Experiments & Applications: S&T in Coronavirus Pandemic

Throughout the history of pandemics, technology has played its role in many ways in proliferating infectious diseases to a wider area. However, it’s the same science and technology (S&T) research and innovations that also provide a way out of such crisis for humanity. The underlying global order and inter-connectedness, as prevalent today, has reified the vulnerabilities for nations and a common global citizen. But the very order is allowing the global community to generate and share critical insights to deal with this pandemic collectively. Researchers are working endlessly to fight this “novel” virus which has hijacked our biological as well as physical well-being.

Rapid and persistent analyses are contributing to rapid decision-making at national levels to effectively mitigate the irrepressible virus. Epidemiologists are parallelly running models to be better informed and equipped against the lesser-known adversary. However, the models conceived at this stage are not meant to be snapshots of the future. They only describe a range of possibilities. And these possibilities would often traverse an exponential trajectory.¹ This discovered range of possibilities is negatively correlated to the time and experiments that allow us to update our knowledge of the virus.

Essentially, these models also need to use parameters to plug into the variables in the equations. The availability of experimental data from surveys and tests thus becomes essential for this task. Every model will contribute to the process of iterative refinement to lead us to a winning strategy. Simultaneously, robust tracking, testing and isolating is of immense value in the formulation of the successful model. And inevitably the only trusted path for slowing the spread of this infection, or to “flatten the curve”.

Microscopic Description of the Virus- Structure and Inherent Weaknesses

In order to understand the epidemiology of the disease, it is necessary to know the causative organism. The micro-organism- a virus, in this case, was first found in a 41-year old man who worked at a seafood market in Wuhan. By applying next-generation sequencing, scientists have identified genes for as many as 29 proteins, which carry out a range of jobs from making copies of the coronavirus to suppressing the body’s immune responses.² A Virus, unlike bacteria, must hijack living cells to replicate and spread in the host. Thus scientists are now looking for remedies to target the host instead of the virus. More specifically, it’s the identification of host dependency factors mediating virus infection will provide key insights into effective molecular targets for developing broadly acting antiviral therapeutics. ³

Notwithstanding some viruses that can quickly mutate and become resistant to anti-virals, SARS-CoV-2 does not seem to mutate that speedily. Thus it is possible to evolve a feasible treatment to be executed at a number of steps in the disease cycle.⁴ On the basis of structural studies and biochemical experiments, the genomic features of SARS-CoV-2 have been found to belong to the cluster of Betacoronaviruses that include SARS-CoV and MERS-CoV. The Coronaviridae family is a group of seven viruses which have crown-like (or corona in Latin) spikes of the virus protruding to the periphery, giving them their name.⁵ The typical features of this seventh member, namely SARS-CoV-2, in the family are listed below:-

1. SARS-CoV-2 “spike protein” has a high affinity to bind with a receptor ACE2 present in the human body (the same receptor used by SARS-1 to make an entry into the human body).⁶
2. Using a string of RNA, the virus recruits machinery inside the infected cell to read the RNA letters — a, c, g and u — and translate them into coronavirus proteins. However, the replication from this step onwards is complicated, since it involves a lot many proteins.⁷
3. Accessory Proteins: this is the unique feature of this virus. They help change the environment inside the infected cell to make it easier for the virus to replicate. Some of these mechanisms include blocking signals that the infected cell would send out to the immune system. Or by blocks some of the cell’s own virus-fighting proteins.⁸
4. Cytokine storm: This can be understood as a rapid and indiscriminate activation of the immune system by a viral disease. It is a common process that occurs when the cells come in contact with super antigens contained in a virus. However, it is still not clear at this stage if the virus is causing a cytokine storm because of superantigens or other unknown mechanisms. Reports of patients have suggested that the cytokine storm created by this disease is of a unique intensity and is also the cause of severe damage to the lungs, in a very short time.⁹
5. Limited detectable protein homology: homology modeling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV. But in the case of SARS-CoV, there was an incidence of early onset of symptoms due to attack of the lower respiratory tract. That has not been the case with SARS-CoV-2, where reports have shown mild upper respiratory tract symptoms. This suggests that while the former announced itself before it could spread, the latter is stealthier and spreads before it reveals itself.¹⁰
6. Based on the initial investigation, the following metrics have been estimated for understanding the spread of this virus. Basic reproductive number (R0), that is the expected number of secondary infections that one infected person generates on average in an entirely susceptible population is estimated at 2.2. ¹¹

Incubation period is the time between catching the virus and beginning to have symptoms of the disease. Most estimates of the incubation period for COVID-19 range from 1-14 days, most commonly around five days. ¹²

There exists a discrepancy in data, due to which the case fatality rate (cumulative current total deaths / current confirmed cases) cannot be estimated at this point. This is because the number of infected (and unmanifested) cases is still not known with the given methods of testing.

