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Same virus, new variants

If you’ve done enough doom scrolling recently, you may have heard of new variants of the SARS-CoV-2 virus. While these variants bring with them mutations that may be cause for concern, there’s a lot of hype in the media about what these discoveries actually mean.

<strong>Dr. Efrem Lim</strong> is a virologist out of Arizona State University. The Lim Lab is interested in  interactions and evolution of the human virome. Courtesy ASU

To better understand what’s going on here, we spoke with virologist Dr. Efrem Lim from Arizona State University. He explained how these variants came to be, what they mean for the virus, and what we all need to do to stay safe.

Can you discuss how a virus mutates and why?

When the virus infects people and when they replicate, it make more copies of its genome. The nature of these virus proteins is that they’re error prone. When they replicate, the genomes are going to make mistakes. And that's not just coronaviruses, all viruses do that. 

So, as part of this natural replication, you're going to have a lot of genomes that are acquiring different mutations. It's sort of random. And the results are that if you were to sequence people, you're going to find all different mutations, or in this case variations.

But another thing is that not all of these mutations are beneficial and so some of them cause deletions in proteins. And if that protein is really required for infection, that means that a virus that has a mutation that loses that protein is a dead virus.

That's what we call selection, which is things that are important for the benefit of the virus, the advantages to the virus to grow and infect and cause disease. Those are the ones that you actually then see outside of that. 

One question though is what we scientists think about these mutations and if they actually matter functionally? Basically, do the mutations make the virus more deadly. For example, mutations can affect transmissibility of the virus or vaccine responses. 

We’re seeing multiple new variants of this virus (Brazil’s P.1, South Africa’s B.1.351, the UK’s B.1.1.7.) What can you tell us about these variants? 

Some of these reports are new interesting mutations that are one-offs here and there. Those we’re not so worried about. 

<strong>The UK</strong> is where we discovered the B.1.1.7. variant. At this point, the variant makes up a massive majority of the isolates circulating in the UK.

However, when we see mutations that are very common in a population – like say 30% of a population have this specific mutation –  the prevalence of these variants in the population is what becomes concerning. 

The UK variant, for example, is one that is pretty concerning. Because in the UK, about 80 to 90% of the circulating isolates are this specific B 1.1.7. So, it's a predominant strain, which means that if there's any selection for it being very beneficial and so forth, that might explain why this is such a dominant virus across the whole population. 

An article from the Atlantic says that the N501Y mutation may make the spike protein "stickier," allowing it to infect cells easier. Can you explain what this mutation is and why it's significant? 

The N501Y mutation represents the 501st position on the spike protein of the SARS coronavirus. The protein determines whether the virus can bind to the cell and enter it. So, that protein by itself has a big role in whether a cell can get infected or not. 

There are specific areas on the protein that determine the specific binding. We call that the receptor binding domain. This mutation in particular, the 501 mutation, is right within that region that specifically comes into contact with the ACE2 cell receptor

Therefore, any mutation on the exact site of contact could affect these kinds of functions related to infecting the cell, making it more sticky in that sense. That's where the data is suggesting that this could be a concern. 

<strong>At this point,</strong> most of us have seen this representation of the SARS-CoV-2 virus. But you may not know that those red structures jutting out from the virus' circular body are spike proteins. If our ACE2 receptors are the lock that lets the virus into our cells, the spike protein is the key.

Harvard has more new data since the Atlantic article that shows that maybe that's not so much a concern in terms of the vaccine responses. 

The study that has been done is that people took that wild-type virus – basically the normal SARS coronavirus – they made a single-point mutation to change that virus to the Y-variant mutation. (Editor's note: This is the "Y" in "N501Y", which stands for tyrosine. The tyrosine amino acid is replacing asparagine (N) at the 501st position on the spike protein's receptor binding domain.) And then what they did was they took serum from people who have been vaccinated by the Pfizer vaccine.

So, for people who have been vaccinated by the Pfizer vaccine, can the antibodies that are generated from the vaccine still neutralize the wild-type and the variant N501Y? The answer is yes. It blocks the virus at equal or similar levels. And that's a really good sign. That means that antibodies generated from Pfizer vaccines can still neutralize this new variant. 

Are any of these variants altering vaccine effectiveness right now?

In particular, that N501Y – this new data is showing that it probably does not have much of an effect. 

There are a couple of other mutations that similar studies have been done on and are showing some effects on how well antibodies can bind and recognize the virus. One of them is in the South Africa B.1.351 variant. If you're into those numbers, it's E484K mutation of the South Africa variant.

Another example in California,  there's a variant called the CAL.20C variant with a mutation called the L452R. This is also in a similar region of the spike protein where there is data that shows that it may affect antibody binding. 

So, on one hand, the good news is that the big thing everyone's concerned about, the N501Y in the UK, is likely not to have much of an effect. But then there are some that we should still keep monitoring and looking out for. 

This won’t be the last of the mutations, right? Discovering mutations will be a continual process as we learn more about the virus, correct?

Exactly. We should still expect to see mutations coming up. Maybe I can add one to that which is what's different from pre-January 2021 to post-January 2021 is that before that, the virus had been spreading in the population almost with free reign.

There were no vaccine responses, no antibodies. But now, as the world is getting vaccinated, that means that more people are going to have antibodies that can bind and recognize the virus. 

If there are mutations that evade the vaccine responses, those get selected for and may have a stronger selective pressure moving forward. 

In light of these new variants, what should we be doing to stay safe? Is there anything we should be doing differently? 

So, you're going expect to see mutations. What we should try to do on the public health side is keep up our surveillance. All we have to do is make sure that what we're one step ahead of the virus. 

If we know what is circulating, then we'll have data to answer ‘do these mutations actually escape the vaccine?’ And if so, we have enough time to then quickly update the other vaccines and prepare for that. 

It's not a very new concept, surprisingly, because some people seem to think that the SARS coronavirus is the only virus around. That's not true, obviously.

<strong>Virus surveillance techniques</strong> are used every year to track new mutations of the influenza virus. We can (and should) do the same thing for the novel coronavirus.

We've been doing similar things like this for influenza with the seasonal flu vaccine. The reason why we have to keep getting our new shots is because the viruses mutate over time. Naturally, every year, it's going to mutate and select for different mutations. 

We have in place a really good surveillance network for influenza, where every year in January or so we look at all the data; what's circulating around the world and what mutations could be a problem. 

Then, we update our vaccines so that by summer or by fall you have all these vaccines for the new strains that are ready to be distributed in a population. So that could still likewise function for the SARS coronavirus. All we have to do is make sure that we are keeping a lookup for these virions.

We should still be wearing masks and social distancing, right? 

Absolutely. 

When a person is infected, they're going to transmit it through respiratory aerosols. So, if you can block that by wearing a mask, then that's the best way you can protect others and yourself. 

For instance, say we end up getting a virus that has mutations that make it more sticky and transmissible. Well, if you wear a mask, the virus doesn't even get into your lungs and it doesn't matter if it's more sticky. 

So absolutely, we should all still wear a mask. 

It seems to me that you're obviously concerned about these variants, but you don't seem to be overly scared of them. Is that right?

That’s right. I mean, as I said, we expect to see mutations and many virologists are looking out for these things. And so far none of them are going to end humanity, for example.  Nothing that drastic. 

There are many things that we can still do to prevent them should something major arise. And we have all the tools to do that now that we have really good vaccines that are working and being distributed. It's actually really easy for us to then go back and update those. 

The hard part was actually getting the vaccines in the first place. I think we've turned a big corner with that.

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