The novel coronavirus is mutating – Should we be worried?

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Simran Kapoor addresses emerging fears about the novel coronavirus mutating.

As the novel coronavirus SARS-CoV-2 continues to spread around the world, there’s been a surge in news reports circulating with headlines about the virus mutating. The mere mention of the word “mutation” often elicits fear and confusion. Will this virus mutate into a more lethal strain which could threaten the human population? Will we ever be able to design a vaccine for this mutating virus?

Scientists who have been tracking the genetic sequences of the coronavirus as it spreads, are not surprised by variations in the viral genetic sequences and expect more genetic changes to arise. This is because mutations are a normal part of the virus life cycle. 

What exactly is a “mutation”?

The coronavirus, like any other virus, consists of a protein coat which encapsulates the viral genome which in turn determines the virus’s characteristics, from its structure to its functions. The virus stores this genetic information as a string of building blocks called nucleotides. Nucleotide sequences act as a genetic coding language by arranging into triplets called codons, where each codon represents an amino acid. Therefore, a sequence of nucleotides encodes a sequence of amino acids that in turn makes up a viral protein. When a virus infects a host cell, it has to replicate its genome to produce more copies of itself to spread further, but this process is rarely perfect. SARS-CoV-2 has around 30,000 nucleotides and it is only a matter of chance for a change to arise in any one of these nucleotides due to viral replication errors. It is these changes and errors that are scientifically termed as mutations.

What could these mutations mean for the course of this pandemic? 

Given the rates at which viruses replicate, a number of mutations could inevitably carry over to future copies of the virus. Movies like ‘The Contagion’ give the impression that mutating viruses typically become increasingly lethal. Fortunately, the reality is far from science fiction. 

More often, these mutations don’t change any traits of the virus due to the redundancy of the genetic code. This means that some codons, despite being different, still encode the same amino acid. Mutations could also generate a codon that encodes a similar amino acid, such that the properties of the protein do not change. Other genetic changes that occur may actually be detrimental to the virus, by changing its proteins in such a way that it becomes dysfunctional. Such viruses quickly get wiped out and disappear. 

So far, most mutations identified in SARS-CoV-2 have not been shown to change the virus significantly. But there are some mutations that could arise with the potential to enhance the transmissibility and infectiousness of the virus. For example, SARS-CoV-2 may benefit from a mutation that could block parts of our immune response, change its surface proteins to hide from the immune system or enable the virus to bind more strongly to human cells for increased transmissibility. A group of scientists at Los Alamos National Laboratory have made headlines recently for identifying one such mutation in the “spike” protein, the major surface protein used by the virus to attach and infect host cells. This lineage of SARS-CoV-2, called the G-lineage, evolved from the original D-lineage virus in Wuhan, China and has become increasingly dominant in Europe, North America, and Australia. The research group suggested that this may be a consequence of the mutation which might have enhanced the transmissibility of the virus, allowing it to outcompete the D-viruses in these regions. Whilst this is plausible, the dominance of G-lineage SARS-CoV-2 could also be explained by random chance. If the G-virus happened to infect someone travelling from China to Italy before the lockdown was initiated, it is highly probable that the virus could have subsequently spread across Europe, North America, and Australia. 

Movies like ‘The Contagion’ give the impression that mutating viruses typically become increasingly lethal. Fortunately, the reality is far from science fiction. 

The study has not yet been peer-reviewed and scientists urge caution on claims of new strains evolving as the word “strain” tends to be used very loosely. It’s easier to think of viral strains in terms of dog breeds. A white-haired chihuahua is functionally the same breed as a brown-haired chihuahua, despite differences in their appearance. Similarly, viruses may look different due to small mutations in their genome, but they are still the same strain if they don’t show significant functional differences from the original virus. Verification of these functional differences, however, is not an easy task, and requires strong data on animal models or humans before conclusions can be made.

The biggest fear emerging among the general public is that this virus will mutate in a deadly direction. But these fears should be put to rest, at least for now. The possibility of a more lethal strain of SARS-CoV-2 evolving seems unlikely in the near future of this pandemic. SARS-CoV-2 is not actually under much evolutionary selective pressure to change its form and function. The virus is cleverly doing well for itself as demonstrated by its successful replication and global spread so far. If the virus evolves to have a higher mortality rate, the mutation would be detrimental to its spread and the virus would quickly disappear. In fact, evolutionary biologists predict that this virus is likely to become less harmful in the coming years by co-evolving with humans. 

The flu shot has to be updated every year due to mutations in the influenza virus. Is something similar expected with the vaccine for SARS-CoV-2?

Seasonal flu causing influenza is a good example of a typical RNA virus where the high frequency of mutations can be attributed to higher genetic instability of RNA compared to DNA. In short, this means that its replication is highly error prone. The notoriously slippery influenza viruses therefore have a powerful trick up their sleeves. They can acquire mutations at a very fast rate which alters its protein surface making immune memory against the virus extremely poor. 

SARS-CoV-2 is a coronavirus which despite being an RNA virus, has highly efficient and relatively error-free replication cycles due to its special proof-reading machinery. Unlike influenza, the coronavirus actively checks on mutations arising during replication and largely maintains the integrity of its genome. To compare, influenza mutates roughly four times faster than SARS-CoV-2. The number of mutations identified so far is indeed extremely low considering the number of people SARS-CoV-2 has passed through. 

Given the slow mutation rate, a vaccine should work against the “vast majority of circulating COVID-19 strains for the foreseeable mutations,” says Dr Mark Schleiss, an infectious disease specialist with the Institute for Molecular Virology at the University of Minnesota. This means that it should be possible to produce an effective vaccine for SARS-CoV-2 to provide lasting immunity, as has been previously demonstrated with vaccines for other slowly mutating viruses, such as the MMR (Measles, Mumps, and Rubella) vaccine.

The number of mutations identified so far is indeed extremely low considering the number of people SARS-CoV-2 has passed through. 

Bottom line, yes, the coronavirus is mutating but this is normal and unlikely to cause the sort of catastrophe described in science fiction. Even if some beneficial viral mutations  arise, the worst-case scenarios are more likely to include some breakthrough infections, and will not result in an uncontrolled outbreak. But the world can’t relax just yet. The virus is still likely to become increasingly dangerous over time, and not necessarily due to its mutation. “This is far from over.” says WHO’s COVID-19 technical lead Van Kerkhove. “These public health and social measures may need to be introduced again, and that may frustrate people, which is completely understandable. And that, in a sense, could make the virus more dangerous because people become complacent.” 

Written by Simran Kapoor and edited by Tara Gamble.

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