Pirola (BA.2.86): The Silent Threat That Lurks Within Its Descendants
Be prepared for overnight horror as superspreaders could accelerate virus spread. Lessons from the past!
Pirola is a coronavirus variant that has recently caught the attention of virologists due to its high number of mutations. Although it is not currently a superspreader, Pirola belongs to the BA.2 lineage. Another sub-lineage, XBB, is causing concern in the health sector.
The super-mutated Pirola
Mutations in a virus can have a significant impact on its ability to infect humans or other hosts, and this is particularly true for the spike (S) protein and the receptor-binding domain (RBD) that interacts with human ACE2 receptors.
Pirola has 28 mutations in its S protein and 12 mutations in its RBD compared to its parental lineage BA.2, which is a significant number of mutations. Furthermore, Pirola has 33 new mutations in its S protein and 16 new mutations in its RBD compared to Kraken (XBB.1.5), which has been a superspreader for most of 2023.
However, despite accumulating mutations, Pirola has not surpassed the XBB descendants in terms of infectivity as of yet.
It is important to note that having several mutations does not necessarily mean that a virus has adapted or become more fit to survive. In fact, it might give the virus a disadvantage or less fit trait.
For example, some mutations may interfere with the virus’s ability to replicate or interact with the host’s cells. On the other hand, mutations may also confer new properties that allow the virus to evade the host’s immune system, which can make it more dangerous.
Evolutionary biologists have long studied how mutations can drive the evolution of microorganisms, including viruses. In the case of coronavirus, mutations can arise due to errors in the replication process, exposure to environmental factors, or interactions with other viruses.
Over time, some mutations may become fixed in the viral population, leading to the emergence of new variants. The emergence of new variants can pose a challenge for public health officials as it can complicate efforts to control the spread of the virus.
While Pirola has a high number of mutations, it has not yet become a significant threat to public health. However, its continued monitoring is necessary to assess its potential impact on the COVID-19 pandemic.
The case of Eris
The potential threat of Pirola is not one to be underestimated. Although it may not appear to pose an immediate danger, the danger lies within its descendants.
This phenomenon is not unprecedented in the world of evolutionary virology. The infamous superspreader Eris (EG.5) that made headlines in late July and early August 2023, serves as a prime example.
Initially, it was EG.5 that surpassed Kraken (XBB.1.5), which was then the most dominant lineage in most regions globally. However, as time went on, a descendant of EG.5, named EG.5.1 (still nicknamed Eris), began to surpass its parental lineage (XBB*), to the extent that, in late September 2023, it constituted more than 70% of sequences under EG.5* (EG.5 and its descendants).
The genetic makeup of the Eris descendant EG.5.1 is not substantially different from other XBB lineages that dominated most of 2023. It only involves a change of one or two mutations, or mathematically speaking, a `variable`. Thus, mathematical biologists and evolutionary virologists can easily predict the extent of damage that this can cause.
The ability of viruses to mutate and evolve rapidly makes them a constant threat to global health. The emergence of new virus variants with increased transmissibility, virulence, and resistance to current vaccines and therapies underscores the need for constant surveillance and proactive measures.
Understanding the genetic mechanisms that underlie viral evolution is crucial in identifying and controlling potential threats, such as Pirola and its descendants.
Pirola's similarity to Eris
Currently, there is a sub-lineage of Pirola (BA.2.86) that has been detected in most parts of the world, called BA.2.86.1. This sub-lineage has been rising in prevalence in the past week and has many mutations, which also means that there are many uncertainties or variables.
From an evolutionary perspective, mutation represents a key process through which heritable traits are generated and transmitted across generations, ultimately affecting the fitness of organisms.
In the case of SARS-CoV-2, mutations have been observed since the virus’s inception, and some of these mutations have been shown to affect the virus’s ability to infect humans and cause disease.
Although it is theoretically possible to predict how each mutation might affect the virus’s fitness or function, biological systems are not as simple as physical systems.
