Coronaviruses: A Scientist’s Race Against Time
Updated: Aug 30, 2020
By Saloni Chaurasia, Rockbridge High School, Columbia, MO
As the clock ticks, more and more people are falling victim to COVID-19, and scientists are racing against time to find treatment and prevention strategies. But what’s stopping them? The answer comes from two primary problems. Firstly, coronaviruses (CoVs) are transmitted from person-to-person via respiratory droplets from an infected person’s coughs or sneezes, which makes them highly contagious (CDC, How COVID-19 Spreads, 2020). This can happen in minutes, and up to 25% of patients remain asymptomatic (Du, et al., 2020). This makes it difficult for healthcare workers and researchers to contain patients and establish contact tracing to isolate the infected population. Secondly, it is hard to target CoVs without damaging our cells. CoVs infect via spike protein, which binds to the ACE2 receptor located on the lung alveolar epithelial cells (Hoffmann, et al., 2020). Once they invade the cell, CoVs hijack the host cell’s mechanisms to replicate. Thus, it is hard to combat the virus without damaging the host cell. On the other hand, recent understanding of CoVs structure and mechanism of action enables the scientific world to create a cure or vaccine. The bad news is that these efforts will likely face the perennial hurdles of medical innovation and discovery, long timelines of clinical trials for drug repurposing, and vaccine development, sometimes fickle funding, and changing governmental priorities.
What clinical trials are underway and what can we expect in the near future? Out of the tens of vaccines that are being tested worldwide, there are two that are promising in the United States. First, the biotechnology company Inovio Pharmaceuticals is developing a vaccine, INO-4800, for COVID-19. It uses a “DNA vaccine” approach, meaning INO-4800 delivers synthetic genes that code for proteins to ramp up the recipient’s immune response to COVID-19 (Inovio Pharmaceuticals, Inc., 2020). Inovio’s approach is advantageous due to prior experience with a similar CoV like the MERS vaccine (Inovio Pharmaceuticals, Inc., 2018). Second, the mRNA-1273 from Moderna is an “mRNA vaccine.” This mRNA technology injects snippets of genetic code into a person’s muscle to produce the specific viral proteins targeting COVID-19 structure, which allows the immune system to produce natural antibodies to combat the virus (National Institute of Allergy and Infectious Diseases, 2020). Both the vaccines are in Phase I clinical trials for safety and efficacy testing.
Yet, how do we cure the thousands infected with these fatal viruses? The best strategy is to repurpose existing antiviral drugs known for their safety and efficacy against COVID-19. Recently, hydroxychloroquine, an anti-malarial drug, was found to be effective in a French study but was redacted for violating clinical protocols (Gautret, et al., 2020). Further clinical trials are underway worldwide to ensure its effectiveness. There is a possibility of repurposing HIV drugs (Lopinavir and Ritonavir) reported to exhibit similar genomics and structure to COVID-19 and found to be beneficial in Thailand (Richardson, et al., 2020; Cao, et al., 2020). Another agent that appears to be promising against COVID-19 is Remdesivir, an investigational broad-spectrum antiviral drug, also known as GS-5734. It has been previously tested in humans with Ebola virus infections and in animal models for treating MERS and SARS. A University of Alberta study reported most of its patients had “rapid recoveries in fever and respiratory symptoms,” suggesting its potential (Gordon, et al., 2020). Next, several clinical trials are repurposing potential influenza drugs for COVID-19, such as Umifenovir, Baloxavir, and Favipiravir (Dong, Hu, & Gao, 2020). These drugs boost the immune system and enhance the body’s response to COVID-19. Lastly, scientists are also looking for convalescent plasma as a potential cure. The idea involves injecting plasma collected from treated COVID-19 patients who develop antibodies and transfuse into patients with active infections (Dall, 2020).
Figure 1. Possible treatment and prevention strategies to combat COVID-19 infection.
However, what is critical now more than ever is our preparation for the future, including early detection, antibody development for contact tracing, and isolating infected population. Each time the coronaviruses have struck, the outcomes have been deadlier than the previous. The recent COVID-19 pandemic shows our unpreparedness and, in turn, has taken a toll on our economy and healthcare systems. Thus, it is critical to understand CoV’s to prevent this pattern from continuing in the future.
Cao, B., Wang, Y., Wen, D., Liu, W., Wang, J., Wan, G., ... Xia, J. (2020). A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19. The New England Journal of Medicine. Retrieved from https://www.nejm.org/doi/10.1056/NEJMoa2001282
Dall, C. (2020, April 15). Antibody tests may hold clues to COVID-19 exposure, immunity-but it's complicated. Retrieved April 16, 2020, from https://www.cidrap.umn.edu/news-perspective/2020/04/antibody-tests-may-hold-clues-Covid-19-exposure-immunity-its-complicated
Dong, L., Hu, S., & Gao, J. (2020). Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discoveries & Therapeutics. doi: 10.5582/ddt.2020.01012.
Du, z J., Xu, x A., Wu, Y. undefined, Wang, L. undefined, Cowling, B. undefined, & Meyers, L. undefined. (2020). Serial Interval of COVID-19 among Publicly Reported Confirmed Cases. Emerging Infectious Diseases Journal - CDC, 19(26). doi: 10.3201/eid2606.200357
Gautret, P. (2020). Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. International Journal of Antimicrobial Agents. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/32205204
Gordon, C. J., Tchesnokov, E. P., Woolner, E., Perry, J. K., Feng, J. Y., Porter, D. P., & Gotte, M. (2020). Remdesivir is a direct-acting antiviral that inhibits RNA-dependent RNA polymerase from severe acute respiratory syndrome coronavirus 2 with high potency. Journal of Biological Chemistry. doi: 10.1074/jbc.RA120.013679
Hoffmann, M., Kleine-Weber, H., Schroeder, S., Kruger, N., Herrler, T., Erichsen, S., … Pohlmann, S. (2020). SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell, 181(271). Retrieved from https://www.cell.com/cell/pdf/S0092-8674(20)30229-4.pdf
How Coronavirus Spreads. (2020, April 13). Retrieved April 16, 2020, from https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/how-covid- spreads.html?CDC_AA_refVal=https://www.cdc.gov/coronavirus/2019- ncov/prepare/transmission.html
Inovio Pharmaceuticals, Inc. (2018, June 27). Inovio Selected by CEPI to Develop Vaccine Against New Coronavirus. Retrieved April 16, 2020, from http://ir.inovio.com/news-and-media/news/press-release-details/2018/Inovios-MERS-Vaccine-Generates-High-Levels-of-Antibodies-and-Induces-Broad-based-T-Cell-Responses-in-Phase-1-Study/default.aspx
Inovio Pharmaceuticals, Inc. (2020, January 23). Inovio Selected by CEPI to Develop Vaccine Against New Coronavirus. Retrieved April 16, 2020, from http://ir.inovio.com/news-and-media/news/press-release-details/2020/Inovio-Selected-by-CEPI-to-Develop-Vaccine-Against-New-Coronavirus/default.aspx
National Institute of Allergy and Infectious Diseases (NIAID). (2020, April 13). Safety and Immunogenicity Study of 2019-nCoV Vaccine (mRNA-1273) for Prophylaxis SARS CoV-2 Infection (COVID-19) - Full Text View. Retrieved April 16, 2020, from https://clinicaltrials.gov/ct2/show/NCT0428346
Richardson, P., Griffin, I., Tucker, C., Smith, D., Oechsle, O., Phelan, A., & Stebbing, J. (2020). Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. The Lancet, 395(10223). Retrieved from https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30304-4/fulltext