Coronavirus – An Unsolvable Challenge?

“So we have a virus with no treatment protocol, and no vaccine at this time.”
– Dr. Erin Mears (starred by Kate Winslet), Contagion, 2011

COVID-19 (Coronavirus disease 19) has again pointed at the fact that maybe we are not at all ready to cope with adversities caused due to how we interact with nature. The number of victims is increasing dangerously. According to the statistics obtained from an online source [1], it took 67 days for the total number of coronavirus victims to reach 1 lakh (from 31 December 2019, when COVID-19 was reported in China [2]), twelve more days to cross 2 lakh, four more days to cross 3 lakh, and as of 25 March 2020, it has crossed 4 lakh 45 thousand globally, only in four more days. According to the World Health Organisation, all 195 countries in the world are affected.

Why is this virus so infectious?

For a start, let’s try to understand what a coronavirus actually is, along with why and how one of its sub-types, SARS-CoV-2, has become one of the biggest concerns now. Coronaviruses (CoVs) are a group of related viruses that cause diseases in mammals and birds, which have an enveloped, crown-like (Latin: corona, meaning “crown” or “wreath”, as also seen in the corona of the sun) viral particle from which they were named after. They are viruses with a positive-sense single-stranded RNA genome and a proteinaceous coat and are classified into three groups. SARS coronaviruses belong to Group 2. We have already been introduced to SARS-CoV and MERS-CoV (Middle-East respiratory syndrome coronavirus), earlier in the twenty-first century [3]. However, SARS-CoV-2 is a bit novel with respect to them. SARS-CoV-2 enters the human cell via an interaction between a single region of the viral-spike protein called the receptor-binding domain (RBD) with the host-cell receptor, angiotensin I converting enzyme 2 (ACE2) receptor. A protease activity occurring at this point is necessary for the viral entry, but how and why that is the case is still unclear to scientists. Interestingly, SARS-CoV-2 recognizes human ACE2 more efficiently and binds to it more efficiently, compared to SARS-CoV, which had caused the SARS epidemic, which also originated in China in 2002 [4, 5]. This explains why SARS-CoV-2 has an increasing ability to transmit from person to person.

Does this virus kill everyone, or is it selective?

Now, while the virus attacks and kills cells in all cases, serious illness will depend on the extent of immune system response. This can be influenced by age, gender, genetics, and underlying medical conditions. The initial damage caused by the virus can trigger a powerful and counterproductive overreaction by the immune system itself, which can further add to more damage. It is important to have some conceptual basis of this, based on available scientific observations. This will help us to understand some globally observed facts and statistics.

ACE2 converts Angiotensin I (Ang I) to Ang 1-9. Ang 1-7 has several responses like anti-atrophy, anti-fibrosis, anti-inflammation, anti-oxidant, and vasodilation, which leads to tissue protection. ACE2 receptor is also found in many extrapulmonary tissues, including heart, kidney, endothelium, intestine, and mucosa of the oral cavity. This explains why SARS-CoV-2 is easily transmissible via droplets. Importantly, ACE2 is highly expressed on the luminal surface of intestinal epithelial cells, functioning as a co-receptor for nutrient uptake, in particular for amino acid resorption from food, which indicates that initial transmission of the virus from animal to human might be due to animal consumption from the wet markets in Wuhan, China. Also, as an expected protective response to viral infection, ACE2 receptor expression gets downregulated. Now, Ang I to Ang II and Ang III conversion is done by ACE, which is not the target of SARS-CoV-2. These products are responsible for the opposite activity and thus results in tissue damage. Understandably, tissue damage due to this and other factors is kind of balanced the ACE2 activity. Due to virally-induced downregulation of ACE2 receptors, this balance is affected, and tissue damage is the net result. This is probably why pulmonary symptoms are severe in COVID-19. Also, this tells us fatality is higher in people with additional underlying medical conditions related to heart, lung, and kidney [4, 6]. High probability of tissue damage and less efficient tissue repair in older people keeps them at a higher risk of fatality. Also, a high rate of additional alveolar epithelium damage explains why smokers are more vulnerable to SARS-CoV-2. Therefore, if you are a regular smoker, perhaps this is the best time to quit smoking.

