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Coronavirus: an evolutionary perspective and why Biology is the solution (Part I)

We hear a lot about the clinical and epidemiological aspects of the coronavirus outbreak these days. We decided to look at it from the biological and evolutionary perspective – likely the only perspective that will provide answers and solutions to this global threat.


Is coronavirus a new thing?

No. Coronaviruses are a group of viruses that cause different diseases in mammals and birds. Whereas they tend to cause upper respiratory infections in humans and chickens, they rather cause diarrhea in cows and pigs.


Human coronaviruses were first characterized in the 1960s (1,2) and are known to be responsible for a substantial proportion of upper respiratory tract infections. We know 7 types of human coronaviruses to date, namely HKU1, NL63, OC43 and 229E, which are usually associated with mild symptoms; and SARS-CoV, MERS-CoV and SARS-CoV-2can cause severe disease (3). Many more coronaviruses are known to infect different animals.


Coronaviruses were initially put under the spotlight with the SARS-CoV epidemic between 2002 and 2003, which started in China and yielded over 8,000 cases and under 1,000 deaths (4). In 2012, MERS-CoV appeared in Saudi Arabia, with about 2,500 cases and almost 1,000 deaths reported since then (this outbreak is actually still ongoing) (5).


Between these two outbreaks, in 2007, a group of experts warned that coronaviruses are well known to undergo genetic recombination, which may lead to new genotypes and outbreaks. The presence of a large reservoir of SARS-CoV-like viruses in horseshoe bats, together with the culture of eating exotic mammals in southern China, is a time bomb. (6).


How did SARS-CoV2 appear?

There have been speculations about the origin of the virus responsible for the current coronavirus outbreak. Conspiracy theories speak about its purposeful release as a bioweapon or an accidental escape from a laboratory. This latter option has been reported in the past (7) but a recent article which analyzed at the genome of SARS-CoV2 reached to the conclusion that this virus is clearly not a laboratory construct or a purposefully manipulated virus. The authors of this article advocated for a generation by natural selection from a natural, existing coronavirus, either before or after it jumped from animals to humans (3). Both this publication and a different one (8), still under review, seem to point in the direction that SARS-CoV2 may have originated from the recombination of two different viruses which infected non-human mammals: the virus RaTG13 from bats and a coronavirus isolated from the Malaysian pangolin. According to these studies, these viruses may have merged their genetic material (RNA) to make a new virus, with the bat virus providing the largest part of the genetic material, and the pangolin virus supplying a component key to the infectivity and pathogenicity of SARS-CoV2: the gene coding for the virus’ S protein, responsible for the binding to its receptor in the human body, the ACE (Angiotensin Converting Enzyme 2). They know this because the genome of SARS-CoV2 looks very similar to that of the bat virus, however the S protein of SARS-CoV2 looks almost identical to the one of the pangolin virus.


In previous coronavirus outbreaks, MERS was shown to be originally present in bats, with camels as a possible reservoir, whereas the origin of SARS-CoV1 is unclear.


Is then SARS-CoV2 a mutation?

It seems like it, and if the theory mentioned above is true, definitely yes. Whereas the most famous cause of mutation is what are technically known as substitutions (i.e. a letter in the genome is replaced by a wrong one), genomic recombinationor reassortment is also a common source of mutation. It happens, in fact, every time humans generate new eggs or sperm cells as an evolutionary means to increase the genetic richness in the population. As a larger-scale mutation, recombination potentially generates living organisms with more significant changes substitution.


Substitution and other means of mutation can also be responsible for the generation of SARS-CoV2. The genome of this virus is made of a single strain of RNA, like the genome of many others, instead of DNA. This is initially not extraordinary. However, RNA is intrinsically more prone to experience mutations than DNA, up to 10,000 times more likely (9). This means that this coronavirus may be changing fast, which has been suggested as one of the reasons why its death toll seems to be different between China and Europe (10). However, this seems not to be the case (11), although there is probably not yet enough information to know for sure. Both substitution and recombination are non-mutually exclusive and may have played and be playing a role in the origin and virulence of SARS-CoV2.


In fact, the swine influenza virus H1N1 from the 2009 outbreak is thought to have emerged via this reassortment mechanism (12-13).


Why (always) bats?

Bats are blamed for the most mediatic severe diseases outbreaks. The ebola outbreak between 2011 and 2016 is thought to have originated in them (14), as well as other terrifying diseases such as Marburg, Nipah and Hendra viruses. And now coronavirus.