Search for Cure

So far, no clinically available antiviral drugs have been developed for SARS-CoV-2. Meanwhile the research community is seeking all the means to exploit what is now known or assumed about the common adversary that the world is fighting. Until a final cure or vaccination, reducing the effectiveness of the virus is the goal we are set towards.

Repurposing strategies: Some of the proposed responses against the virus can be compared with the countermeasures deployed to exploit an adversary’s communication setup. Using this analogy, some of the suggested measures can be understood as jamming, spoofing or intercepting the virus’ communication within the body.

Intercepting: This is an approach that aims to locally target the receiver or overwrite the signal that is being sent to the affected cells and disable the intended action. The idea is to develop a drug that can selectively kill the human cells which have gone haywire, that is, they are hijacked by the virus and its signals to the cells. The challenge here is to distinguish between infected and non-infected cells.¹³

Jamming: Inhibiting the spike-activation process by preventing the human enzymes to do so. The spike-activation requires the virus protein to get in touch with a human enzyme. These enzymes unwittingly come along and activate the spike protein. In a pilot study, researchers have proposed to stop this communication or the action by drugs like hydroxychloroquine itself. ¹⁴

Spoofing: The immune system makes proteins called antibodies to neutralize foreign proteins, such as those from a virus. Doctors are trying to infuse antibody-rich plasma from COVID-19 survivors into patients. Currently, research groups as well as biotech companies are also screening the survivor plasma to identify antibodies that can be manufactured en masse in a factory.¹⁵

Some of the studies are also scrutinising ways in which immunity can be boosted in a population without a Covid-specific vaccination. One major study in this regard, is the effect of Bacillus Calmette–Guérin(BCG) vaccine to boost human "frontline" immunity. It is the same vaccine that is used to immunise infants against tuberculosis for the last 80 years in developing countries. Trials are being carried out on health workers. The intent is to also to look at a correlation between BCG vaccine and fewer COVID-19 deaths in countries that have previously administered the vaccine.¹⁶

Technological Interventions

It has been agreed that digital technologies if used with care and precision can help largely in the mitigation and response strategy. Computers are being used to identify drugs and formulae to weaken the virus in ways as discussed above. Fleets of robots are being employed to rapidly disinfect public spaces. Artificial Intelligence (AI) and Machine Learning (ML) have only gained more popularity in the discourse of flattening the curve.

Biotechnology firms are making significant contributions in capturing and dealing with the situation.

Smartphone contact tracing is increasingly being recognised as a critical measure to direct and prioritise testing in the population. Countries like Taiwan, Singapore and Iceland have been exemplary at their efforts. Taiwan has successfully integrated this data with human intelligence to further strengthen their defence against the spread of this virus. In an unusual move, two giants of the tech industry- Google and Apple, announced a collaboration to build an update that will accelerate app-based contact tracing.¹⁷

For the purpose of testing and diagnosing people en masse, there is even a greater reliance on technology. Firms are taking up research to usher in methods that can overcome the limitations in the current system. Apart from the two main types of testing- Genetic and Serological, AI based systems are being developed to effectively reduce the time factor.¹⁸ Tools are being developed to support triaging in resource-constrained settings and high-prevalence areas.¹⁹

To address the pressing need for ventilators in some countries the large community of engineers has come together to exchange and build on their knowledge. Concurrently, big tech companies are pitching in to speed up the production to the required pace. 3-D printing is being predominantly employed to manufacture and meet these urgent needs. ²⁰

Lastly, technology has empowered the world population to tele-commute, while they face physical immobility. In the true sense of the word, “the consummerisation of IT”²¹ has gained its footing with the coming of this pandemic. Video-conferencing apps have truly been a means of balance constantly threatened by a virus.

Developments in Science & Technology, as they unfold in this pandemic continue our efforts towards the very definition of health system as given by WHO- “all the activities whose primary purpose is to promote, restore, or maintain health”.

