The final piece in our three-part series on the massive world-wide research response to the COVID-19 pandemic will look at the therapeutic targets, neutralization antibodies, and inhibitors that could end the pandemic. Part 1 examined how we came to understand the virus and the human host response, and Part 2 covered research into potential diagnostics and vaccines for SARS-CoV-2.
As the coronavirus pandemic case count and death toll continues to rise, researchers have been urgently pursuing COVID-19 therapeutics throughout 2020 and early 2021. With the critical need to provide overworked doctors and nurses with tools to treat their patients, the identification of therapeutic targets, neutralization antibodies, and inhibitors moved rapidly forward, even while little was known about the novel coronavirus.
Identifying targets for therapeutic development
As more was learned about how SARS-CoV-2 suppresses the human immune system’s antiviral response, researchers became concerned about a clinical trial that was already underway using interferons to treat COVID-19 patients. Because interferons increase production of ACE2 – which SARS-CoV-2 uses to enter the cell – some scientists feared that using interferon therapeutics could in fact increase the capability of the virus to infect its host. Using Western blots and the Odyssey CLx Imaging System, a group from the Institute of Medical Virology, ETH Zurich, and the University of Zurich, all in Switzerland, took a closer look at interferons as possible targets for therapeutic development for people who contract COVID-19. Fortunately, they found that the antiviral activity of interferons against the novel coronavirus offsets the proviral impacts of the ACE2 binding capability, concluding in their September 2020 paper1 in mBio that specific interferons are strong potential COVID-19 therapeutics.
Another study identifying a potential targeted therapeutic, published in a January 2020 issue of The Journal of Cell Science2, first looked more deeply at the mechanism of action for SARS-CoV-2. The authors, an international group from the University of Manchester in the United Kingdom, Ball State University in Indiana, and the University of Maryland in College Park, relied heavily on a large number of Western blots and the Odyssey CLx Imaging System for data in their project. Importantly, their paper describes the potential for endoplasmic reticulum translocation inhibitors to act as general antiviral therapeutics.
Searching for neutralizing antibodies and inhibitors of SARS-CoV-2
Aside from identifying therapeutic targets for treating COVID-19, researchers have also been searching for neutralizing antibodies that could defend cells against SARS-CoV-2 invasion. For instance, one study published in January 2021 in The Journal of Virological Methods described what the authors – an international team from the Texas Biomedical Research Institute in San Antonio, the University of Ilorin in Nigeria, the University of Alabama in Birmingham, and the Icahn School of Medicine – called a “rapid, accurate, and highly reproducible” assay3 that could identify and characterize neutralizing antibodies and antivirals. Their paper includes exceptional images of the In-Cell Western Assay, and they used the Odyssey Sa Imaging System for their research.
In a final example of the past year’s pursuit of COVID-19 therapeutics, a group of researchers from the National Institutes of Health’s National Cancer Institute in Frederick, MD, published their findings that identified potential inhibitors of SARS-CoV-2. Their study4, published online in January 2021 by the journal Virus, includes two-color Western blots and describes using the Odyssey CLx Imaging System to develop a new assay that identifies potent inhibitors of the virus causing COVID-19. The new assay could expedite identification of targets for antiviral therapeutics.
Unprecedented pace of global discovery provides necessary research and data
The massive scope of the scientific community’s response to the seemingly overwhelming challenge presented by the coronavirus pandemic has led to timely and necessary discoveries in the field of COVID-19 therapeutics. Moreover, at the same time that new therapeutics were being studied, researchers were also adding to our basic understanding of SARS-CoV-2 and the human host response as well as developing diagnostic tools and vaccines. Over the course of this three-part series, we’ve seen how research from 31 institutions across Africa, North America, Asia, and Europe have contributed to this urgent research effort. LI-COR technology was used for Western blots, neutralization assays, peptide arrays and more in the world-wide endeavor to understand this virus and diagnose, prevent, and treat the disease it causes. Why not find out what LI-COR can do for your research?
References
- Busnadiego, I., Fernbach, S., Pohl, M. O., Karakus, U., Huber, M., Trkola, A., et. al. (2020). Antiviral activity of type I, II, and III interferons counterbalances ACE2 inducibility and restricts SARS-CoV-2. MBio, 11(5). DOI: 10.1128/mBio.01928-20
- O’Keefe, S., Roboti, P., Duah, K. B., Zong, G., Schneider, H., Shi, W. Q., & High, S. (2021). Ipomoeassin-F inhibits the in vitro biogenesis of the SARS-CoV-2 spike protein and its host cell membrane receptor. Journal of Cell Science, 134. DOI: 10.1242/jcs.257758
- Park, J.-G., Oladunni, F. S., Chiem, K., Ye, C., Pipenbrink, M., Moran, T., et.al. (2021). Rapid in vitro assays for screening neutralizing antibodies and antivirals against SARS-CoV-2. Journal of Virological Methods, 287. DOI: 10.1016/j.jviromet.2020.113995
- Rawson, J. M. O., Duchon, A., Nikolaitchik, O. A., Pathak, V. K., & Hu, W.S. (2021). Development of a cell-based luciferase complementation assay for identification of SARS-CoV-2 3CLpro inhibitors. Viruses, 13(2), 173. DOI: 10.3390/v13020173
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