Bats are good vectors for viral diseases for three different reasons: first, because they live in communities in which they are in close contact with one another (i.e. no social distancing), making spread easier; second, they can fly, so they can spread their viruses in different geographies; and third, and most importantly, since flight is an energy-demanding physical exercise, their body temperatures are very high when they fly. In fact, they can reach temperatures of up to 42ºC. These high temperatures are capable of maintaining their viruses at bay, which makes them asymptomatic for the diseases they carry around. However, this also means that the viruses that can survive in bats, even if somehow attenuated when in bats, can perfectly live and infect humans at 37ºC and withstand normal human fever of 38-39ºC.


Fever is in fact one of the main mechanisms our body uses to kill pathogens. However, in many viruses originated in bats, our fever is too mild to kill them and therefore or body is caught by surprise and struggles to kill the pathogen by that means.


How do experts expect SARS-CoV2 to evolve?

From the biological perspective, viruses are parasites to humans. Indeed, they are obligate parasites since they need our cells to replicate. Even though viruses do not think or know, their genetic makeup is an almost perfect machine for continuous replication, and hence replication as much and as fast as possible may be considered their goal. Once they infect a person, they start to replicate at the expense of the energy of the cells of their host, which may die in this process – hence leading to symptoms and ultimately death of the human host in some cases. However, in most cases, after some days of infection the human immune system is capable of controlling the situation and kill the virus. It is therefore crucially important for the virus to spread and jump to a different host to restart the cycle and perpetuate its lineage. The longer they can stay in a single host, the more likely they will be to spread to other hosts, and so on, and the best way to stay in a host for longer is not killing the host too fast, hence not causing an extremely potent immune reaction.


SARS-CoV2 is a novel type of virus which just made its host jump recently, and may therefore not be completely adapted to its new host – humans – thus aiming at replicating too fast, so fast that they cause a deadly disease in a short period of time. Despite their well proven capacity to spread with this strategy, it is to be expected that less aggressive variants of the virus will be able to spread to more hosts and therefore may end up dominating the viral population. In other words, as in many other viral diseases (15), it is expected that this coronavirus adapts to its new host and becomes milder. This phenomenon is the one many viruses have evolutionarily followed, causing long-lasting or even lifelong infections, and is observed at its extreme in the viruses that have adapted so well to ourselves that ended up actually buried in our genome. It is believed that between 5-10% of the human genome is made of viruses (16) and that they played a huge role in our evolution.


Even though pathogenicity attenuation is a likely scenario in the long run, it is equally likely that coronavirus will spend some (evolutionary) time exploring the limits of its host. And the problem is that its new host is us.


References

(1) https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(66)92364-6/fulltext

(2) https://journals.sagepub.com/doi/abs/10.3181/00379727-121-30734)

(3) https://www.nature.com/articles/s41591-020-0820-9?error=cookies_not_supported&code=0f99aba3-6da1-4e1e-90f4-0bb4a32c86fa&fbclid=IwAR3072rYJCbeSiO1FIyY-_PPKXkppmT2RTFi6wP39VdaA7DBEpqqUekbiIY, https://www.sciencedirect.com/science/article/pii/S0065352718300010?via%3Dihub

(4) https://www.who.int/ith/diseases/sars/en/

(5) http://applications.emro.who.int/docs/EMRPUB-CSR-241-2019-EN.pdf?ua=1&ua=1

(6) https://cmr.asm.org/content/20/4/660

(7) https://www.nejm.org/doi/full/10.1056/NEJMoa032565

(8) https://www.biorxiv.org/content/10.1101/2020.02.17.951335v1

(9) https://jvi.asm.org/content/84/19/9733)

(10)https://www.express.co.uk/news/world/1257128/coronavirus-new-strain-spain-italy-china-latest-covid-19-europe-wuhan

(11)https://www.nature.com/articles/d41586-020-00154-w

(12)https://www.sciencedirect.com/science/article/pii/S0042682208004571

(13)https://www.nature.com/articles/nature08182

(14)https://www.sciencemag.org/news/2019/01/bat-species-may-be-source-ebola-epidemic-killed-more-11000-people-west-africa

(15)https://www.nature.com/articles/s41579-018-0120-2

(16)https://mobilednajournal.biomedcentral.com/articles/10.1186/s13100-018-0142-3

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