Understanding the evolution of pathogens is vital for establishing effective measures to prevent the spread of disease as well as to facilitate epidemiological understanding and enhance outbreak response.
In light of the coronavirus disease (COVID-19) outbreak, systems that can prevent disease transmission and surveil the spread of infectious pathogens have become a key focus of scientific research in the last two years.
Here, we discuss how data collected and analyzed via processing falling under the umbrella of bioinformatics is allowing us to track the evolution of pathogens, in particular, the evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus.
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Monitoring the adaptations of the SARS-CoV-2 virus
Researchers at the University of Illinois have traced the mutation rate of the proteome of the SARS-CoV-2 virus through time. In a paper published in the journal Evolutionary Bioinformatics in October 2020, the team at the University of Illinois describe how they began their tracking with the first SARS-CoV-2 genome that was published in January 2020, and continued with 15,300 genomes that became available several months later.
Their findings raise some concerns. Using bioinformatics, the collection and analysis of complex biological data such as genetic codes, the team highlighted regions of the genome that are still actively generating new mutations, signifying that the virus is still adapting. They also found that some regions of the genome are decreasing their rate of mutations, amalgamating around single versions of certain proteins.
These findings reveal that the virus is sharpening its mutational tactics and improving its success at replication and transmission, in contrast to the virus’s behavior in the initial phase of the breakout when it adopted a "whatever works" strategy to proliferate.
The regions that have demonstrated non-random variability have been deemed as proteins to monitor to understand how the virus is working to improve its transmission.
The 614 mutation
New mutations of the virus could jeopardize the efficacy of the vaccines that have already been developed and administered across the globe. Vaccines are developed to attach to specific shaped proteins of the virus, and so if the virus’s mutations amend the structure of these proteins then the vaccine may no longer be able to attach to the target it was designed to have an affinity with.
Using bioinformatics, scientists are monitoring which proteins and structures are being maintained and which are evolving, which is vital information for vaccine development as well as therapeutic development.
The team tracked the general slowing of the virus’s mutational rate from April, following an initial phase of rapid adaptation. From April, they observed stabilization within the spike protein in which they found that the amino acid at site 614 was replaced throughout the entire virus population during March and April. This is important because the spike protein attaches the virus to human cells.
The 614 mutation must have given the virus an advantage in helping it to increase its infectivity. Increased viral loads and infectivity have also been associated with the 614 mutation and some studies have linked it with higher fatality rates. Scientists believe that the mutation has this effect due to its role in mediating entry into host cells, thus facilitating the spread of the virus.
The scientists also noticed that two other notable proteins developed sites of stability also during April: the NSP12 polymerase protein; and the NSP13 helicase protein. The three mutations seem to be coordinated, while they appear in different molecules, they are following the same evolutionary process.
Additionally, through bioinformatics, the team identified areas of the virus proteome that, over time, are increasing in variability. This information can help scientists make predictions about how the course of the Covid-19 disease will change. Importantly, the identified increasing mutations within the nucleocapsid protein, which are responsible for viral release, replication, and virulence.
These regions that are rapidly evolving reflect the virus actively seeking ways to enhance its transmission. The two further proteins that have been highlighted are capable of interfering with the body’s natural response to viral infection, they block the beta-interferon pathway, a fundamental part of our antiviral defenses. Mutations in their proteins could be responsible for the uncontrolled immune responses that have been witnessed in patients hospitalized with COVID-19.
With scientists predicting that the SARS-CoV-2 virus will continue to be a global health problem for the foreseeable future, the use of bioinformatics to track the evolution of the virus will be vitally important to facilitating the development of new therapeutics to treat the disease it causes.
Additionally, this information will help us to develop more effective vaccines that can protect against all variations of the SARS-CoV-2 virus, which will become increasingly important if the virus continues to mutate and render earlier vaccines less effective.
Bioinformatics is being used by research teams across the world to keep track of the virus. This type of information will continue to be a key focus of research in terms of managing the COVID-19 pandemic as well as preventing the spread of future pandemic-potential pathogens.
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- Tomaszewski, T., DeVries, R., Dong, M., Bhatia, G., Norsworthy, M., Zheng, X. and Caetano-Anollés, G., 2020. New Pathways of Mutational Change in SARS-CoV-2 Proteomes Involve Regions of Intrinsic Disorder Important for Virus Replication and Release. Evolutionary Bioinformatics, 16, p.117693432096514. https://journals.sagepub.com/doi/10.1177/1176934320965149
- Wan, Y., Shang, J., Graham, R., Baric, R. and Li, F., 2020. Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus. Journal of Virology, 94(7). https://journals.asm.org/doi/10.1128/JVI.00127-20
- Wrapp, D., Wang, N., Corbett, K., Goldsmith, J., Hsieh, C., Abiona, O., Graham, B. and McLellan, J., 2020. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science, 367(6483), pp.1260-1263. https://www.science.org/doi/10.1126/science.abb2507