No Cheers for Corona!
“Don't talk to anyone! Don't touch anyone!” - Dr. Erin Mears (starred by Kate Winslet), Contagion, 2011
“Social distancing” is perhaps the most common thing that people around the world - on television, newspapers, articles, blogs and social media platforms - are talking about right now. It rightfully seems to be the need of the hour, if we do not want to end up having numbers of victims as serious as the ones presented in the 2011 movie, Contagion, which is based on the rapid progress of a lethal airborne virus that kills within days.
Luckily for us, the virus that has been raging across the world since January 2020, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), previously known by the provisional name 2019 Novel Coronavirus (2019-nCoV), is not so deadly a virus as the one conceptualized in Contagion. However, if we decide to consider it as a “normal flu” and continue thinking ourselves to be invincible, we are wrongfully underestimating the whole scenario, and we might actually end up having millions of us falling as victims. Thus, while Contagion might not depict our case accurately, it surely gives us an essence of a serious viral outbreak and also gives us an idea about what could be waiting for us if we do not take our situation seriously now. Perhaps, this is why Warner Bros, who distributed the film, found that it is currently the second most in-demand film in its catalog, just behind the Harry Potter series . Therefore, we need to be worried, but not scared.
For a start, let’s try to understand what a coronavirus actually is, along with why and how one of its subtypes, SARS-CoV-2, has become one of the biggest concerns now.
Viruses are tiny particles (diameters going up to a few hundred nanometers, and length of maximum a 1000 nanometers), which have a component of genetic material, wrapped in an envelope made of proteins. Coronaviruses (CoVs) are a group of related RNA viruses in which, this envelope has , crown-like (Latin: corona, meaning "crown" or "wreath", as also seen in the corona of the sun) projections around the genetic material. Based on evolutionary and genetic differences, Coronaviruses are divided 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. However, SARS-CoV-2 is a bit novel with respect to them.
Coronaviruses ‘stick’ to animal cells using these crown-like projections, and are eventually engulfed into the cells via certain interactions that happen at that point of contact. In case of SARS-CoV-2 these interactions happen between a single region of the viral-spike protein called the receptor-binding domain (RBD) with a region on the surface of the animal cell, called the host-cell receptor - angiotensin I converting enzyme 2 (ACE2) . An enzymatic reaction occurring at this point, between the viral particle and the animal cell is necessary for the viral entry.
Interestingly, SARS-CoV-2 recognizes and binds to human cells more efficiently as compared to SARS-CoV, which had caused the SARS epidemic, that had also originated in China, back in 2002. This explains why SARS-CoV-2 has a relatively increased ability to transmit from one person to another. Also, the distribution of the ‘binding-region’ required for SARS-CoV-2, is such in human bodies - for example, it is present in the lining of our mouth - that it makes it easier for this particular virus to infect humans via transmission of droplets.
Now, while the virus attacks and kills cells in all cases, serious illness will also 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 add to further 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.
This ACE2 receptor, which the virus requires, to bind and eventually infect a human, are present in the intestinal lining of humans. So,the initial transmission of this virus from animal to humans may possibly be traced down to the variety of consumable animal products sold at the wet markets of Wuhan, China.
Now, this ACE2 also has certain roles to play in ensuring tissue repair and protection inside our bodies, like prevention of - atrophy (tissue degeneration), fibrosis (thickening and stiffening of tissue), oxidant generation (formation of ions inside the body which damage tissues), vasoconstriction (which increases blood pressure). But, as an expected protective response of our body to this kind of a viral infection, ACE2 receptor expression gets suppressed. This leads to lower activity of ACE2. Now, tissue repair in a victim’s body also becomes difficult. So, people with prior medical conditions are at a greater risk, because this viral infection may further aggravate their symptoms. This explains why fatality is higher in people with pre-existing medical conditions related to heart, lung, and kidney. Also, for the same reason, this might be the best time to quit smoking.
Another feature of SARS-CoV-2, like any other virus, is its ability to ‘mutate’. Mutation is an error in the genetic material of the virus, caused during replication i.e., when the virus is producing more of it’s kind.This may lead to the development of some aggressive strain, or a different strain altogether. However, the probability of development of a more aggressive strain has been found to be very low for SARS-CoV-2. Despite evidence of differences in the SARS-CoV-2 genome obtained from different patients globally, there is no need to be worried as of now. The mutations observed are minor and expected, and should not affect the development of a vaccine. Moreover, the latest reports claim that the mutation rate of SARS-CoV-2 is actually not as significant when compared to that of flu, and so, a single vaccine should be able to confer long term immunity as seen for measles or chickenpox. Even so, quarantine and social distancing are encouraged as these would decrease transmission rates, which would further reduce the probability of mutation of the virus as a whole and the chances of more humans getting infected.
