By Dr. Saumya Bhaduri

Why is the virus that causes Covid-19 so dangerous?

Imagine your city is attacked by a company of foot soldiers running and shooting with rifles.

Imagine your side is also armed with rifles and you successfully drive them off with few casualties. Now you hear another attack is coming. Only this time you see rushing toward your city an endless line of huge tanks. All you have are foot soldiers and rifles. This scenario is a good metaphor for what makes COVID-19 so dangerous. While previous viruses were also deadly, they were not as contagious nor did they cause as many concurrent symptoms as COVID-19.

If a tank here or a tank there gets through, we may find a way to render those few tanks harmless. But when a multitude of COVID-19 tanks invade our human bodies they take root, they get established. Once established they rapidly expand and more tanks overwhelm our defences. At that point, our bullets don’t work and we die.

That’s the worst-case scenario in the world so far approximately: 3.89 million deaths and 179 million confirmed cases. Okay, we only have (so far) an approximately ~2% chance of dying from COVID-19 (1).

Heck! We could be killed in our auto just going to the supermarket, so what’s the uproar!

The uproar is in the odds. To die in an auto accident is 1 in 107 auto accidents, not 1 or 2 per hundred (2). If jumping into a car for a quart of milk was a 1 in 100 chance of dying today, one would drink coffee black. One more consideration before the explanation of the science behind this particular virus: There have been over 179 million cases so far. Sure between 97-99.5% survive (1), but COVID-19 causes multiple adverse and multi-faced symptoms. Some are mild, some are severe, all the way up to those that come nose to nose with death. Most victims that experience serious reactions live the rest of their lives compromised, like those of us that already deal with compromised health issues, high blood pressure, heart issues, lung damage or more. Just remember, COVID-19 leaves you with complications you could have for the rest of your life.

What Makes This Virus So Deadly?

COVID-19 is a new virus affecting the human population all over the world. Since the human population is never exposed to this virus, the immune response does not trigger to produce antibodies right away to kill the virus. So, the virus multiplies rapidly to cause the infection. Also, the symptoms of the disease do not appear on the onset of infection. So, an infected person without knowing to transmit the virus to another person. Also, the transmission rapidly infects a large number of people due to globalization. At the beginning of this infection, there is no vaccine to prevent infection. This is why this virus become a pandemic traffic to the whole world. The following paragraphs briefly describe the biology of the virus.

Mechanism of COVID-19 propagation in human cell

This section explains how a human COVID-19 virus multiplies in the host cell. This virus needs a host cell, a living organism to propagate. The COVID-19 virus belongs to the coronavirus family. The name is derived from its crown-like structure as shown below in Figure 1.

Figure 1. Coronavirus COVID-19, as seen under an electron microscope. The spikes surround the virus, as shown in figure (3). These viruses are RNA (ribonucleic acid) viruses, where RNA serves both as the genetic material (genome) and the messenger RNA (mRNA) to code for viral proteins (4). The RNA and viral proteins are the building blocks of the virus (4). When COVID-19 infects humans, the glycoprotein (4,7) (present in the spike, as shown in Fig. 1) of the virus first attaches to the receptor site on the host cell (for example in this case the lung cell membrane). This viral protein present in the spike of the virus acts as a key to opening the door of the host cell allowing the virus to enter the cell (4-7). Once it enters the host cell the viral genetic material hijacks the infected cell, causing it to make more viral mRNA by a process called replication using a virus-encoded RNA-dependent RNA polymerase (RdRP; a biocatalyst called enzyme), which specifically replicates the viral RNA genome (4,5,7,8). The following diagram illustrates the structural components of the virus and explains the viral RNA replication. 

Figure 2. (A)The catalytic mechanism of RNA-dependent RNA polymerase (RdRP) in RNA replication (B) Illustration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that consists of four structural proteins and RNA genome. Adapted from reference 5.

