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17th December 2021
An RNA aptamer which specifically binds to the spike protein and the receptor binding domain (RBD) of COVID-19 has been found to block entry of the virus into cells and could serve as a promising treatment for the virus, according to researchers from the Interdisciplinary Nanoscience Center, Aarhus University, Denmark.
RNA aptamers (RNA AP) are RNA oligonucleotides (i.e., single strands of RNA) that bind to a specific target with high affinity and specificity in much the same way that an antibody binds to an antigen and RNA aptamers have been used previously both diagnostically and therapeutically in the management of viruses.
For the present study, the Danish researchers described the development of a serum-stable RNA AP, RDB-PB6, which binds with nanomolar affinity to the RBD of the COVID-19 spike protein and in doing so, neutralises infectivity of the virus. The aptamer contains 2-fluoropyrimidine modifications which increases its chemical stability and resistance to degradation by viral nucleases. The researchers developed the RNA AP to specifically target the spike protein which is used by COVID-19 to bind with the angiotensin converting enzyme 2 (ACE2) to gain entry into cells. Their analysis revealed how RBD-PB6 bound with high affinity to the virus RBD alone but also interacted with the spike protein. The binding with the spike protein was confirmed in a separate experiment and again demonstrated that once bound to the spike protein, this complex was unable to interact with the ACE2 receptor.
Using virus-like particles the researchers were able to show that RBD-PB6 did not bind with other viruses such as the Middle East Respiratory syndrome (MERS) or Severe Acute Respiratory Syndrome (SARS) suggesting that the agent was highly specific, for COVID-19 displaying no cross-reactivity despite the similarity in the RBD sequence of these two coronaviruses.
Finally, the Danish team examined whether RBD-PB6 could bind to COVID-19 variants and tested this with the alpha and beta variants. They demonstrated high affinity binding between RBD-PB6 and the two variants indicating that these mutated strains were still able to recognise RBD-BP6.
The authors described how RBD-PB6 was very easy to mass produce and in a fast and reproducible way using conventional synthetic methods, adding that it was a potentially less expensive treatment compared to monoclonal antibodies. They concluded that their RNA aptamer provided a promising lead for COVID-19 treatment and a cost-effective platform for the rapid diagnosis of the virus.
Valero J et al. A serum-stable RNA aptamer specific for SARS-CoV-2 neutralizes viral entry PNAS 2021