{"id":3589,"date":"2020-08-14T15:08:21","date_gmt":"2020-08-14T15:08:21","guid":{"rendered":"https:\/\/www.editage.com\/insights\/the-role-of-science-and-scientists-in-mitigating-the-covid-19-pandemic-part-2\/"},"modified":"2025-01-15T06:29:45","modified_gmt":"2025-01-15T06:29:45","slug":"the-role-of-science-and-scientists-in-mitigating-the-covid-19-pandemic-part-2","status":"publish","type":"post","link":"https:\/\/www.editage.com\/insights\/the-role-of-science-and-scientists-in-mitigating-the-covid-19-pandemic-part-2","title":{"rendered":"The role of science and scientists in mitigating the COVID-19 pandemic (Part 2)"},"content":{"rendered":"

Note:\u00a0<\/i><\/b>This content was originally published on\u00a0IndiaBioscience<\/a>\u00a0on May 20, 2020, and has been republished here with permission.\u00a0<\/i><\/span><\/span><\/span><\/p>\n

As we gradually transition into the fourth phase of the nationwide lockdown, we continue to implement strong defensive strategies against the novel coronavirus, including fast and reliable diagnostic procedures, as well as plans that limit the spread of the contagion. However, to be effective, these must be combined with equivalent offensive tactics against the virus, such as drugs and vaccines.\u00a0<\/span><\/span><\/span><\/p>\n

This concerted\u00a0\u200b\u201cdefence\u00a0&\u00a0attack\u201d approach is necessary for eradicating this deadly pathogen. An effective and successful\u00a0\u200b\u201coffensive\u201d approach will ultimately depend on formulating and developing both prophylactic (preventive) as well as therapeutic (treatment) strategies to fight SARS-CoV\u20112. Such strategies can only be developed if we combine our scientific knowledge from previous viral infections with modern scientific and technological advancements.\u00a0<\/span><\/span><\/span><\/p>\n

In the first part of this article<\/a>, we discussed how understanding the novel coronavirus\u2019s biology helps us devise methods to restrict its spread and quickly diagnose its presence in patient samples. This second part will focus on the wealth of knowledge we have gained from previous such viral infections of pandemic proportion, and how some of these have been translated to SARS-CoV\u20112\u00a0research with an aim to discover novel therapeutics.<\/span><\/span><\/span><\/p>\n

Developing therapeutic strategies\u00a0<\/b><\/span><\/span><\/span><\/p>\n

The need of the hour is to develop drugs against this deadly virus \u2013 which is easier said than done. Before we come up with strategies to fight the virus, we need to study its behaviour closely to understand which of its essential processes we can target.\u00a0<\/span><\/span><\/span><\/p>\n

Currently, researchers are following three main approaches. The first approach is to find a\u00a0drug that can prevent the virus from entering the cell. However, for this, we need to understand exactly\u00a0how the virus enters<\/a>\u00a0the host cell. The second approach is understanding how the virus replicates inside the host cell and developing agents that could block this replication cycle. Finally, in the third approach, researchers are also investigating if drugs which are already approved and available commercially can be repurposed to target\u00a0COVID-19.<\/span><\/span><\/span><\/p>\n

Strategy\u00a01: Targeting SARS-CoV\u20112\u00a0binding to the host\u00a0cell<\/i><\/b><\/span><\/span><\/span><\/p>\n

A little over a\u00a0month after the first reported\u00a0COVID-19\u00a0case, a\u00a0group of researchers led by Jason McLellan from the University of Texas\u00a0published a\u00a0detailed structure<\/a>\u00a0of the viral\u00a0\u200b\u201cS\u201d protein (which forms its spiky outer layer) and highlighted how it is used by the virus to bind to the host cell. This study demonstrated that the virus uses a\u00a0\u200b\u201cLock and Key\u201d mechanism to attach itself to the host cell, which is the first step in the infection process.\u00a0<\/span><\/span><\/span><\/p>\n

In this, the viral\u00a0\u200b\u201cS\u201d protein acts as the\u00a0\u200b\u201cKey\u201d which attaches itself to a\u00a0human protein,\u00a0ACE2\u00a0(Angiotensin Converting Enzyme), which acts as a\u00a0\u200b\u201cLock\u201d.\u00a0ACE2\u00a0is present on several human cells including the cells that line our lungs. This attachment is essential for viral entry into the host cell, and therefore presents a\u00a0unique opportunity to scientists, as any molecule that can disrupt this attachment can be potential drug candidates.\u00a0<\/span><\/span><\/span><\/p>\n

Another study<\/a>, published at the beginning of March\u00a02020, provides more support to this approach. In this study, a\u00a0group of researchers from the Leibniz Institute for Primate Research, Germany, working under the leadership of Stefan Polhmann demonstrated that another protein,\u00a0TMPRSS2\u00a0assists in viral entry into the host cell by priming the spike protein\u00a0\u200b\u201cS\u201d. This study also highlights how a\u00a0synthetic inhibitor, Camostat Mesylate, can target this viral protein and blocks the virus from entering the host cells. This kind of breakthrough research opens up possibilities of new drug discovery which targets the virus-host attachment.<\/span><\/span><\/span><\/p>\n

