SARS-CoV-2 had a stronger bond to ACE2 on human cells than any of the other animal species tested, including bats and pangolins. It would be expected that if one of the animal species was the source of the virus, it would have the strongest viral binding.
Scientists studying SARS-CoV-2, the virus that caused the COVID-19 pandemic, determined that the virus is most suited to infect human cells rather than bat or pangolin cells, raising new doubts about its origin.
In an article published in the Nature journal Scientific Reports, Australian scientists revealed how they utilized high-performance computer modeling of the SARS-CoV-2 virus’ form at the start of the pandemic to forecast its capacity to infect people and a variety of domestic and exotic animals.
Their research aimed to identify any intermediate animal vectors that may have played a role in the transmission of the bat virus to humans, as well as to better understand the risk posed by the susceptibilities of companion animals like cats and dogs, as well as commercial animals like cows, sheep, pigs, and horses.
The researchers from Flinders University and La Trobe University carefully constructed computer models of the main ACE2 protein receptors for each species using genetic data from the 12 animal species. The strength of the SARS-CoV-2 spike protein’s binding to each species’ ACE2 receptor was then calculated using these models.
Surprisingly, SARS-CoV-2 bonded to ACE2 on human cells stronger than any of the other examined animal species, including bats and pangolins, according to the findings. If one of the animal species examined was the source of the virus, it would be anticipated to have the strongest viral binding.
“Humans showed the strongest spike binding, consistent with the high susceptibility to the virus, but very surprising if an animal was the initial source of the infection in humans,” says La Trobe University Professor David Winkler.
“The computer modeling found the virus’s ability to bind to the bat ACE2 protein was poor relative to its ability to bind human cells. This argues against the virus being transmitted directly from bats to humans. Hence, if the virus has a natural source, it could only have come to humans via an intermediary species which has yet to be found,” says Flinders affiliated Professor Nikolai Petrovsky.
The SARS-CoV-2 virus also bonded quite tightly to ACE2 from pangolins, a rare exotic ant-eater found in some regions of Southeast Asia and occasionally used as food or traditional medicine, according to the team’s computer modeling. Pangolins had the greatest spike binding energy of all the animals studied, substantially greater than bats, monkeys, and snakes, according to Professor Winkler.
“While it was incorrectly suggested early in the pandemic by some scientists that they had found SARS-CoV-2 in pangolins, this was due to a misunderstanding and this claim was rapidly retracted as the pangolin coronavirus they described had less than 90% genetic similarity to SARS-CoV-2 and hence could not be its ancestor,” Professor Petrovsky says.
The particular portion of the pangolin coronavirus spike protein that binds ACE2 was almost identical to that of the SARS-CoV-2 spike protein, according to the new study and previous research.
“This sharing of the almost identical spike protein almost certainly explains why SARS-CoV-2 binds so well to pangolin ACE2. Pangolin and SARS-CoV-2 spike proteins may have evolved similarities through a process of convergent evolution, genetic recombination between viruses, or through genetic engineering, with no current way to distinguish between these possibilities,” Professor Petrovsky says.
“Overall, putting aside the intriguing pangolin ACE2 results, our study showed that the COVID-19 virus was very well adapted to infect humans.”
“We also deduced that some domesticated animals like cats, dogs and cows are likely to be susceptible to SARS-CoV-2 infection too,” Professor Winkler adds.
There are presently two primary hypotheses for how the virus infected people, which is a very significant and unresolved topic. The virus may have been transmitted to humans from bats via an unidentified intermediary animal (zoonotic origin), however it cannot be ruled out if it was accidentally discharged from a virology lab. To establish which of these theories is accurate, a rigorous scientific, evidence-based investigation is needed.
The researchers conclude that understanding how and where the SARS-CoV-2 virus evolved to become such an efficient human pathogen remains a mystery, but that discovering the disease’s roots would aid attempts to safeguard mankind from future coronavirus pandemics.