Could NSP13 be the target to help treat some respiratory infections such as SARS-CoV-2? Respiratory diseases caused by coronaviruses (CoVs) vary in symptoms, severity, and risk. Typically, symptoms are mild and known as the common cold, while others are more severe and lead to pneumonia or bronchitis, chest pains, and possibly death.
SARS-CoV and MERS-CoV have caused severe respiratory illness with novel outbreaks leading to severe symptoms from patient immune systems not being familiar with the new viruses. This is the case with COVID-19, which has killed more than half a million people in the US within the first year of the pandemic. There’s a wide range of symptoms and severity for those infected with COVID-19, with some not reporting any symptoms at all. Still, there’s no doubt that regardless of the types of symptoms or severity of disease, everyone’s lives have been affected whether mentally, physically, or economically.2
While the viral host has cellular proteins that detect, activate, and fight viruses, there are also a variety of proteins that allow the virus to thrive and replicate. The NTPase and RNA helicase that can unwind double-stranded nucleic acid, a necessary step in replication, transcription, and translation, is a functional component of the non-structural protein 13 (NSP13) found in CoVs including COVID-19 that can be exploited to fight the disease. 1 Furthermore, NSP13 is a conserved protein found in the CoV family, making it an ideal target for not only COVID-19 antiviral therapy but future novel CoVs. 3 Researchers have found that NSP13 has a strong affinity for duplex RNA as a substrate for the unwinding reaction with increased ATP.1
The Search for NSP13 Inhibitors
Viral helicase inhibitors have been used to treat the herpes simplex virus (HSV) and hepatitis C due to the inhibition of helicase activity.1 Additionally, researchers have already started discovering potential NSP13 helicase inhibitors to treat CoVs. Of particular interest, White, et al. utilized an NSP13 activity assay to study several possible inhibitors at once and found two molecules with significant inhibiting ability towards the SARS-CoV-2 helicase. 3
The Transcreener® ADP² Kinase Assay can detect the enzymatic activity of Kinases, ATPases, helicases, and any enzyme that produces ADP; consequently, it is a fit for the continued research into NSP13.
Continuing the search for inhibitors and other antiviral therapies that will not only assist with the current pandemic but could immediately be used in the next pandemic is extremely important. It could make the next pandemic easier to manage earlier on in the outbreak.
- Jang, K., Jeong, S., Kang, D. Y., Sp, N., & Yang, Y. M. (2020). OPEN A high ATP concentration enhances the cooperative translocation of the SARS coronavirus helicase nsP13 in the unwinding of duplex RNA. Scientific Reports, 1–13. https://doi.org/10.1038/s41598-020-61432-1
- Shu, T., Huang, M., Wu, D., Ren, Y., Zhang, X., Han, Y., & Mu, J. (2020). SARS-Coronavirus-2 Nsp13 Possesses NTPase and RNA Helicase Activities That Can Be Inhibited by Bismuth Salts, 12250, 321–329. https://doi.org/10.1007/s12250-020-00242-1
- White, M. A., Lin, W., & Cheng, X. (2020). Discovery of COVID-19 Inhibitors Targeting the SARS-CoV ‑ 2 Nsp13 Helicase. https://doi.org/10.1021/acs.jpclett.0c02421