Strategy\u00a02: Targeting SARS-CoV\u20112\u00a0replication inside the host\u00a0cell<\/i><\/b><\/span><\/span><\/span><\/p>\n

Researchers have also been trying to find ways to target viral replication\u2009\u2014\u2009the process through which the virus multiplies once it\u2019s inside the host cell. A\u00a0ground-breaking study by a\u00a0group led by Rolf Hilgenfeld at the University of Lubeck, Germany,\u00a0described the detailed structure\u00a0<\/a>of another viral protein, Mpro, which plays an integral role in viral replication. The researchers also showed that the reproduction of the virus inside the cells could be blocked by using an inhibitor, \u03b1\u2011ketoamide, thereby offering a\u00a0promising strategy for potential therapeutic intervention.\u00a0<\/span><\/span><\/span><\/p>\n

Strategy\u00a03: Repurposing already approved drugs<\/i><\/b><\/span><\/span><\/span><\/p>\n

Alternate strategies for treating\u00a0COVID-19\u00a0may stem out of repurposing drugs that are already in the market for other diseases and disorders. Already antiretrovirals, which have been used to treat\u00a0HIV\u00a0infections, are being explored for their efficacy against\u00a0COVID-19. However, these have had limited success, and the\u00a0findings from the trials<\/a>\u00a0have been\u00a0somewhat contradictory<\/a>. Very recently, a\u00a0laboratory study highlighting a\u00a0combination of Remdesivir, an antiviral drug, and chloroquine, a\u00a0common anti-malarial drug,\u00a0has shown great promise<\/a>\u00a0against SARS-CoV\u20112.<\/span><\/span><\/span><\/p>\n

Just recently, Remdesivir alone\u00a0has shown tremendous promise<\/a>\u00a0in a\u00a0group of patients with\u00a0COVID-19\u00a0and is presently under clinical trial, conducted by\u00a0GILEAD,\u00a0USA. These results were backed up\u00a0by another publication<\/a>\u00a0showing that hydroxychloroquine, a\u00a0derivative of chloroquine, can inhibit lab-grown SARS-CoV\u20112\u00a0with minimal toxicity.\u00a0Another drug combination<\/a>\u2009\u2014\u2009Azithromycin and Hydroxychloroquine\u2009\u2014\u2009has also been shown to show positive results on\u00a0COVID-19\u00a0infected patients in a\u00a0study by researchers at IHU-M\u00e9diterran\u00e9e Infection, Marseille, France, although these studies need further evaluation with larger groups of patients. An FDA-approved anti-parasitic drug,\u00a0Ivermectin has also been shown<\/a>\u00a0to have potent antiviral activity against SARS-CoV2. In another comprehensive study,\u00a0a\u00a0large scale screening<\/a>\u00a0of already available drugs identified\u00a030\u00a0potential drugs that could block viral replication.<\/span><\/span><\/span><\/p>\n

Alternate strategies<\/i><\/b><\/span><\/span><\/span><\/p>\n

As I\u00a0am writing this update, over\u00a04.9\u00a0million confirmed cases of\u00a0COVID-19\u00a0have been reported worldwide with more than\u00a03\u00a0lakh confirmed deaths. But researchers always try to find the little rays of hope within the grey, and the positive news here is that over\u00a01.9\u00a0million people have recovered worldwide. This means that all these people who have recovered are now harbouring priceless antibodies against this deadly virus in their bloodstream. Utilizing this anti-sera from people who have recovered from\u00a0COVID-19\u00a0may provide an excellent strategy to fight this infection.\u00a0<\/span><\/span><\/span><\/p>\n

In fact, during the\u00a0SARS\u00a0and the\u00a0MERS\u00a0pandemics a\u00a0few years back, sera with antibodies from recovered patients were used to successfully treat patients with an active infection. The\u00a0possibility of using such an approach<\/a>\u00a0for\u00a0COVID-19\u00a0has also been under discussion. Recently, a\u00a0purified but inactivated SARS-nCoV\u20112\u00a0virus\u00a0has been shown to be promising<\/a>\u00a0as a\u00a0vaccine candidate.<\/span><\/span><\/span><\/p>\n

An emerging idea in the treatment of\u00a0COVID-19\u00a0is to study human subjects who are naturally resistant to the virus. If we are able to identify subsets of people who are naturally resistant, comparative gene sequencing of such naturally resistant people with\u00a0COVID-19\u00a0susceptible patients may unravel a\u00a0treasure trove of data, which may assist in effective drug development against this virus. In fact, not long ago, studying people naturally resistant to the deadly virus\u00a0HIV\u00a0gave\u00a0us invaluable clues<\/a>\u00a0about their immunological profile,\u00a0<\/i>which played a\u00a0significant role in the development of anti-HIV treatment strategies.<\/span><\/span><\/span><\/p>\n

Indian initiatives on\u00a0COVID-19\u00a0research<\/b><\/span><\/span><\/span><\/p>\n

