Tracking The Origin Of Coronaviruses Via Viral Genome Sequence Analysis
05/21/2025
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“You are welcome to my opinion.”
-William F. Buckley
Background. In early 2020, during the first weeks of the COVID pandemic, an unsubstantiated rumor circulated (and is still around) that the CoV-2 virus that caused the pandemic was a biological weapon created by the Chinese Army. However, a group of scientists analyzed the genome sequence of the spanking new CoV-2 virus and rejected that idea saying there was no molecular evidence that the virus was man-made. Although they couldn’t rule out an accidental lab leak, they favored a natural origin of the CoV-2 virus at the time. Fast forward several years and the science still predominately favors the notion that the virus arose from a wild animal found at the Wuhan live market.
Eight of 18 US intelligence agencies have also examined the origin of the CoV-2 virus with mixed conclusions. Despite what scientists believe, the FBI, and more recently the CIA have come out in favor of an escape from the Wuhan Institute of Virology, although that conclusion is made with only the lowest of confidence. The Department of Energy intelligence folks also concluded with low confidence that the virus escaped from a different lab in Wuhan. Note that the intel community’s definition of low confidence intelligence is “that the information’s credibility and/or plausibility is uncertain, that the information is too fragmented or poorly corroborated to make solid analytical inferences, or that reliability of the sources is questionable.” Meanwhile, the remaining five intelligence agencies do not favor a lab origin scenario.
Importantly, the three agencies that favor a lab origin for the virus have not made their evidence public, so scientists cannot evaluate the bases for their conclusions. In contrast, several peer-reviewed science papers have been published on the topic and all conclude that the virus came from wild animals. Their prevailing understanding is that the virus then entered humans at the Huanan Seafood Market in Wuhan.
One of the most common arguments for the lab origin of CoV-2 is that the virus first infected humans in a city that was hundreds of miles away from where bat coronaviruses are endemic. Proponents of lab-leak theories have pointed to the long distance between Wuhan and the locations where the closest relatives of CoV-2 have been found as evidence for a lab leak. They believe that Wuhan is too far from where coronavirus-infected bats roamed for bats to be the source of human-infecting CoV-2. Furthermore, Wuhan has a coronavirus research lab (the Wuhan Institute of Virology or WIV). If Wuhan was too far for bats to fly and then infect wild mammals, some people assumed that scientists at the WIV must have developed the virus in a lab from which it either escaped or was released.
However, it is very relevant to note that in 2002 the first coronavirus, CoV-1, began infecting humans in Guangdong Province, China, which also was hundreds of miles from where bat coronaviruses are found. Notably, no lab in Guangdong Province studied coronaviruses. It was determined that a CoV-1-related coronavirus circulating in horseshoe bats jumped into raccoon dogs and other wild mammals in southwestern China. Some of those animals were caught and transported by humans for sale in markets in Guangdong where the coronavirus jumped again, into humans. The result was the first SARS pandemic, which spread to 33 countries and claimed 774 lives before non-pharmacological measure (read social isolation and masks) convinced it to quickly peter out in 2004 before any vaccine or medicine to treat it was developed. A few months into the first pandemic, scientists discovered the CoV-1 coronavirus that caused human disease (SARS) in mammals known as palm civets, which were sold in a market at the center of the outbreak hundreds of miles from where the virus was endemic. That was the smoking gun. It was concluded that the virus arrived there not by bat migration, but was carried there in infected animals by traders who sold the animals in the market. Wildlife animal traders were responsible for the fast appearance of the CoV-1 virus so far away.
The Recent Study. Seventeen years after the first SARS pandemic began in 2002, another coronavirus, CoV-2, suddenly appeared and infected people in Wuhan, China launching the COVID pandemic that ravaged the world and is still with us. Like CoV-1, CoV-2, also first appeared several hundred miles from where coronavirus-infected bats are found. How did the virus get to Wuhan? Was it carried by bats whose average home range is about ½ mile and are not migratory (unlikely)? Was it created and released from the lab in Wuhan that did research on coronaviruses, or, like CoV-1, did it arrive with animals brought to the city by animal traders? New research published in the May 2025 edition of the journal Cell indicate that animal traders brought the CoV-2 virus with them along with the animals they sold in the live market.
