By Gitanjali Alapati, James Clemens High School, Madison, AL
A deadly and mysterious virus that emerged at the end of 2019, called SARS CoV-2 (abbreviated for Severe Acute Respiratory Syndrome Coronavirus Virus-2), which is responsible for the disease COVID-19, has now led to a state of international emergency and is at the forefront of global discussion (“Naming The Coronavirus.” n.d.).
Transmission electron microscope image of an isolate taken from the first case of COVID-19 in the U.S.
Figure 1. Retrieved from Genetic Engineering and Biotechnology news, Coronavirus evolved naturally and ‘Is not a laboratory construct,’ genetic study shows. https://www.genengnews.com/wp-content/uploads/2020/03/23354_lores.jpg
The coronavirus belongs to the order of Nidovirales which have a characteristic feature of having enveloped and non-segmented positive RNA (similar to mRNA that can be easily translated to make proteins) segments. SARS CoV-2 when sequenced showed a total of 29,881 base pairs of RNA, consistent with the trend observed in the coronaviridae family that have approximately 30 kilo base pairs (kbp). Recent studies and researches have found that “similar to SARS-CoV, SARS CoV-2 also recognizes ACE2 [angiotensin converting enzyme 2] as its host receptor” (Tai, W. (2020, March 19). In fact, SARS CoV-2 shows a stronger binding affinity towards ACE2 than SARS CoV. The S protein, one of the structural proteins of coronavirus having two subunits: S1 and S2, identifies the receptor and binds to it to create the first binding to the cell and then mediate its entry into the cell through endocytosis to continue its cycle of replication. As the virus continues to replicate it destroys the healthy host cells (such as those in the respiratory tract) and mediates further into the lower airways and lungs that are more abundant with the ACE2 receptors thus leading to an infection far more complex than the common cold (Collins, S. 2020 March 20). It is also observed in all beta viruses (this includes SARS CoV-2) - a subgroup in coronavirus - that there is an additional fifth structural protein, (hemagglutinin-esterase protein) which further helps in the binding process by attaching to the Sialic acids present on the surface of the cells, particularly in the mucosal linings (found in the respiratory tracts), “to increase the efficiency of cell infection, either by improving viral binding initially or by enhancing virion release” (“Effects Of Sialic Acid.” 2016 December, 1).
Figure 2. Retrieved from The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – an update on the status. (2020). https://media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs40779-020-00240-0/MediaObjects/40779_2020_240_Fig1_HTML.png?as=webp
Similarities between SARS CoV-1 and SARS CoV-2:
Further analysis was conducted to look for similarities in the growth pattern in different Vero cells (a tissue culture platform with the cells derived from the epithelium of the kidney of African green monkey) with SARS CoV-2, to conclude finding “that SARS-CoV-2 maintains a similar profile to SARS-CoV in terms of susceptible cell lines” (Harcourt et al,. 2020 Jun). It is also observed that the antibodies of SARS CoV-1 cross interact with the S protein of SARS CoV-2 further emphasizing the similarity between the two. So now we ask the question: why don’t we use the same vaccines and antibodies against SARS CoV-2 that were once used against SARS CoV-1? The answer lies in the fact that even though both of these viruses show great similarities in the S protein, the S1 subunit of this protein, the main region where the vaccines and the antibodies were observed to show effect in SARS CoV-1, is different in both of them (Ou et al,. 2020, March 27).
The trend of the outbreak of the pandemics that are associated with the coronavirus is showing a decent gap of a decade or so and each time it is a new mutated version. SARS CoV-1 had its attack in 2002- 2003, while MERS had its attack in 2012, and now we have COVID-19 in 2019-2020. It is being suggested that the new virus is not laboratory made but instead a form of natural selection that is associated with the origin from the coronaviruses observed in bats and pangolins. This is similar to how the previous attacks have been made in association with the interaction of humans with civets in the case of SARS or camels in the case of MERS (Ktori, S. 2020, March 26). The close surveillance of the novel coronavirus suggests that even though the mutation rate of this virus is less compared to influenza it has been observed to show two strains: the L-type and the S-type, with the L-type being more aggressive and more common (70%) (Guo, Y. 2020, March 13).
Figure 3: Retrieved from Coronavirus COVID-19 (SARS-CoV-2). https://www.hopkinsguides.com/hopkins/repview?type=479-1124&name=2_538747_Standard.
