It Takes Two: COVID-19 Coronavirus Possibly 'Chimera' of Two Distinct Viruses

In the age of the novel coronavirus, weeks seem like years — especially when there's so much to learn about COVID-19, and the virus behind it: SARS-CoV-2. But where there is danger, rumors abound.

Between the science and the gray gaps of unknowns rests the question of origin: from where in the world did the COVID-19 coronavirus come? A new study suggests it's a chimera between two pre-existing viruses.

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COVID-10 coronavirus of unknown origins

Of all the animals carrying the disease, in which did COVID-19 happen? Was it a pangolin, a bat, or some other wild species? It could have been a forest or a cave; in the Chinese province of Hubei, or possibly elsewhere.

In December of 2019, 27 of the first 41 people hospitalized (roughly 66%) moved through a market in the heart of the city of Wuhan, in China's Hubei province. However, a study carried out at Wuhan Hospital shows the first human case identified didn't frequent that market.

On the contrary, a molecular dating estimate based on SARS-CoV-2 genomic sequences suggests a November origin. This raises serious questions about the link between wildlife and the COVID-19 epidemic.

Genome data

Chinese researchers rapidly sequenced SARS-CoV-2 genome data. The RNA molecule consists of roughly 30,000 bases containing 15 genes, including the dreaded S gene that codes for a protein located on the surface of the viral envelope. To contrast, compare with the human genome, which takes the form of a double helix of DNA roughly 3 billion bases in size and containing roughly 30,000 genes.

Comparative analyses of the genomes show that the SARS-CoV-2 genome belongs to the Betacoronavirus group, very close to the SARS-CoV responsible for the epidemic of acute pneumonia that came to the fore in the Chinese province of Guangdong in November 2002, sweeping through 29 countries in 2003.

In total, 8,098 cases of SARS-CoV, with 774 deaths. We know that bats of the genus Rhinolophus (which might live in caves) were the reservoir of this virus and that a little carnivore called the palm civet (Paguma larvata) might have functioned as an intermediate host between bats and the early human cases of SARS.

Since that time, most Betacoronaviruses were discovered in bats, but also in humans. For example, another strain known as RaTG13 was isolated from a bat of the Rhinolophus affinis species from China's Yunnan Province, described as notably similar to SARS-CoV-2, with a 96% similarity in genome sequence; nearly identical.

This means bats (specifically the species of the Rhinolophus genus) are the "reservoir" of the SARS-CoV and SARS-CoV-2 viruses.

Reservoir of ambiguity

The problem is in what we mean by "reservoir." In epidemiology, a reservoir is one or several animal species with little to no sensitivity to the virus, which means they serve as natural (or neutral) hosts to one or several viruses.

This absence of symptoms is explained by the effectivity of the host's immune system, one that helps them fight against excessive viral proliferation.

Mechanism for recombination

A recent study (under review) shows a genome of the coronavirus isolated from the Malaysian pangolin — called Manis javanica — is even less similar to SARS-CoV-2, with only 90% genomic overlap. This would mean the virus isolated in pangolins isn't responsible for the COVID-19 pandemic currently ravaging the world.

However, the coronavirus isolated from pangolin shows an incredible 99% similarity specific to the region of the S protein, corresponding to 74 amino acids related to the ACE (Angiotensin Converting Enzyme 2) receptor binding domain; the one with which the virus enters human cells to infect them.

Contrasting with this, the RaTG13 virus isolated from the R. affinis bat diverges significantly from that specific region (roughly 77% similarity, markedly lower). This means the coronavirus isolated from the pangolin can enter human cells, but the one from the R. affinis bat cannot.

Additionally, this extensive comparison analysis suggests the SARS-CoV-2 virus is the creation of recombination between two separate and distinct viruses — one close to RaTG13, and the other closer to the virus isolated in the pangolin.

Put simply, the COVID-19 coronavirus is a chimera between two other pre-existing viruses. For this to have happened, two distinct viruses need to infect the same organism simultaneously. While we don't know which animal (a pangolin, a bat, or some other species) played host to the chimeric mix, nor under what conditions the recombination took place, we're moving gradually closer to the solving the mystery of where and how the novel coronavirus came to be.