Coronavirus mutations: which are important?

From G614 to RDRP, here's the changes in the virus that are worth knowing about.....
16 October 2020

Interview with 

Wesley Long, Houston Methodist Hospital

CORONAVIRUS_RNA

Black coronavirus particles and strings of RNA.

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Whenever the term 'mutation' gets mentioned in the context of the coronavirus, there’s usually confusion, because it sounds like it’s coming out of either a zombie movie or a Spiderman one. But the coronavirus - like all viruses - mutates all the time in tiny, often insignificant ways, whenever little parts of its genetic code get copied badly or otherwise change. We talked about this in a previous episode called the Coronavirus Mutation Situation. So the question is: among the flood of unimportant mutations, which ones are actually relevant or concerning? Phil sansom asked Wesley Long from Houston Methodist Hospital in Texas, one of many scientists tracking the virus as it spreads...

Wesley - The two genes that we've focused on the most, that many people are focused on: one is the spike protein, that's the large protein on the surface of the virus that, when you see the pictures of the viruses on the news, are the spikes that stick off of the coronavirus that really give it its name. And the other protein that we've been studying is a gene known as NSP12 or RDRP. That's really the protein that allows the virus to make copies of itself after it's infected a cell. And the reason we're really interested in both of those proteins is they affect treatments and therapies. The spike protein is particularly important for how the virus gains entry into cells; it's also the target of our immune system, our immune response; and then the RDRP is the site of action of antiviral drugs like remdesivir.

Phil - I guess then to figure out if these things are changing, you've got to track the virus over time. Where and when have you been looking at it?

Wesley - We've really been sequencing the virus now since March. So it's been about six months for us in Houston, in terms of having patients infected with COVID-19.

Phil - Over those six months, have you found anything important? Any big mutations?

Wesley - We have; we've found a wide variety of mutations. In particular there's one mutation, which has gotten a lot of press globally, in the spike protein; the resultant strains contain an allele that's often referred to as just G614, or "these are the G614 strains". They're really now the predominant strains in Europe and North America. And then we've found other mutations in the spike protein; and then also in the RDRP protein, some of which are concerning because they're near the active site for remdesivir. The possibility exists that the virus might be able to perhaps mutate to become more resistant to remdesivir or other antivirals.

Phil - Let's go back to the big change that you have seen then, which is this G614 you talked about. Describe what's happened there.

Wesley - It's just a single amino acid, this one single building block of that spike protein, that's changed. And for reasons that are still being investigated, it appears that that single change may have made it easier for the virus to infect host cells. There's still some debate about what the exact effect of the mutation is; however, the one thing that we can say is certainly in areas where this mutation has been found, strains with this mutation seem to become the predominant strains rather quickly over time. For instance in Houston, about 70% of the strains that we were seeing in early March had this G614 mutation. By the time we had our second wave, really June/July, essentially 99% of all the viruses that we were seeing were G614 mutation containing viruses.

Phil - Is that a one time thing, or is it likely that that might happen again?

Wesley - It is possible that it could happen again. It's another reason that we need to keep tracking the virus and sequencing it. It's also possible that there may be mutations that affect it negatively, that make it less fit. There is an example of a mutation that was found in Singapore in a different gene called ORF8, a rather large deletion of that gene, that appears to cause a virus that's much less severe. So the mutations can go either way in terms of changing viral behaviour, or increasing and decreasing severity. It's worth noting in our samples from Houston that although we have the G614 mutation, which seems to affect the ability of the virus to spread in populations, we didn't identify any mutations which affected outcomes in patients, positively or negatively.

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