This RNA-dependent RNA replication is a special process reserved exclusively for this RNA virus but not normal cellular RNAs (4,5,7). Now multiple copies of viral mRNA are able to make more viral proteins using the host cell’s machinery (4, 7; Fig. 2). Then the viral genetic material RNA, proteins, and spike protein assemble and are encapsulated with a membrane envelope from the host cell to produce new viruses. The newly synthesized matured virus comes out of the host cells and then enters neighboring cells where it again replicates (4). The process continues to build up to an infectious level which causes a specific disease in the host and continues to infect new hosts by transmission (4). This is a simple explanation of viral replication in a host.

Concluding remarks

Human civilization has never faced a crisis of such magnitude as that of the coronavirus COVID-19 pandemic infection in the last 100 years after the Spanish influenza pandemic in the year of 1918/1919. It is becoming more dangerous because of massive global travel. Also, this virus is new to humans which makes it more dangerous. COVID-19 has caused a pandemic because it is easily spread from person to person yielding a high rate of transmission and infectivity. This is a global issue. It is a global pandemic infection. It affects economics, individuals, countries, and the whole world. The people in poor countries are suffering severely. Instead of solving this pandemic infection and economic crisis as individual countries, we should work together to stop the sufferings of human beings. The newly developed vaccines will help to stop this pandemic but nevertheless, the world should be prepared to combat any future massive virus attack.

Precautions/Prevention against Covid-19 infection/transmission

Physical distancing, mask-wearing, wearing gloves, sanitizing hands, washing hands with soap, no mass gathering, ventilation, air purification with HEPA filter, and vaccine preparedness for new virus strains can protect us from future pandemics (9).

Acknowledgments

I thank Dr. Ranjit Dasgupta, Senior Scientist/Virologist, University of Madison-Wisconsin and Dr. Max Arens, Associate Professor of Pediatrics Co-Director, Retrovirus Lab Co-Director, Clinical Virology Lab Washington University School of Medicine, St Louis, Missouri for critical review of the manuscript. I thank Ms. Emily Rutland and Ms. Ishita Mitra for editorial review of the manuscript. I also thank my daughter Ms. Serena Bhaduri for encouragement to write the manuscript even if I became legally blind.

References

1.   COVID number of infections and deaths: WHO Coronavirus (COVID-19) Dashboard. World Health Organization.

https://covid19.who.int/. Accessed June 21, 2021.

2.   Odds of Dying: NSC Injury Facts. National Safety Council. https://injuryfacts.nsc.org/all-injuries/preventable-death

overview/odds-of-dying/. Accessed June 21, 2021.

3.   Eckert, A and Higgins, D, 2020. CDC, digital image, accessed 21 June 2021, https://phil.cdc.gov/Details.aspx?pid=23311

4.   Coronavirus biology and replication: implications for SARS-CoV-2. V’kovski, P., Kratzel, A., Steiner, S. et al. Nature Rev Microbiol

19, 155–170 (2021).

5.   RNA-Dependent RNA Polymerase as a Target for COVID-19 Drug Discovery

Wei Zhu, Catherine Z. Chen, Kirill Gorshkov, Miao Xu,Donald C. Lo, and Wei Zheng. SLAS Discovery 2020; Vol 25 (10), 1141-1151

6.   Viral glycoproteins: biological role and application in diagnosis. Banerjee N, Mukhopadhyay S. Virus disease. 2016

Mar;27(1):1-11. doi: 10.1007/s13337-015-0293-5. Epub 2016 Jan 18. PMID: 26925438; PMCID: PMC4758313.

7.   Viral capsids and envelopes: structure and function. Lucas, W. (2010). In eLS, (Ed.).

https://doi.org/10.1002/9780470015902.a0001091.pub2

8.   A structural view of SARS-Co-V-2 RNA replication machinery: RNA synthesis, proofreading and final capping.  Romano M,

Ruggiero A, Squeglia F, Maga G, Berisio R. Cells. 2020;9(5):1267. Cells. 2020;9(5):1267. Published 2020 May 20.

doi:10.3390/cells9051267

9.  CDC Guidelines: https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/prevention.html