On the Indian side as well, initiatives on\u00a0COVID-19\u00a0research have been taken up quickly. While a\u00a0core team of professionals has been formed to formulate strategies to combat\u00a0COVID-19, the country\u2019s scientific organizations like\u00a0DST\u00a0have set up their own\u00a0COVID-19\u00a0task force to accelerate diagnostics and R&D to boost the country\u2019s effort to mitigate\u00a0COVID-19. Basic research\u00a0to understand the genomics<\/a>\u00a0of the virus infecting Indian population, as a\u00a0first step towards effective drug development,\u00a0has been reported<\/a>\u00a0in several pre-print publications.\u00a0DNA\u00a0sequence analysis of the S\u2011protein from Indian isolates has revealed\u00a0a\u00a0critical amino acid change<\/a>\u00a0in the viral S\u2011protein which might affect its infectivity in the Indian population. Similarly, Indian researchers\u00a0have been working<\/a>\u00a0on the\u00a0identification of potential<\/a>\u00a0drug targets and vaccine candidates\u00a0against SARS-CoV\u20112<\/a>.<\/span><\/span><\/span><\/p>\n

Past, present, and future<\/b><\/span><\/span><\/span><\/p>\n

Hope is not lost. In fact, what history has shown us is that the human race persists. Also, all this while, we have been thinking of the virus as a\u00a0constant entity without any change, but this is not true. As the virus infects more and more people, it encounters new micro-environments inside the human body and accumulates small changes. Evidence from both the\u00a0SARS\u00a0and Ebola epidemics has shown that with increasing infections and onward transmissions, the number of mutations in the virus\u2019s genome also increases.\u00a0<\/span><\/span><\/span><\/p>\n

Many of these mutations\u00a0do not affect the virus\u2019s pathogenicity<\/a>. Often\u00a0they reduce the harmfulness of the virus<\/a>, by reducing its infectivity or capacity to cause death. This is because a\u00a0virus cannot live by itself\u2009\u2014\u2009it needs a\u00a0viable host. Hence the virus always looks for environments where it can thrive, even if it comes at the cost of its ability to cause disease. In fact, the\u00a0Global Initiative on Viral Data Sharing<\/a>\u00a0has shown that SARS-CoV\u20112\u00a0genome has undergone mutations several times. Even the SARS-CoV\u20112\u00a0strain isolated from Kerala, India has undergone several mutations compared to the original Wuhan strain. Whether these mutations alter the virus\u2019s pathogenicity in the long term is yet to be studied.<\/span><\/span><\/span><\/p>\n

Finally, I\u00a0would like to end on a\u00a0slightly more philosophical note. Why are these outbreaks occurring at this particular period during human history? Do the increasing technological advancement of the human race and changing ecology\u00a0have anything to do with this<\/a>? Epidemiological data and genetic sequence analysis show that\u00a0many of these coronavirus strains might date<\/a>\u00a0as far back as ~\u00a05000BCE\u00a0or even earlier. Many of these originated in animal hosts, particularly bats. These viruses have\u00a0undergone mutations and exchanged hosts<\/a>\u00a0several times before transferring to humans. Are the changing climate, increasing pollution, and modernization in any way responsible for inducing critical mutations in these viruses, that enable them to be transferred to humans? Why are bats resistant to such viruses?\u00a0<\/span><\/span><\/span><\/p>\n

These questions prompt different perspectives, and hence alternate approaches to solve these mysteries. The answers to these questions might be critical in dealing more effectively with this kind of crisis. If anything, this global pandemic has paved the way to the inevitable realization that the development of a\u00a0supportive environment towards promoting scientific culture and temperament is essential towards tackling such pandemics in the future.\u00a0<\/span><\/span><\/span><\/p>\n

And towards meeting these ends, policymakers globally have to prioritize the promotion of a\u00a0better scientific environment and practice, both intellectually as well as financially. The most powerful message that has come out of all this is that the human race is capable of presenting a\u00a0united front against a\u00a0crisis, in spite of whatever geographical, racial, and religious borders may exist. With a\u00a0species so determined to persist, a\u00a0minuscule virus won\u2019t be able to defeat us so easily.<\/span><\/span><\/span><\/p>\n

Read part 1 of the article:\u00a0The role of science and scientists in mitigating the COVID-19 pandemic (Part 1)<\/span><\/span><\/span><\/a><\/p>\n

\u00a0<\/p>\n","protected":false},"excerpt":{"rendered":"

Note:\u00a0This content was originally published on\u00a0IndiaBioscience\u00a0on May 20, 2020, and has been republished here with permission.\u00a0 As we gradually transition into the fourth phase of the nationwide lockdown, we continue to implement strong defensive strategies against the novel coronavirus, including fast and reliable diagnostic procedures, as well as plans that limit the spread of the […]<\/p>\n","protected":false},"author":2189,"featured_media":33313,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"categories":[2445],"tags":[2711],"new_categories":[],"new_tags":[],"series":[],"class_list":["post-3589","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-covid-19","tag-covid-19"],"acf":[],"yoast_head":"\nThe role of science and scientists in mitigating the COVID-19 pandemic | Editage Insights<\/title>\n<meta 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