SARS-CoV-2 Mutations: Friend or Foe?

The word “mutation” can elicit fear – perhaps due to the use of this world in the media, mainly in the sci-fi and horror industry, it has gained the connotation of a huge, scary change. Hence, the news of the virus responsible for COVID-19 mutating can be very alarming to the public – when the original virus is as bad as it is, should we fear some mutated super-killer version of SARS-CoV-2? What does it mean when a virus mutates?  

Simply put, mutations are changes in the genetic material. The genetic material of SARS-CoV-2 is an RNA molecule, consisting of about 30 000 nucleotides, which encode all 27 viral proteins¹. A mutation is a change to one of these nucleotides. Once the virus infects a cell, it starts to replicate its genetic material to make copies of itself, which can subsequently infect other cells. The process of replication is naturally prone to mistakes, which creates a mutation – RNA viruses, such as SARS-CoV-2, are known to be rapidly evolving, which could lead to the accumulation of mutations. The impact of mutations depends on their type and location.

Not all mutations that occur can spread through the population – when the change damages the ability of the virus to replicate, or has other detrimental effects on the structure, the mutations are removed by natural selection. On the other hand, the “silent” mutations – changes in the nucleotides that do not change the final protein product – have no effect on the functioning of the virus and spread very well.

Between these two extreme cases, there is a spectrum of mutations that to some extent change the characteristics of the virus. Mutations can make the virus more (or less) virulent, or affect its transmissibility. The latest research suggests that the D614G variant caused by the highly prevalent 23403A>G mutation in the European population increases human-to-human transmission and contributes to the rapidity of SARS-CoV-2 spread around the world².

Mutations can also lead to resistance to certain therapeutics. When a mutation occurs in the area where the therapeutic binds, it can affect this interaction and in doing so impede the inhibitory effect of the therapeutic. The 14408C>T mutation is adjacent to the predicted binding location of multiple therapeutics, including Remdesivir, Ribavirin, or Favipiravir, but the possible drug-resistance phenotype requires further assessment³. The aforementioned 23403A>G mutation could affect a domain important for antibody binding, resulting in potential vaccine mismatches, although its effect is not yet clear^2,4. Thus, it is vital that the variants of SARS-CoV-2, both the currently known and future ones, are monitored, studied, and carefully considered in the design of vaccine or other therapeutics.

Monitoring the mutations can help us trace the SARS-CoV-2 path around the world. Sequencing viral samples from patients with COVID-19 can track where and how the coronavirus is spreading in the population, and monitor its further changes⁵.

In the end, a mutation is simply an inevitable naturally occurring change in the genetic material of the virus. Are mutations dangerous for us? Some might be, but the more severe a mutation, the less likely it spreads widely, so there is no need to panic upon hearing about each new variant of SARS-CoV-2. Instead, the mutations need to be monitored and taken into consideration for therapeutic strategies.

References

1. Wu A, Peng Y, Huang B, et al. Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China. Cell Host Microbe. 2020;27(3):325-328. doi: 10.1016/j.chom.2020.02.001
2. Yurkovetskiy L, Pascal KE, Tompkins-Tinch C, et al.  SARS-CoV-2 Spike protein variant D614G increases infectivity and retains sensitivity to antibodies that target the receptor binding domain. bioRxiv 2020.07.04.187757; doi: https://doi.org/10.1101/2020.07.04.187757
3. Pachetti M, Marini B, Benedetti F, et al. Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant. Journal of Translational Medicine. 2020 Apr;18(1):179. DOI: 10.1186/s12967-020-02344-6
4. Koyama T, Weeraratne D, Snowdon JL, Parida L. Emergence of Drift Variants That May Affect COVID-19 Vaccine Development and Antibody Treatment. Pathogens. 2020;9(5):324. Published 2020 Apr 26. doi:10.3390/pathogens9050324
5. Genomic epidemiology of novel coronavirus: https://nextstrain.org/ncov/global