Virus evolution, SARS-CoV2 variants, and learning the Greek alphabet.

While there is some debate concerning whether or not a virus is a life form, certainly the pressures of natural selection impact the evolution of viruses as they do other organisms (Krupovic et al., 2018; Worobey, 2001). One difference between viruses and even the simplest bacteria is the speed at which viruses can evolve and mutate. An example often used is the well-studied bacteria S. Aureus, which causes MRSA. This bacterium has around 2.8 million nucleotide base pairs in its genome (Lakhundi & Zhang, 2018). Given a calculated mutation rate of 1010 per base, this quickly equates to 300 mutations within the bacteria population within a single day. Compare this to any of the better-understood viruses; for example, influenza, mutations occur even more rapidly, requiring seasonal vaccination against the most likely strains.

Mutations, variants, and strains.

???????????Whenever a virus or other replicable cell replicates, the resulting copy has differences in either RNA or DNA. These differences are known as mutations. In a high percentage of resulting replications, these changes neither affect the resulting replicant. On exceedingly rare occasions, the resulting copy is different enough to be more robust. When a high enough percentage of replication occurs that have a favorable DNA or RNA structure, the combining differences create a variant. For large organisms like elephants, lions, whales, or humans, these mutations may make no difference in the organism, or can be detrimental as in the case of some well-known inherited genetic disorders including cystic fibrosis, sickle cell anemia, Tay-Sachs disease, phenylketonuria, or color-blindness (Peng et al., 2019; Peng et al., 2018). It should be noted that these disorders are caused by the mutation of a single gene. All genetic mutation can be caused by a limited set of circumstances. The organism could change simply due to an error in copying. A frequently used analogy is that if you were transcribing an extremely complicated manuscript, you would eventually have errors. On rare occasions the error actually makes sense. In this regard, the next copy will keep the error. If the error or mutation makes the organism less adaptable to survive it will die. Another reason that organisms mutate is because they have to due to pressure from the environment. Giraffes evolved longer necks over time due to the increased competition for low-growing food, bacteria involved different enzymes to combat antibiotics, and viruses mutate to survive the hostile environment within cells.?

Generations

???????????The generation of any organism can be understood by the time between birth and the ability to replicate, also known as sexual maturity. The Blue Whale can replicate at about 7 years of age (Bedri?ana‐Romano et al., 2018), elephants at about 9 years (Zang et al., 2021), lions at about 11 years (Romig et al., 2017), and humans, around 15 years of age (Dobewall et al., 2017). By adding the age of sexual maturity and the length of gestation, you arrive at a number that will roughly translate to the first opportunity for genetic replication through offspring. Compare the maturity of a virus which is instantaneous, and you can see why viruses mutate and change so quickly. With the accumulation of mutations that are beneficial to the organism, in the case of virus, a variant is created. Once this new variant has a new capability, for example, some bacteria have developed the ability to survive antibiotics, they are said to be a new strain. This happens slowly for bacteria and is generally the result of the overuse of antibiotics. It happens so much faster for viruses if they are allowed to survive to mutate in an unprotected host cell.

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This understanding becomes of critical importance for those with compromised immune responses, for example, someone who is undergoing chemotherapy, or someone with an autoimmune disorder that is being treated with immunosuppressant drugs. If such a person is infected with Covid, even if they have been vaccinated, the virus may be able to fend off the antibodies, and as a result, may mutate. The use of a vaccine by less than 100% of the population can also help create more robust variance, therefore the greater number of people vaccinated, the less likely the chance of infection and mutation. Viruses, like any organism is evolving to survive. When people refuse to be vaccinated and are exposed to the virus, they are essentially volunteering to be a walking petri dish for viral evolution. When they shut the virus, it can go out into the community either as a unchanged virus or as a stronger and more robust virus; a variant.

The current variants of interest

???????????Unlike smallpox, which was made extend through vaccination, the level of vaccinated person has allowed the virus to not only thrive, but the opportunity to mutate into a more robust and in some cases more infectious variant. Currently, there are a growing number of variants that have become an increased threat.

???????????Eta variant was first identified in December 2020 in both the United Kingdom and Nigeria (World Health Organization, 2021). Etta has the potentiality to reduce the effectiveness of monoclonal antibody treatments currently under Emergency Use Authorization.