Endnotes

1. "Coronavirus Models Aren't Supposed to Be Right - The Atlantic." 2 Apr. 2020, https://www.theatlantic.com/technology/archive/2020/04/coronavirus-models-arent-supposed-be-right/609271/ [3]. Accessed 16 Apr. 2020.
2. "Bad News Wrapped in Protein: Inside the ...." 3 Apr. 2020, https://www.nytimes.com/interactive/2020/04/03/science/coronavirus-genome-bad-news-wrapped-in-protein.html [4]. Accessed 16 Apr. 2020.
3. "The Best Hopes for a Coronavirus Drug - The Atlantic." 8 Apr. 2020, https://www.theatlantic.com/science/archive/2020/04/what-coronavirus-drug-will-look-like/609661/ [5]. Accessed 16 Apr. 2020.
4. Ibid
5. https://www.sciencedirect.com/science/article/pii/S092485792030100X?via%3Dihub [6], Accessed 14 Apr. 2020.
6. "The proximal origin of SARS-CoV-2 | Nature Medicine." 17 Mar. 2020, https://www.nature.com/articles/s41591-020-0820-9 [7]. Accessed 11 Apr. 2020.
7. "Bad News Wrapped in Protein: Inside the ...." 3 Apr. 2020, https://www.nytimes.com/interactive/2020/04/03/science/coronavirus-genome-bad-news-wrapped-in-protein.html [4]. Accessed 16 Apr. 2020.
8. Ibid
9. "The Best Hopes for a Coronavirus Drug - The Atlantic." 8 Apr. 2020, https://www.theatlantic.com/science/archive/2020/04/what-coronavirus-drug-will-look-like/609661/ [5]. Accessed 16 Apr. 2020.
10. "Coronavirus learned 'remarkable trick' making it far nastier ...." 6 Apr. 2020, https://www.express.co.uk/news/world/1265615/coronavirus-mutates-deadlier-sars-virus-pathogen-spread-China [8]. Accessed 12 Apr. 2020.
11. "Q&A on coronaviruses (COVID-19) - World ...." 8 Apr. 2020, https://www.who.int/news-room/q-a-detail/q-a-coronaviruses [9]. Accessed 16 Apr. 2020.
12. "Coronavirus Incubation Period (COVID-19) - Worldometer." https://www.worldometers.info/coronavirus/coronavirus-incubation-period/ [10]. Accessed 16 Apr. 2020.
13. "The Best Hopes for a Coronavirus Drug - The Atlantic." 8 Apr. 2020, https://www.theatlantic.com/science/archive/2020/04/what-coronavirus-drug-will-look-like/609661/ [5]. Accessed
    16 Apr. 2020.
14. "Hydroxychloroquine: What's Known About ... - The Atlantic." 6 Apr. 2020, https://www.theatlantic.com/health/archive/2020/04/hydroxychloroquine-trump/609547/ [11]. Accessed 16 Apr. 2020.
15. "The Best Hopes for a Coronavirus Drug - The Atlantic." 8 Apr. 2020, https://www.theatlantic.com/science/archive/2020/04/what-coronavirus-drug-will-look-like/609661/ [5]. Accessed 16 Apr. 2020.
16. "The BCG vaccine, used against TB, “could be detrimental” in ...." 10 Apr. 2020, https://caravanmagazine.in/health/bcg-vaccine-covid-immunity-caution [12]. Accessed 13 Apr. 2020.
17. "App-based contact tracing may help countries get out of ...." 16 Apr. 2020, https://www.economist.com/science-and-technology/2020/04/16/app-based-contact-tracing-may-help-countries-get-out-of-lockdown [13]. Accessed 16 Apr. 2020.
18. "Developing and deploying tests for SARS-CoV-2 is crucial." 19 Mar. 2020, https://www.economist.com/science-and-technology/2020/03/19/developing-and-deploying-tests-for-sars-cov-2-is-crucial [14]. Accessed 14 Apr. 2020.
19. "the AI Companies fighting COVID-19 Across The ... - BlockDelta." 13 Apr. 2020, https://blockdelta.io/the-ai-companies-fighting-covid-19/ [15]. Accessed 15 Apr. 2020.
20. "COVID-19 - How Tech is Helping - YouTube." 13 Apr. 2020, https://www.youtube.com/watch?v=KEG_sQrXtzE [16]. Accessed 15 Apr. 2020.
21. "Zoom's popularity has brought problems - The Economist." 8 Apr. 2020, https://www.economist.com/business/2020/04/08/zooms-popularity-has-brought-problems [17]. Accessed 16 Apr. 2020.

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