recent study reports on aptamers that can selectively bind different SARS-CoV-2 variants [105], paving the way towards the development of universal aptamer probes.…”