Targeting a conserved structural element from the SARS-CoV-2 genome using <scp>l</scp>-DNA aptamers
Jing Li, Jonathan T. Sczepanski
Abstract
values in the nanomolar range, and are capable of differentiating the monomeric s2m stem-loop from the proposed homodimer duplex. This structure-specific mode of recognition also allows l-C1t and l-C3t to discriminate between s2m RNAs from SARS-CoV-2 and SARS-CoV-1, which differ by just two nucleotides. Finally, we show that l-C1t and l-C3t induce dramatic conformational changes in s2m structure upon binding, and thus, have the potential to block protein-s2m interactions. Overall, these results demonstrate the feasibility of targeting SARS-CoV-2 RNA using l-aptamers, which has important implications in the diagnosis and treatment of COVID-19. Moreover, the high affinity and selectivity of l-C1t and l-C3t, coupled with the intrinsic nuclease resistance of l-DNA, present an opportunity for generating new tools and probes for interrogating s2m function in SARS-CoV-2 and related viruses.