In the study, an international team of researchers mapped the evolutionary and geographic history of coronaviruses by first sequencing the genomes of 248 coronaviruses from bats. They then compared the genetic similarities and difference between all the different viral genomes to the known genome sequences of CoV-1 and CoV-2. From these data, they were able to use evolutionary modeling techniques to reconstruct relationship trees and dissect the evolutionary history of the coronaviruses that cause both SARS and COVID. The researchers then showed that the spread of the CoV-2 virus doesn’t support natural dispersal by the native horseshoe bat host, or its creation in a lab. They instead found that CoV-2 dispersion mimicked that taken by CoV-1.
As coronaviruses infect animals, different types of the virus sometimes ended up inside the same cell. When the cell makes new viruses, it can accidentally create viral hybrids that carry genetic material from both of the different coronaviruses. This mixing of the genetic information is called recombination. Flu and other viruses are very capable at recombining and forming novel mosaic viruses. It turns out, coronaviruses are pretty adept at recombination too and they use the same genetic regions to repeatedly recombine over eons of time. Therefore, in order to examine the relatedness of the different bat coronaviruses, the researchers focused on regions of the genome that were not involved in such recombination in order to more closely follow the same evolutionary history of each genome and compare that to the non-recombinant regions (NRR) of CoV-1 and CoV-2. The sequences of all so-called “non-recombinant regions” or NRRs were compared and from the mutations identified in each region, a “molecular clock” was determined in order to date the emergence of each viral variant.
The data showed that ancestors of both human coronaviruses circulated in bats across much of Southeast Asia for thousands of years. The horseshoe bat species that hosts the coronaviruses has been around for over 13 million years. So the virus had a constant host in which to mix and mutate.
In 2001, just a year before the SARS pandemic started in Guangdong, the Cell paper reports that CoV-1 underwent its last genetic mixing in bats. And since Guangdong is several hundred miles from the ancestral region of CoV-1, infected bats would not have been able to bring the virus to the region in just a year. Instead, researchers generally agree that this CoV-1-similar virus from bats infected wild mammals that were later transported to Guangdong for sale in the city’s live animal markets. A few months after the start of the SARS pandemic, researchers discovered CoV-1 in palm civets and other wild mammals for sale in those markets.
The researchers also found a similar evolutionary and dispersal pattern when they examined CoV-2 and its related coronavirus sequences. The last recombination in bats took place between 2012 and 2014, just five to seven years before the COVID pandemic began in Wuhan several hundred miles to the Northeast. Researchers believe that, as with CoV-1, a predecessor to the CoV-2 virus entered and circulated in wildlife, which were then transported by traders to Wuhan for sale in its live markets. This explains how the virus could travel such long distances in a short time. This evolutionary pathway is wholly inconsistent with a lab origin for the CoV-2 virus.
The researchers argue that these new research findings agree with earlier studies that they published in 2022 and which were described in these pages. Those studies provided evidence that the Huanan Seafood Market, one of four live markets in Wuhan, was where the COVID pandemic began. Wild mammals were sold there and all the earliest cases of COVID were centered around that market and not around the other markets or around the lab, which is seven miles away from the market. Chinese researchers also collected related strains of CoV-2 carrying a few distinct mutations from the market stalls and wastewater. In fact, the researchers concluded that the pattern of these mutations showed that the virus had twice spilled over to humans from wild mammals at the market.
However, at the end of 2019 when it was first suspected that the market might be the source of a novel pneumonia, wildlife vendors at the Huanan market quickly removed their animals from the stalls before scientists could study them. And once China put a stop to wildlife sales, traders and farmers culled their animals so they could not be tested for the virus. That is part of the reason why the CoV-2 smoking gun (i.e., an animal infected with CoV-2) has been so hard to find.
Bottom line. While this recent evidence is consistent with an animal origin of the CoV-2 virus, it still is not definitive proof. But, this research adds to the growing circumstantial argument that the virus migrated from a bat into wildlife that was sold at the Wuhan market. A “smoking gun” remains to be found to prove with certainty an animal vs lab origin for the virus. Note that it took 30-some years to find the source of the HIV virus, and we still do not know where the Ebola virus came from. So, we keep looking for unequivocal evidence to prove the origin of CoV-2 while realizing we might never find a smoking gun and will have to rely on the preponderance of evidence, which so far favors the animal origin of CoV-2.