SARS-CoV-2 Virus –A Combination of Two Pre-Existing Viruses?

In the span of a few weeks, we have all learned about SARS-CoV-2 and the disease that it causes: COVID-19. However, there have also been a lot of misconceptions and myths surrounding it. And while the number of scientific articles on the SARS-CoV-2 virus is increasing, there are still many questions regarding its origins and evolution.

Where does it come from? From a forest or a cave in the Chinese province of Hubei – or was it engineered in a lab? In which animal species did it occur – a pangolin, a bat, or another wild species?  

In December 2019, 27 of the first 41 people hospitalized passed through a market in the heart of Wuhan city in Hubei province. However, a study conducted at Wuhan Hospital reveals that the very first identified human case of COVID-19 did not frequent this market. Instead. A molecular dating assessment based on the SARS-CoV-2 genomic sequences indicates that it originated sometime in November. This raises inquiries about the link between this COVID-19 pandemic and wildlife.

SARS-CoV-2 Genomic Data

The SARS-CoV-2 genome was promptly sequenced by Chinese researchers. It is an RNA molecule of around 30,000 bases. Moreover, it contains 15 genes including the S gene that codes for a protein located on the surface of the viral envelope. Comparative genomic analyses reveals that SARS-CoV-2 belongs to the group of betacoronaviruses and that it is very close to SARS-CoV which was responsible for an epidemic of acute pneumonia which appeared in 2002 in the Chinese province of Guangdong and spread to 29 countries in 2003.

A total of 8,098 cases were confirmed, including 774 deaths. It is known that bats of the genus Rhinolophus were the reservoir of the SARS-CoV virus and that a small carnivore – the palm civet – may have served as an intermediate host between bats and the first human case.

Since then, several betacoronaviruses have been identified, mainly in bats but also in humans. For instance, RaTG13, which was isolated from a bat of the species Rhinolophus affinis gathered in China’s Yunan Province has recently been described as very similar to the SARS-CoV-2 virus – with genome sequences identical to 96%. These results reveal that bats (particularly those of the Rhinolophus genus) comprise the reservoir of the SARS-CoV and SARS-CoV-2 viruses.

But, what exactly is a reservoir? Essentially, a reservoir is any person, animal, or substance in which an infectious pathogen naturally lives and reproduces, or upon which the pathogen primarily relies for its survival. Typically, the reservoir harbors the infectious pathogen without injury to itself and serves as a source from which other organisms can be infected.

Recombination Mechanism

On February 2020, scientists learned that a virus even closer to SARS-CoV-2 had been identified in pangolins. With a reported 99% genetic concordance, this suggested a more likely reservoir than bats. However, a recent study reveals that the genome of the coronavirus isolated from the Malaysian pangolin is less similar to SARS-CoV-2, with only 90% genomic concordance. This indicates that the virus isolated in the pangolin is not responsible for the COVID-19 pandemic.

However, the coronavirus isolated from the Malaysian pangolin is 99% similar in a specific region of the S protein, which matches 74 amino acids involved in the ACE receptor binding domain, the one that enables the virus to enter human cells to infect them. In contrast, the virus RaTG13 isolated from bat Rhinolophus affinis is very divergent in this specific region with only 77% similarity. This means that the coronavirus isolated from the Malaysian pangolin is capable of entering human cells, whereas the one from bat Rhinolophus affinis is not.

Moreover, these genomic comparisons suggest that the SARS-CoV-2 virus is the result of a recombination between two different viruses – one closer to the pangolin virus and one close to the RaTG13 virus. In other words, the SARS-CoV-2 virus may be a combination of two pre-existing viruses.

This recombination mechanism had already been defined in coronaviruses, particularly to explain the origin of SARS-CoV. It is vital to know that recombination results in a new virus that can potentially infect a new host species. For recombination to take place, the two divergent viruses must have simultaneously infected the same organism.

SARS-CoV-2 Virus: Natural Origins

Contrary to the rumors going around, the SARS-CoV-2 virus was NOT engineered in a lab.

Researchers at the Scripps Research Institute state that their genetic analysis of the SARS-CoV-2 virus and related viruses has found no evidence that the SARS-CoV-2 virus is the result of bioengineering in a lab. Rather, Kristian Andersen, an associate professor of immunology and microbiology at Scripps Research, states that “By comparing the available genome sequence data for known coronavirus strains, we can firmly determine that SARS-CoV-2 originated through natural processes.”

SARS-CoV-2 Virus Natural Evolution: The Evidence

To study the origin and evolution of the SARS-CoV-2 virus, scientists analyzed the genetic template for the viral proteins on the outside of SARS-CoV-2 that the virus uses to bind to cell surface receptors and gain entry into human cells. Scientists concentrated on two important features of the spike protein – the receptor-binding domain (RBD) and the spike protein’s polybasic furin cleavage site, which is involved in gaining entry through the human cell’s outer membrane.

Scientists found that the RBD portion of the SARS-CoV-2 spike proteins had evolved to successfully target a molecular feature on the outside of human cells known as ACE2. ACE2 is a receptor involved in blood pressure regulation. The SARS-CoV-2 spike protein was so effective at binding human cells that scientists concluded that it was the result of natural selection, not the product of genetic engineering.

The evidence for the natural evolution of the SARS-CoV-2 virus is further supported by data on the virus’ backbone – its overall molecular structure. If someone wanted to engineer a new coronavirus, they would have constructed it from the backbone of a virus known to cause illness and disease. However, the scientists discovered that the SARS-CoV-2 backbone was significantly different from those of already known coronaviruses and mostly resembled related viruses found in pangolins and bats.

These two features of the virus – the mutations in the RBD portion of the SARS-CoV-2 spike protein and its unique backbone – rules out genetic engineering as a potential origin for the SARS-CoV-2 virus.

Based on their genomic sequencing analysis, the scientists concluded that the SARS-CoV-2 evolution followed one of two possible scenarios:

  • The SARS-CoV-2 virus evolved into its current pathogenic state through natural selection in a non-human host, then jumped to humans. This is how previous coronavirus outbreaks started – with human contracting the virus after direct exposure to camels (in the case of MERS) and to civets (in the case of SARS).
  • A non-pathogenic version of the SARS-CoV-2 virus jumped from an animal host into humans, and then evolved to its current pathogenic state within the human population. For instance, a coronavirus from a pangolin could have possibly been transmitted to a human – either directly or through an intermediary host.

The Bottom Line

There are still many unanswered questions regarding the SARS-CoV-2 virus and the disease it causes, COVID-19. However, researchers and scientists are working tirelessly to find its cause and to ultimately develop a cure for this pandemic that is raging all throughout the world.

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