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The genetic study of the SARS-CoV-2 coronavirus and some of its closest relatives, such as those found in the bat or pangolin, has provided new clues about the origin of the outbreak in humans.
The analysis of the pathogen's RNA, which could also help to develop vaccines, indicates that an ancestor of the current virus evolved in the intestine of a mammal that lived in isolation or that few specimens remain, since it had little contact with our species . So he was able to mutate there for years. When the jump finally occurred, he was "human ready."
According to the research, published in Molecular Biology and Evolution , it is unlikely that the virus would infect people directly from the bat or pangolin. According to Xuhua Xia, professor of biology at the University of Otawa and lead author of the study, there is most likely an "animal X" that served as an intermediary.
The fight between the animals' immune system and the virus itself leaves its mark on the latter's genome, since the pathogen adapts to the environment it has invaded. SARS-CoV-2 has its own war scar, which is also what makes it so "stealthy and dangerous." There is very little CpG nucleotide in your RNA, allowing you to escape an antiviral protein called ZAP.
Since this property is "very rare among coronaviruses," our immune system "is not ready," Xia explains.
The question is: where and how did the lethal change occur? After studying various classes of viruses and their development in different tissues and species, the scientists found that evolution most likely occurred in the intestine of a species with an abundance of ZAP proteins. There he mutated and learned to survive the defenses of the hosts, who could have been, " for example, canids or humans that ingested bats ."
Wild dogs are candidates because other viruses have already been seen to adapt to their intestines, reducing the amount of CpG and becoming invulnerable to ZAP. Hence "the importance of monitoring viruses" in these animals, the study indicates. Although, as Xia qualifies, the conclusion is "speculative", since there may be more mammals with similar characteristics not identified. Furthermore, Xia remembers that there is no evidence that dogs are contagious or can be contagious .
Whatever "animal X" is, finding it could be key to developing new treatments. At the moment, the new study presents two tracks to develop possible vaccines. The first is that the virus manages to bypass the immune system thanks to its reduced amount of CpG in its genome. The second is that, despite this adaptation, it still retains some CpG, suggesting that it is "functionally important" for the pathogen. "Therefore, both increasing the amount of CpG present in SARS-CoV-2 and modifying the remaining Cpg could result in an attenuated virus that can be used as a vaccine ."
Direct transmission, unlikely
Analysis of the slight mutations in the different strains of the current coronavirus pandemic, from its inception in December 2019 to mid-March, has allowed researchers to calculate what its average variation is per day. With this data, they have estimated that both the viruses detected in the pangolin and those observed in bats are too distant relatives of the one that attacks people , so direct transmission from these animals seems unlikely.
In the case of the bat, the common ancestor from which both the coronavirus carried by this species and SARS-CoV-2 come would date from 1966, judging by the speed at which the strains change and the genetic differences that both pathogens exhibit. nowadays. For the pangolin, the similarity is even less, since it would lead us to a common ancestor in 1882 .
Furthermore, since all the strains studied in humans come from those identified in Wuhan, it is unlikely that the virus has been circulating between people for a long time, says Xia. It is not ruled out, however, that a parent of SARS-CoV-2 infected humans long ago without causing further harm, and then "passed on to other animals and acquired their current form."
In one way or another, 'animal X' is fundamental to understanding the disease. Especially since it does not seem that this species is affected too much. If it did, Xia argues, it would have been quickly identified and the risk of contagion would have been less. But we haven't found it yet, suggesting that its "viral mechanisms" are effective , and we might find "immune responses to virus infection" in them. That is, what everyone expects.
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