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A virus called Corona

Santanu Chakraborty | Updated on February 14, 2020 Published on February 14, 2020

See through: The coronaviruses are said to have spike proteins sticking out of their coats   -  ISTOCK.COM

Scientists are hoping to find a cure for respiratory illnesses by studying a virus’s mechanism of action — tracking it as it enters host cells and replicates inside them

What is life? One way of looking at this question is by asking what we consider as living beings. We could claim that a living organism is something that is capable of replicating itself, that is, giving birth to new copies of itself. By this way of looking at life, many things emerge as living — animals, plants and humans.

Then the simplest such organism is surely also the smallest, one made up of the least number of molecules? In this quest for the smallest replicating being, we could start at the level of single molecules and ask if there is any molecule that has the capacity to replicate itself. The short answer is no. The long answer is a story for another day.

Working up from here we can ask if a collection of a few molecules can find a way to reproduce itself. But first let us ponder a situation where, many millions of years ago, a few molecules capable of reproducing, but only when working in tandem, came together just by accident on the face of this Earth or deep inside its oceans. What would happen next is that, just by virtue of being able to replicate itself, this set of molecules — or form of life — would begin to take over the world. It could only be restrained by a competition for resources. The competition could come from another set of molecules — another life form competing for exactly the same molecules to build itself.

Two such groups of organisms arose millions of years ago on Earth, and they occasionally compete still: Bacteria and viruses. Viruses are the smaller of the two and can only replicate inside the cells of another living organism. In fact, they must hijack the machinery of another cell to reproduce themselves. This raises an interesting question. What arose first in evolution — the more complex organism or the simpler one that feeds off it?

How does a virus do it? Its first task is to enter the innards of a cell. Is a full entry required or will the insertion of only a part of the virus suffice? Different viruses have, over many millennia, evolved different strategies. In these strategies are contained the mysteries of their success and their virulence. It is the act of entering a cell that determines how infectious a virus is capable of being in its present avatar.

Cells — of bacteria, birds, pigs, dogs, humans and so on — are all contained inside an outer layer of molecules protecting the insides, much like the water inside a water-filled balloon is held in shape by the rubbery material of the balloon itself. The protective membranes of cells are made up of a multitude of molecules — fats, sugars and proteins — performing complex functions protecting the insides and regulating the entry and exit of myriad molecules. Numerous molecules stick outside of this membrane, sensing the flow of signals in the outside world. Some stick inside the cell to pass on messages. Many molecules do both.

To be successful a virus must find entry into a cell. Viruses have evolved molecules sticking out of their own surfaces that can dock on to the receptor molecules jutting out of cell membranes, to mediate entry inside animal cells. The more such receptors a virus can use to attach and enter, the more species it will be able to infect. From here on the virus proceeds to hijack its host cell into making many copies of itself.

Now copies are hard to make. Try making a copy of an object, any object, and you will see that the replica is never a perfect one. Now this fact is a most dangerous one when living cells in multicellular organisms such as humans try to replicate, for they must ensure that their DNA — wherein lies their code of life — is replicated as flawlessly as possible. The failure to do so can result in rogue cells that grow out of control at the cost of the entire organism’s health. Cancer is one such condition.

But such constraints do not hold in the case of unicellular organisms. Many viruses, in fact, have a replication machinery that is quite prone to error, leading to numerous variants within every replicant pool, each of which shall again multiply to produce many other variants. Such a swarm of viruses can quickly yield variants that have adapted to infect newer cell types in an altogether new species.

Coronaviruses are one such viral group that infect many different species. Particularly lethal variants emerge occasionally. The epidemics of SARS and MERS in the recent past were caused by coronaviruses. A new one has just raised its head and is spreading fast.

One of the unique things about coronaviruses is that they have so-called spike proteins sticking out of their coats, one part of which uses ubiquitous sugar molecules on the surfaces of most cells to infect them, and the other evolves very rapidly, ‘trying’ to find matches to protein receptors. Once such a match is found the virus can jump to infect a new cell type and, often, a new species. A third part of this spike protein then fuses the virus through the cell membrane. In fact, the presence of multiple species of animals packed in close quarters in farms, breeding centres for industrial-scale production of meat as well as local markets, likely allows the virus to repeatedly migrate between species, continuously acquiring new genetic variations before moving on.

No cure is known for the respiratory illness caused by the coronaviruses, but an understanding of its mechanism of action, from entering host cells to replicating successfully inside them, is being used by scientists to try and find a cure to this and other viruses. We can imagine the form of such cures despite the technical difficulties of achieving them. Specially designed small molecules could block the spike protein surfaces of the current coronavirus and render it incapable of infecting its human hosts. Or, perhaps, a molecule could block a key viral enzyme whilst having no effect on human molecules.

Until, of course, a mutant emerges, against which this particular drug is ineffective.

Such is the nature of a rapidly evolving viral storm. Even errors have their uses. Such is life.

Santanu Chakraborty   -  BUSINESS LINE

 

Santanu Chakraborty is a Bengaluru-based engineer, scientist and photographer

Published on February 14, 2020

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