???????????Iota was first identified in New York in November 2020 and also has reduced susceptibility to monoclonal antibody treatment and a reduced effectiveness of convalescent serum.

???????????Kappa was first identified in India in December 2020 and has the potential to neutralize some monoclonal antibody treatment and post-vaccination serum as noted in the previous two variants.

Variants of elevated concern

???????????The attributes of a variant of concern or interest include having a negative impact on diagnostics, treatments, or available vaccinations, increased transmission rate, decreased susceptibility to available therapeutics, including increased disease severity.

???????????Delta was first identified in India, and is considered the current variant of concern because of the increased evidence in transmissibility, the likelihood of increased hospitalizations or deaths, the reduction in neutralization by antibodies resulting from infection or vaccination and a reduced effectiveness of vaccines (Alizon et al., 2021).

???????????Alpha was first identified in the United Kingdom and has a 50% increased transmission based on infection and hospitalization rates. Alpha currently shows minimal impact on utilization by therapeutic interventions.

???????????Beta was first identified in South Africa and has an identified 50% increase transmission rate, reduced susceptibility to some forms of monoclonal antibody treatment and reduced neutralization by post-vaccination or post-infection serum treatment (convalescent sera).

???????????Gamma was first identified in Brazil and Japan at approximately the same time. Gamma shows significantly reduced susceptibility to monoclonal antibody treatment and reduced neutralization by convalescent sera.

While each of these variants has a significant impact on medical countermeasures, the greatest threat to the spread of this pandemic and the increasing number of variants is the refusal by members of the population to become vaccinated. Eventually, given enough time to mutate into more virulent and transmissible variants, the resulting reduced susceptibility to currently approved therapeutics, more severe clinical disease, hospitalizations, and deaths will occur.

References

Alizon, S., Haim-Boukobza, S., Foulongne, V., Verdurme, L., Trombert-Paolantoni, S., ??Lecorche, E., ... & Sofonea, M. T. (2021). Rapid spread of the SARS-CoV-2 Delta ????variant in some French regions, June 2021. Eurosurveillance, 26(28), 2100573.

Bedri?ana‐Romano, L., Hucke‐Gaete, R., Viddi, F. A., Morales, J., Williams, R., Ashe, E., ... & Ruiz, J. (2018). Integrating multiple data sources for assessing blue whale abundance and ?????distribution in Chilean Northern Patagonia. Diversity and Distributions, 24(7), 991-????????1004.

Dobewall, H., Tormos, R., & Vauclair, C. M. (2017). Normative value change across the human life cycle: Similarities and differences across Europe. Journal of Adult Development, ???????24(4), 263-276.

Krupovic, M., Cvirkaite-Krupovic, V., Iranzo, J., Prangishvili, D., & Koonin, E. V. (2018). ????????Viruses of archaea: Structural, functional, environmental and evolutionary genomics. ?Virus research, 244, 181-193.

Lakhundi, S., & Zhang, K. (2018). Methicillin-resistant Staphylococcus aureus: molecular ?????????characterization, evolution, and epidemiology. Clinical microbiology reviews, 31(4), ??????????e00020-18.

Peng, Y., Alexov, E., & Basu, S. (2019). Structural perspective on revealing and altering molecular functions of genetic variants linked with diseases. International Journal of ????Molecular Sciences, 20(3), 548.

Peng, Y., Alexov, E., & Basu, S. (2018). Structural Perspective on Revealing and Altering ?????????Molecular Mechanisms of Genetic Variants Linked with Diseases.

Romig, T., Deplazes, P., Jenkins, D., Giraudoux, P., Massolo, A., Craig, P. S., ... & De La Rue, ?M. (2017). Ecology and life cycle patterns of Echinococcus species. Advances in ??parasitology, 95, 213-314.

World Health Organization (2021). Coronavirus. From https://www.who.int/health-?????????topics/coronavirus#tab=tab_1

Worobey, M. (2001). A novel approach to detecting and measuring recombination: new insights into evolution in viruses, bacteria, and mitochondria. Molecular Biology and Evolution, ????18(8), 1425-1434.

Zhang, X., Border, A., Goosen, N., & Thomsen, M. (2021). Environmental life cycle assessment of cascade valorisation strategies of South African macroalga Ecklonia maxima using ?green extraction technologies. Algal Research, 58, 102348.

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