Where do we stand and what’s next?

As mentioned before, coronaviruses are found in animals, and some of them, like, SARS-CoV-2, are zoonotic (transmits from animal to person). Since there is an animal reservoir, these viruses are hard to be eradicated. This makes finding a cure necessary. Scientists are trying their best to come up with a clinically available vaccine in the shortest possible time, and there has been significant progress in SARS-CoV-2 oriented-research, especially over the last three months. According to the latest reports, comparatively slower mutation rates in the virus have encouraged the development of a single vaccine against SARS-CoV-2. Also, a long term immunity seems to be achievable when the vaccine arrives in the market [7, 8, 9]. However, as of 25 March 2020, there is no fully reliable and scientifically established specific protocol against SARS-CoV-2. There are only some protocols which have shown some positive results, of which use of hydroxychloroquine and chloroquine the most popular[10, 11]. However, it still lacks substantial scientific backing. Common edibles like ginger, cloves, black pepper, turmeric, etc. have established anti-viral activity. However, while it is good to include these in our regular diet, there is no substantial evidence of their specific anti-viral activity against SARS-CoV-2 yet. While it is a good thing that, globally, researchers are on the right track to discover a SARSCoV-2 vaccine, we still need to give them some time to obtain a clinically available vaccine. Therefore, with some more time given, it can be said that the Coronavirus challenge is indeed a solvable challenge. To make this time as long as possible before we reach even more serious figures regarding the number of victims, social distancing, quitting smoking, and maintaining personal hygiene can be said to be the last resort.

References:

1. “Coronavirus Update (Live): 445,815 Cases and 19,768 Deaths from COVID-19 Virus Outbreak – Worldometer”.worldometer.com, Dadax, 25 March 2020.
2. Wee, S. & Wang, V. “China Grapples With Mystery Pneumonia-Like Illness”. The New York Times, Published: 6 January 2020, Updated: 21 January 2020.
3. Peiris, J.S.M in Medical Microbiology (Eighteenth Edition), Chapter 57: Coronaviruses, pg. 587-593, Elsevier (2012)
4. Zhang, H., Penninger, J.M., Li, Y. et al. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med (2020).
5. Wan, Y., Shang, J., Graham, R., Baric, R.S., & Li, F. Receptor Recognition by the Novel Coronavirus from Wuhan: An Analysis Based on Decade-Long Structural Studies of SARS Coronavirus. Journal of Virology Mar, 94 (7) e00127-20(2020).
6. Xu, H., Zhong, L., Deng, J. et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci 12, 8 (2020).
7. Tang, X., et al. On the origin and continuing evolution of SARS-CoV-2, National Science Review, nwaa036 (2020).
8. Grubaugh, N.D., Petrone, M.E. & Holmes, E.C. We shouldn’t worry when a virus mutates during disease outbreaks. Nat Microbiol 5, 529–530 (2020).
9. Achenbach, J. “The coronavirus isn’t mutating quickly, suggesting a vaccine would offer lasting protection”. The Washington Post, 25 March 2020.
10. Vincent, M.J., Bergeron, E., Benjannet, S. et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J 2, 69 (2005).
11. Wang, M., Cao, R., Zhang, L. et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 30, 269–271 (2020).


By Diptatanu Das, Department of Biological Sciences, IISER Kolkata.

(Feature Image by Ishika Saha, MA 1st year, Jadavpur University)

Author: Das Diptatanu

Diptatanu is a fourth-year BS-MS student at IISER Kolkata and a KVPY fellow, majoring in biology, with a chemistry minor. He has been a part of the gold-medalist iGEM IISER Kolkata teams in 2018 and 2019, and is also associated with next year’s team. Other than having a high affinity for good food and sleep, he loves to make music and play TT, football, cricket, etc., in his free time. He prefers to do some original work and has been writing articles, blogs and composing new songs. He is currently the CEO of IISER Kolkata Campus Radio and is also one of the admins and a regular blogger of our blog page, ‘The Qrius Rhino’.

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