Mutations do not act in isolation; instead, they interact with other mutations and environmental factors, leading to complex and unpredictable outcomes.
BA.2.86.1 is a prime example of this complexity. While the sub-lineage has been rising in prevalence, it is not yet clear what the long-term consequences of its many mutations will be.
Some mutations may provide a selective advantage, increasing the virus’s fitness, while others may be deleterious, decreasing the virus’s fitness.
In the context of evolutionary biology, it is important to acknowledge that what happens in nature cannot be fully simulated. The fitness landscape is constantly changing, and environmental factors play a critical role in shaping the trajectory of evolution.
As such, predicting the future of BA.2.86.1 and other sub-lineages of SARS-CoV-2 requires a nuanced understanding of the underlying biology and an appreciation for the complexity of evolutionary processes.
The case of ancestral omicron and lessons from XBB*
The identification of a new viral variant is always a cause for concern, especially in the current global health crisis. With the emergence of the Omicron variant in November-December 2021, the world witnessed how quickly a new variant can spread and outcompete the existing variants.
The Omicron variant, which underwent saltational evolution, exhibited a significantly higher number of mutations than the previous variants, leading to increased immune evasion and the possibility of reduced vaccine efficacy.
One of the factors that contributed to the rapid spread of the Omicron variant was the lack of attention paid to it in the initial stages. With the Delta variant already causing significant harm, the detection of a new variant did not raise immediate alarms.
However, as the number of Omicron sequences identified increased, it became clear that this variant was spreading much faster than anticipated.
As with any viral variant, the possibility of further mutations leading to the emergence of sub-lineages is a significant concern. If these sub-lineages regain all the mutations that are advantageous to their proliferation, or a recombinant variant emerges, we could be looking at an overnight superspreader event.
The Omicron variant was challenging to neutralize with existing antibodies due to the significant structural changes in the S protein. The S protein is responsible for the entry of the virus into human cells, and any mutations in this protein can significantly impact the virus’s infectivity.
The mutations in the Omicron variant led to increased immune evasion, making it difficult for the existing antibodies to bind firmly.
Despite the widespread concern over the Omicron variant, several sub-lineages emerged in terms of global dominance. However, by the end of 2022, the XBB lineage started to dominate the Omicron sub-lineages race.
The weakness of XBB.1 was its inability to bind tightly to the human ACE2 receptor, leading to low infection rates. However, a single mutation (N501Y) enabled the XBB variant to regain its ability to fit tightly on the ACE2 receptor, leading to the rise of Kraken (XBB.1.5), the dominant variant for most of 2023.
In summary, the emergence of new viral variants is a constantly evolving situation that requires ongoing vigilance and research. The Omicron variant highlighted the need for rapid detection and response to new variants, as well as the importance of understanding the mechanisms that drive the emergence of sub-lineages and recombinant variants.
In conclusion
The past is a great teacher of the future, and there is much that we can learn about what is to come from the knowledge of what has already been. Evidence from the past has shown that Pirola is not a super-spreader, due to the accumulation of several mutations that are not as beneficial.
However, the real threat lies in its offspring, which may regain lost advantageous traits, such as tight fitness to the ACE2 receptor, leading to higher reproduction rates and transmissibility (similar to Kraken).
Moreover, the change in S protein structure shape through saltational evolution (like omicron) can lead to decreased neutralization by already available antibodies, resulting in increased immune evasion.
This mutation is especially concerning, as it is capable of evading antibodies generated by previous infection or vaccination. As a result, it has the potential to cause reinfections in individuals who have already been infected or vaccinated.
Furthermore, the unpredictable number of mutations that can occur in the offspring of Pirola is a significant concern. This unpredictability can lead to the emergence of new variants that may cause more serious public health implications. It is essential to monitor the situation closely and take appropriate measures to prevent the spread of these new variants.
