The world is currently gripped by the novel COVID-19 crisis caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is a highly pathogenic viral respiratory illness. It is an enveloped positive sense single stranded RNA virus that enters its host by binding to the ACE2 receptor (Figure 1). Two strains of the virus have caused outbreaks of severe respiratory diseases in humans:
- SARS-CoV(or SARS-CoV-1), which caused an outbreak of severe acute respiratory syndrome (SARS) between 2002 and 2003, and
- SARS-CoV-2, which has caused the 2019–20 pandemic of coronavirus disease 2019 (COVID-19)
Figure 1. Schematic representation of coronavirus structure and viral receptor ACE2 on the host cell surface.
Currently, viral infection is a serious threat for human beings. With almost 465,915 confirmed cases of COVID-19 worldwide with 21,031 deaths as of 27th March 2020 as per WHO, accurate and early detection of such viruses is highly crucial for clinical diagnosis and therapeutics. Currently there are few specific antiviral strategies, but several potent candidates of antivirals agents are under urgent investigation. Although antibody-based detection methods and drugs are widely used in clinics, their popularity is hindered by high cost, antibody instability and the limitation of target types.
Aptamer-based assay for virus detection have shown to improve these drawbacks and have proven to be of great potential as a feasible tool in virus detection and therapeutics due to their properties such as:
- Easy to synthesize and easy to screen
- Stable in different environmental conditions
- Selected aptamers are capable of adapting unique tertiary structures
- Recognize target molecules with high affinity and specificity
- Can be modified chemically at defined positions and linked stably to solid surfaces
- Can be reproducibly obtained in large quantities and at a low cost
Thus, aptamers have been considered as potentially useful diagnostic agents and are promising for detecting viruses and treating viral infections. Taking advantage of the highly specific aptamers, two independent research groups have demonstrated the application of aptamers in detection and therapeutics of SARS CoV.
Ahn et al. developed an aptasensor to detect severe acute respiratory syndrome coronavirus (SARS-CoV), with an aptamer capturing the SARS-CoV N protein using chemiluminiscence immunosorbent (CL) assay. An enzyme-labeled secondary antibody to the N protein was employed to transduce the signal. This aptasensor detected SARS-CoV N protein at levels as low as 2 pg/ml (Figure 2).
Figure 2. Fluorescence detection of N protein by a nanoarray aptamer chip.
Aptamers have also been selected against enzymes associated with SARS CoV (SCV) that might be potentially useful as anti-SCV agents by binding and inhibiting the enzyme activity in vitro. Such enzymes have shown to contain helicase activity of unwinding dsDNA with a 5’ to 3’ polarity and a potential target in other viruses due to their indispensability in viral genome replication. In this view, Jang et al. isolated an RNA aptamer (ES15 RNA) against SARS CoV (SCV) NTPase/ Helicase [nsP10] that could efficiently bind and inhibit nucleic acid unwinding activity of the helicase by up to 85% with a slight effect of ATPase activity on the protein (Figure 3).
Figure 3. Principle of FRET-based helicase assay and inhibition of the SCV helicase activity by the ES15 RNA. More efficient inhibition of SCV helicase activity was observed with ES15 RNA by up to ∼85%, whereas the random RNA library exhibited little inhibition.
Overall, aptamers could provide a strong tool for the expansion of new diagnostic and therapeutic factors in virus infections with negligible side effects as compared to traditional antibodies. Since the outbreak of the novel coronavirus disease COVID-19, caused by the SARS-CoV-2 virus, this disease has spread rapidly around the globe. The poor clinical outcome proves the high severity of the disease.
At, Aptamer Group Ltd, our scientists are continuously working to develop an aptamer binder selective for the spike protein in SARS CoV-2 which we expect to complete in 3-4 weeks. Our aim is to work this into a point-of-use test for the detection of virus itself, and have a proof-of-concept in two months. Please contact us using the form below if you would like more information and if this is something that you’d like to get involved in.
Ahn D. G., Jeon I. J., Kim J. D., Song M. S., Han S. R., Lee S. W., et al. (2009). RNA aptamer-based sensitive detection of SARS coronavirus nucleocapsid protein. Analyst 134, 1896–1901. 10.1039/b906788d
Jang KJ, Lee NR, Yeo WS, Jeong YJ, Kim DE. Isolation of inhibitory RNA aptamers against severe acute respiratory syndrome (SARS) coronavirus NTPase/Helicase. (2008) Biochem Biophys Res Commun.;366(3):738–744. doi:10.1016/j.bbrc.2007.12.020