Science

Strike at the spike and win the war

Spiky ball: This illustration provided by the Centers for Disease Control and Prevention (CDC) shows the 2019 novel coronavirus.

Spiky ball: This illustration provided by the Centers for Disease Control and Prevention (CDC) shows the 2019 novel coronavirus.   | Photo Credit: AP

The spikes made of a glycoprotein are the business end of the virus

During the last six weeks, a series of research papers have appeared that offer medical solutions to defeat the life-threatening coronavirus infection - COVID 19. These are apart from the attempts to produce a protective vaccine against it.

The picture of how the novel coronavirus (scientists also call it SARS-CoV-2) looks is by now familiar to all of us (see the picture above). It is a roundish ball with spikes covering its entire body. These spikes, which are the business end of the virus, are made up of a glycoprotein, and the detailed structure of the spike protein and how it helps in entering the host (what an unwelcome name! but scientists are polite people) cell of the infected individual is seen by a Seattle-based group, using cryo-electron microscopy (https://doi.org/2020.02.19.956851,) and also in the journal Cell < cell.doi.10.1016/j.cell.2020.02.058>. The spike protein recognises a specific enzyme called ACE2 on the cell surface, kills its activity and enters the host cell, and wreaks damage.

Learn from the past

Go back in literature, and one finds that this activity of the novel coronavirus is actually a historical one. People have studied the catastrophe caused in 1918 by the Spanish Flu pandemic, wherein millions died. The patients suffered severe lung damage, pneumonia, and acute respiratory syndrome, which has recently been seen again in severe acute respiratory syndrome (SARS) by the pathogen named SARS (called SARS-CoV coronary virus). Research here showed that the enzyme called Angiotensin Converting Enzyme or ACE2 fights against the viral attack and protects against damage (see; “good ACE, bad ACE do battle in lung injury, SARS” https://doi.org/10.1038/nm0805-821, and also that ACE2 is beneficial for hypertension, diabetes and cardiovascular diseases (Tikellis C, Thomas MC. Angiotensin-Converting Enzyme 2 (ACE2) Is a Key Modulator of the Renin Angiotensin System in Health and Disease., International Journal of Peptide Research 2012, doi:10.1155/2012/256294).

Hence this repeated request by public health officials to senior citizens across the world, and to those with these problems to stay safe at home.

Molecular and genetic basis

Most recently, a very important paper appeared from the Wuhan-based CAS lab for special pathogens, which revealed the genetic sequence of the novel coronavirus, its entry through deactivating ACE2 of the affected individual, plus another important point, namely, treatment of the affected by using the serum of a recently recovered patient. (This is important since it was shown as early as in 2006 by Liu and coworkers, < https://doi.org/10.1086/500469> when the SARS infected the world, treating the affected with the sera of recovered patients offered them the protective antibody IgG.). Hence the suggestion made across the world by some scientists that this can be followed in the present instance of COVID 19, too.

About the same time that this Wuhan work came about, comes another paper in the journal Cell from Leibniz, Germany (https://doi.org/10.1016.j.cel.2020.02.052), where the group confirmed that the novel coronavirus’ cell entry depends not only of ACE2 but another molecule (and enzyme) in the host cell, called TMPRSS2. They suggest further that the latter can be blocked by a clinically proven protease inhibitor! This is an important advance, since we may now look for such blocking molecules as drugs against the dreaded enemy the novel coronavirus SARS-CoV-2!

Take Home Lessons

We thus see four different ways of overcoming the enemy. The very first is what people must do (use protective devices and methods, do not allow community spread, stay home and safe); the second is to attempt to use the serum from recovered patients to boost the immunity of the afflicted; the third is to look for drugs to treat the affected and the fourth is to devise successful vaccines. These take time — but hopefully in months and not in years. Let us therefore attempt all of these methods.

A few words about SARS-CoV-2 and COVID 19. Two days ago, the newspaper The Guardian of U.K. points out that as many as 35 companies worldwide are racing towards such a vaccine, and at least 4 of them have tested their products on animals. Some have repurposed and modified their earlier vaccines against SARS and MERS to try on COVID 19. And two companies are building vaccines based on the messenger RNA that COVID19 has. But clinical trials on humans will take time to check on their efficacies and side effects, which may be as long as a year or more. Let us therefore attempt all of these methods.

We know by experience that where there is distress, there is hope; where there is hope, there are efforts; where there are efforts, there are solutions; and where there are solutions, there is success.

dbala@lvpei.org

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Printable version | Jun 5, 2020 1:25:20 PM | https://www.thehindu.com/sci-tech/science/strike-at-the-spike-and-win-the-war/article31192763.ece

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