The number of cases is increasing rapidly with varying mortality rates depending on factors such as age and pre-existing conditions, and there is no confirmed cure or medication. Recent studies have shown that the antimalarial drug chloroquine and a drug against rheumatoid arthritis called hydroxychloroquine can show a positive effect on the patients affected by SARS CoV-2. In a study conducted in France to 36 COVID-19 patients with 14 receiving the medication hydroxychloroquine, 6 receiving both hydroxychloroquine and azithromycin, and 16 as the control group, it was observed that “100% of patients receiving hydroxychloroquine with azithromycin were virologically cured, compared to 57.1% of patients receiving hydroxychloroquine alone and 12.5% of patients in the control group” (“Hydroxychloroquine.” 2020 March 27). The New York State “acquired 70,000 doses of hydroxychloroquine, 10,000 doses of azithromycin and 750,000 doses of chloroquine” so as to proceed with clinical trials in order to understand the dosage values and its administration. However, it is observed that the general public hoarded and used the medication without prescription, to which CDC warned the public that that could lead to “serious health consequences, including death” (Ornstein, C. 2020, April 1). The studies are being done and we can hope for a potential progress in the situation.
Figure 4: Retrieved from French Study Finds Antimalarial and antibiotic combo could reduce COVID-19 Duration.https://techcrunch.com/wp-content/uploads/2020/03/Hydroxychloroquine_final_DOI_IJAA-24-1038x553-1.jpg
It is not easy to stop nature from choosing its weapon, but it is up to us to be cautious and to protect ourselves and each other by maintaining social distance and breaking the contagion chain.
References
Collins, S. (2020, March 20). Coronavirus: What Happens When You Get Infected? Retrieved from https://www.webmd.com/lung/coronavirus-covid-19-affects-body
Coronavirus Disease 2019 (COVID-19). (2020, February 11). Retrieved from https://www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html
COVID-19 a Reminder of the Challenge of Emerging Infectious Diseases. (2020, February 28). Retrieved from https://www.nih.gov/news-events/news-releases/covid-19-reminder-challenge-emerging-infectious-diseases.
COVID-19 coronavirus epidemic has a natural origin. (n.d.). Retrieved from https://www.sciencedaily.com/releases/2020/03/200317175442.htm
Effects of Sialic Acid Modifications on Virus Binding and Infection. (2016, December 1). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123965/
Guo, Y. (2020, March 13). The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – an update on the status. Retrieved from https://mmrjournal.biomedcentral.com/articles/10.1186/s40779-020-00240-0
Harcourt J, Tamin A, Lu X, Kamili S, Sakthivel SK, Murray J, et al. Severe acute respiratory syndrome coronavirus 2 from patient with 2019 novel coronavirus disease, United States. Emerg Infect Dis. 2020 Jun [date cited]. https://doi.org/10.3201/eid2606.200516
Hydroxychloroquine for Potential Covid-19 Treatment. (2020, March 27). Retrieved from https://www.clinicaltrialsarena.com/projects/hydroxychloroquine/
Ktori, S. (2020, March 26). Coronavirus Evolved Naturally, and “Is Not a Laboratory Construct,” Genetic Study Shows. Retrieved from https://www.genengnews.com/news/coronavirus-evolved-naturally-and-is-not-a-laboratory-construct-genetic-study-shows/
Naming the coronavirus disease (COVID-19) and the virus that causes it. (n.d.). Retrieved from https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/naming-the-coronavirus-disease-(covid-2019)-and-the-virus-that-causes-it
Ornstein, C. (2020, April 1). What We Know - and Don't Know - About Possible Coronavirus Treatments Promoted by Trump. Retrieved from https://www.propublica.org/article/what-we-know-and-dont-know-about-possible-coronavirus-treatments-promoted-by-trump
Ou, X., Liu, Y., Lei, X., Li, P., Mi, D., Ren, L., … Qian, Z. (2020, March 27). Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Retrieved from https://www.nature.com/articles/s41467-020-15562-9
Tai, W. (2020, March 19). Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine. Retrieved from https://www.nature.com/articles/s41423-020-0400-4?error=cookies_not_supported&code=1ce4800e-5ae5-4d1b-9c6b-5a30a01c0f2e#Abs1
TechCrunch is now a part of Verizon Media. (2020, March 19). Retrieved from https://techcrunch.com/2020/03/19/french-study-finds-anti-malarial-and-antibiotic-combo-could-reduce-covid-19-duration/
Wan, Y. (2020, March 17). Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus. Retrieved from https://jvi.asm.org/content/94/7/e00127-20