There were rumours about SARS-CoV-2 originating in a laboratory, but they have now been declared false. The origin of this particular virus can be linked to this property of certain viruses which can make a jump from ‘infecting animals’ to ‘infecting humans’. They are called zoonotic viruses. SARS-CoV-2 is one such virus. Since an animal reservoir will always exist, even if all humans are declared free of this virus, it is hard to eradicate them. This makes finding a cure necessary.
Currently, there are four probable ways to tackle this virus, which are: a vaccine targeting the protein coat of the virus, a way to stop the reactions which promote viral entry into humans, blocking the ACE2 receptor which lets the virus bind to human cells, delivering excessive soluble form of ACE2 which binds to the virus, and eventually be eliminated as a complex, but does not let the virus bind to the cells. All of them have their advantages and disadvantages, but due to certain technical and/or practical limitations, a vaccine to treat COVID-19 is still not available in the market.
Scientists and doctors have now started venturing possibilities of an existing drug that might be effective against SARS-CoV-2. According to Zhang Xinmin, an official at China’s science and technology ministry, favipiravir, developed by a subsidiary of Fujifilm, had produced encouraging outcomes in clinical trials in Wuhan and Shenzhen involving 340 patients . This drug was also found to be effective against Ebola previously. In 2005, chloroquine was reported to be a potent inhibitor of SARS coronavirus infection and spread. Thus, chloroquine and hydroxychloroquine are being administered in various countries, including India. In fact, the Director-General, Indian Council for Medical Research (ICMR), has recommended empirical use of hydroxy-chloroquine for prophylaxis of SARS-CoV-2 infection on 22 March 2020. However, there is a lack of conclusive scientific research on this yet. Remdesivir – a failed Ebola drug, a combination of lopinavir and ritonavir – an anti-HIV drug combination, immunosuppressants like tocilizumab and sarilumab, and, blood pressure drugs, are some other remotely ventured options.
Common edibles like ginger, cloves, black pepper, turmeric, etc. have established antiviral activity. However, while it is good to include these in our regular diet, there is no substantial evidence of their specific antiviral activity against SARS-CoV-2 yet. It is evident that despite getting remote instances of protocols effective against COVID-19, no concretely established protocol could be developed yet, which is totally effective with solid scientific backing.
While it is a good thing that, globally, researchers are on the right track to discover a SARS-CoV-2 vaccine, we still need to give them some time to obtain a clinically available vaccine. To allow the researchers an appreciable amount of time without risking serious figures in the number of victims, social distancing, and personal hygiene are our only resort.
Lastly, it should be noted that it is humans who are responsible for bringing this global crisis upon ourselves. Alanna Shaikh, a senior international development consultant, and senior TED fellow,precisely summarized this while delivering her speech at TEDxSMU. According to her, “This is not the last major outbreak we're ever going to see. There's going to be more outbreaks, and there's going to be more epidemics. That's not a maybe; that's a given. And it's a result of the way that we, as human beings, are interacting with our planet. Human choices are driving us into a position where we're going to see more outbreaks. Part of that is about climate change and the way a warming climate makes the world more hospitable to viruses and bacteria. But it's also about the way we're pushing into the last wild spaces on our planet. When we burn and plow the Amazon rainforest so that we can have cheap land for ranching, when the last of the African bush gets converted into farms, when wild animals in China are hunted to extinction, human beings come into contact with wildlife populations that they've never come into contact with before, and those populations have new kinds of diseases: bacteria, viruses - stuff we're not ready for.”
Therefore, it is high time that we try to amend our actions, policies, and lifestyle because COVID-19 has again pointed to 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 has been increasing dangerously. It took 67 days for the total number of coronavirus victims to reach 1 lakh (from 31 December 2019, when COVID-19 was first reported in China), 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 globally, within only three days after crossing 3 lakh. As of last data that could be compiled here, the total number of COVID-19 cases stand out to be 519,899 (26 March 2020, 18:40 GMT) According to the World Health Organisation, all 195 countries in the world are affected. This should be a wake-up call for us; else, we might be too late.
Diptatanu is a third 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 this year's team. Other than having a high affinity for good food and sleep, he loves to do 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. Currently he is also associated with an online blogging page called 'The Qrius Rhino'.