Relative of Covid-causing Virus Found in Bats in Asia

Researchers from France and Laos have identified for the first time a bat virus that is closely related to the one that causes Covid-19 and can invade human cells using the same method as the pandemic virus.

This is an important step towards understanding the origins of the disease, in addition to reinforcing what many scientists have been warning for decades: pathogens with the potential to cause new infectious diseases in our species exist in abundance in nature.

The study, which has just appeared in one of the world’s leading scientific journals, Nature, was coordinated by Marc Eloit, from the Pathogen Discovery Laboratory at the Pasteur Institute in Paris. Scientists from the Pasteur Institute branch in Laos and other institutions in this Southeast Asian country, which borders nations such as China, Thailand and Vietnam, also sign the work.

“The work is very well done, and it’s a mixture of surprise and ‘I told you so’, actually”, says Flávio Guimarães da Fonseca, a researcher at UFMG and president of the Brazilian Society of Virology. “Since before the pandemic, we have been putting together pieces and realizing that the coronaviruses that use these routes of infection are much more widespread than we used to think.”

The 46 species of bats analyzed in the study by Eloit and his colleagues were collected in caves in Laos. It has long been known that the region’s flying mammals are among the possible reservoirs of “wild” relatives of Sars-CoV-2, the cause of Covid-19. Viruses identical to it have not yet been detected in nature, but pathogens whose genetic material is more than 95% similar to that of Sars-CoV-2 all come from Asian bats.

Even these “first cousins” of the pandemic coronavirus, however, have significant differences at one crucial point: the tip of the so-called spike protein, which the virus uses to attach to specific entry points on the surface of human cells. This is the receptor designated by the abbreviation ECA2. It is present in a wide variety of cells, in different tissues of the body, which explains the multiple effects of Covid-19, which go far beyond respiratory problems.

If a bat virus really made the jump from one species to another and started infecting humans, as most scientists believe, it needed to have the right “key” in the spike protein to open the lock on the ACE2 receptor, since its shape changes from cells from one species to another. No bat viruses with the correct key had been found to date.

In the new research, the international team obtained samples of blood, saliva, urine and feces from 645 bats, using a method that “hooks” the genetic material of several types of coronavirus. Then, they decoded the genome of all the coronaviruses they found and compared it to online catalogs of these viruses. Several pathogens identified by this method showed great genetic proximity to Sars-CoV-2, especially the one designated by the acronym BANAL-52, which has 96.8% similarity to the one that causes Covid-19.

And the analysis of the spike protein tip, precisely the most important part for the interaction with the receptor of the invaded cells, revealed even greater similarities. This similarity is evaluated by the number of amino acids, the components that together make up proteins. Of the 17 amino acids that interact with the ACE2 receptor in the virus that affects humans, three Laotian bat viruses, including BANAL-52, carry 16 or 15 that are identical – as if they had a key with one or two small slots. less, shall we say, but still apparently functional.

This is what further tests involving the spicules and the viruses themselves demonstrated. In the test tube, the versions of the spikes present in them were shown to be able to interact with human ACE2 and also to promote the invasion and multiplication of the virus inside human cells. The effectiveness of the process was similar to that of the original Covid-19 virus (prior to the variants that began to emerge after its spread around the world).

The team also carried out an evolutionary analysis of the genetic material of the bat viruses collected so far and of Sars-CoV-2. The conclusion is that, for now, BANAL-52 and two other similar viruses are the closest relatives of the one causing Covid-19, while a few more viruses isolated in China appear to have contributed to the pathogen that affects humans through recombinations of their genomes, that is, exchanging genetic material with each other.

This mixture is not very surprising, because Southeast Asia’s large limestone caves are home to populations of several bat species that cluster together, greatly facilitating the exchange of pathogens between the animals. Deforestation and increasing animal trafficking, in turn, increase the chances of their contact with humans.

“The work reinforces the idea of ​​the origin of Sars-CoV-2 in a species of bat and shows that coronaviruses like these will, from time to time, emerge”, says Maurício Lacerda Nogueira, virologist at the Faculty of Medicine of São José do Rio Preto (São Paulo countryside). “It also shows the importance of surveillance in relation to these reservoirs of new viruses.”

“We have to be very attentive to what is happening. It is typical of the ecological situation that human beings have reached: today, we are a much more intrusive, much more invasive species, and consequently these phenomena are becoming more frequent because of the greater contact with wild species that harbor these viruses”, says Flávio da Fonseca.