The COVID-19 Pandemic is still a large part of our lives. At least, here, in Melbourne (and Victoria) at large, where Stage 4 Restrictions still being enforced. All of us have been waiting for that solace from the various drugs and vaccines that have been heralded in the news.

Just recently the AstraZeneca vaccine, one of the forefront and most promising efforts, has been put on hold after a reported case of an adverse reaction. This is not entirely comforting, but we have little reason to doubt its safety or efficacy yet. This is because such occurances are entirely common, even in prior vaccine Phase 3 trials.

However, this still calls in to question on what our insurance plan is when we are developing drugs and vaccine to tackle COVID-19. Are we entirely certain that a drug developed today will work tomorrow?

A illustrating example is that of HIV. We still don’t have a preventative vaccine (they are all stuck in Phase II), despite the fact that research has been continuously put forth since 1984.

While there are many reasons for not having a vaccine, but one simple explaination has to do with the rate at which the HIV virus mutates. It’s one of the fastest. Everytime we think we have a solution, it outruns it.

There has been much research and interest into mutations and pathogens recently.

Mutations are changes in the genetic code of an organism. They typically happen when replication or repair occurs.

One slightly comforting fact is the novel coronavirus is mutating relatively slowly at 2 new mutations per month.

Now, while most people think of X-Men mutants when they hear the word mutation, but far from it. Mutations, in most cases, are benign, that is they don’t change the organism’s power.

With that said, some do. But the tricky bit in genomics research is figuring out which mutations do and which don’t.

Mutations and SARS-CoV2?

Mutations such as the infamous D614G in Spike have caused media to go overboard. D614G, does according to recent reports increase viral transmission.

However, we don’t think this mutation will hamper current vaccine efforts. Antibodies will still recognize the Spike protein and kickstart an immune response to protect your body. At least according to current reports

Proteins are very complex things. Sometimes little mutations can have drastic effects. But what we know is that the function of a protein is completely determined by its structure.

But mutations can happen at any time. Certain mutations, for example, may stop a drug from capturing a protein. Our research and analysis showed that mutations in the Main Protease, where quite a few drugs target, may not be completely effective. This is because many mutations happen there, each of them slightly change the protein in slightly different ways.

This, is what is called drug resistance. If such mutations become more frequent, due to mismanaged outbreaks, then we are back to square one.

Why is this important?

Despite, already compelling reasons to ensure our drugs work over time. There is also another neat interpretation with mutations.

This has to do with the beauty of evolution. Mutations that happen in parts of the protein that are essential are usually lost. This is because nature selects for the one’s that are advantageous due to selective pressures.

They let us appreciate the evolutionary nature of the viruses. Although a slight caveat is the huge founders effects that we have seen with COVID-19.

A founder’s effect is when a mutation becomes frequent, not due to natural selection, but when it is first introduced into a new place. If say COVID-19 outbreaks happen in a place where there is little social distancing observed, they a certain mutation will become more frequent regardless whether it is advantageous or not. It’s just got lucky.

What can we do about it?

In order to stay a step ahead of the virus, we can try to figure out what mutations are present. And also try to simulate what mutations are possible. If this is done right, they we have an understanding of what might happen if a new mutation is spreading like wildfire and might not work with a certain drug.

Recently, our work in the Ascher lab was published in Nature Genetics

It features our online webserver, COVID-3D. COVID-3D looks at 120,000+ SARS-CoV-2 genomes (and also from SARS-CoV of SARS fame and Bat RaGT13) to look at what mutations are out there and what might potentially occur.

Through COVID-3D, we can see how important a mutation is, does it do anything to the protein, does it interfere with drugs and more.

To get a better understanding of how we did it, have a look at our Pursuit piece with A/Prof David Ascher, and Stephanie Portelli.