Ask a Molecular Biologist: How Do You Make Sense of Emerging COVID-19 Variants?

COVID variant Q&A

Verywell / Mira Norian

With so many letters and numbers being thrown around, it can feel like we’re swimming in a COVID-19 “variant soup.”

With each new variant comes new questions. Could this variant take over? Will it cause more severe disease? Could it slip past our immune defenses and thwart our antiviral treatments? Finding the answers to these questions often involve carefully mapping the virus’s genome and studying how the virus behaves in cells in a lab.

Verywell spoke with Nevan Krogan, PhD, a professor of cellular molecular pharmacology and director of the Quantitative Biosciences Institute at the University of California San Francisco. Krogan’s lab studies how slight changes in genetics and protein structures can influence disease outcomes.

He explained that for all the COVID-19 variants that make the headlines, there are many others that don’t. In addition to studying the bigwig variants, like Delta and Omicron, scientists have gathered information about how each tweak in genes and proteins can change the behavior of the virus. When a new variant arises, they can use what they’ve learned to predict just how much trouble it will be.

This interview has been edited and condensed for clarity

Verywell Health: There are so many variants that circulate the world. How do you decide which ones to study?

Krogan: There are epidemiologists who monitor variants that are becoming more prevalent. There are a couple of variants that have come on board that are 10% prevalent in certain places. At that point, they could then overtake the present variant.

We look at entire viruses as they come online, and we can start to infect cells and look at what effects they’re having on the host.

But then we also look at specific mutations across many, many, many different variants, most of which are actually not that prevalent. Is there a mutation that seemingly is prevalent in a bunch of different variants? Maybe these variants themselves aren’t prevalent, but there’s a particular mutation in a gene that could then become more problematic in the future.

Verywell Health: How do you study these genetic differences?

Krogan: Mutations are driving increased transmissibility and the ability of the virus to overcome preventative measures, like vaccines, or treatments like Paxlovid. Understanding why these mutations are coming up and why they are potentially beneficial for the virus could be informative in terms of how it could overcome prevention measures and treatments that we have.

We can also look at the individual proteins and get a structure of them using a high-powered microscope. Is it disrupting its function? How is it disrupting this function?

You can study these viruses in their totality, but then you can isolate the individual mutations in the individual proteins and study them in greater detail. It’s like a puzzle. Each one of these is a different piece of data, and it’s about putting all the pieces together to give us kind of a whole view of what’s happening.

It’s like an arms race between us and the virus. More information about the virus puts us in a better position to put mutations in context.

What Is Spike Protein?

Spike protein is a large protein that makes up the crown-like exterior of the COVID-19 virus. The spikes work like keys that lock into a port, called the ACE2 receptor, to enter human cells. Once inside, they can manipulate the cells and replicate into lots of new viruses to further infect the body.

The COVID-19 vaccines and treatments target the spike protein to neutralize the virus before it infects cells.

Verywell Health: Apart from the spike protein, what are the other parts of the virus that are important?

Krogan: There are approximately 30 proteins in SARS-CoV-2. Spike is really important because it’s the protein that binds to the receptor ACE2 and injects all the viral material into our cells. But there are other proteins that are required to kind of replicate the virus in our cells.

After the virus has already infected our cells, it can start to mutate to suppress our immune response. Our cells want to turn our immune response on to fight off infection. If the virus, at least for a time, can avoid that tripwire being tripped, it can replicate more. We saw that with Alpha and then we saw it with Beta and Gamma.

BA.1—the first Omicron—could infect our cells but the virus couldn’t suppress our immune response. Then it mutated from BA.1 to BA.4 and BA.5 to be able to suppress our immune response much better due to mutations in genes outside of spike.

Vaccines are working great, but we need drugs. How do we get drugs? By figuring out what these other viral proteins are doing. We don’t know what the best targets are. The sad part is even though we think we know so much about this virus, we’re really just scratching the surface of the information that we can ultimately extract about it.

It would be great, ultimately, to have an entire map of all these 30 genes to know exactly what they do, and then if a mutation pops up, you can kind of be much more predictive of what that mutation is doing, not just in spike, but in many other genes as well.

Common Terms Related to COVID-19 Variants

When a new variant arises, we hear a lot about its “doubling time” and “growth advantage.” These terms often refer to the results of tests done to isolated human cells in a laboratory.

Scientists can study how quickly one variant replicates compared to another. But certain factors, like population immunity and which parts of the body the virus most commonly infects, can influence just how transmissible the variant will be in the real world. A virus can be more transmissible, Krogan said, but not replicate as well within our cells.

Omicron, for instance, was more transmissible than Delta because of mutations in its spike protein. But it wasn't as deadly as Delta because it couldn't replicate as well.

Verywell Health: What is the value of studying variants like Alpha and Beta that aren’t around anymore?

Krogan: The mutations in the earlier variants are going to rear their heads again. So I think it’s important to study all these variants, even if they’ve gone away, because certain aspects of them are going to come back.

It’s so important to be laying a foundation of knowledge across these different SARS-CoV-2 proteins, so that when a new mutation pops up within a new variant, we can leverage the information we already have.

We have so much more data to look at. We’re getting better and better at predicting.

Verywell Health: What should we know about the currently emerging variants, like BQ.1 and BF.7?

Krogan: It’s easy to jump to conclusions and become scared. But based on our previous experiences, vaccines work pretty well at whatever the virus has thrown at us. I think it would take a lot in order for this virus to mutate to a point where it becomes as problematic as it was before.

Nonetheless, it’s not like we should let up our guard.

Verywell Health: How has our ability to study these variants improved throughout the pandemic?

Krogan: It’s a tragedy. It’s a lot of pain and suffering. A lot of people have died. But because of the pandemic and because the scientific community has come together in such an effective way, we’re going to be closer to treatments and other diseases like cancer and neurodegenerative diseases.

The scientific community has come together in an unprecedented way. We have vaccines, we have treatments and more treatments are on the way. We did that in a couple of years. And the question is why isn’t the scientific community working like that on all diseases?

The challenge for us is to stay collaborative so that we can tackle other pandemics that will come down the pike in the future, but then also breast cancer, Alzheimer’s, heart disease, etc.

Verywell Health: How much does the average person really need to know about emerging variants? Where do we toe the line between fear-mongering and sharing important information?

Krogan: On one hand, it’s great to see, the nonscientific community engaged in science. You see scientists on the front page of newspapers instead of baseball players. You see the New York Times publishing the structures of proteins. Could you imagine that before the pandemic?

All that is good. But there’s a danger to it, in my opinion, as well. People start to jump to conclusions with a little bit of information. They think they’re experts now based on what they read on Twitter: “Here’s the doomsday virus has mutated” and all this. It’s good to educate the public on what’s happening, but it’s also a double-edged sword. Listen to the experts and don’t jump to conclusions. Don’t go on Twitter and read somebody who has said something and then take it as gospel.

What This Means For You

Throughout the pandemic, some COVID-19 variants have become better at evading our immune defenses than others. But a slew of research shows that the vaccines, and now the updated boosters, are the most effective tools we have to protect against serious illness and death from all variants.

The information in this article is current as of the date listed, which means newer information may be available when you read this. For the most recent updates on COVID-19, visit our coronavirus news page.

By Claire Bugos
Claire Bugos is a health and science reporter and writer and a 2020 National Association of Science Writers travel fellow.