Scientists at the University of Ottawa in Canada concluded that the transition of SARS-CoV-2 from bats to humans has occurred due to stray dogs which could become intermediate hosts of the coronavirus. The article calls one of the main causes of the pandemic, published in the journal Molecular Biology and Evolution.
The researchers studied 1252 full-size genome of coronaviruses, including the ancestor of SARS-CoV-2 and its closest relative, the bat coronavirus BatCoV RaTG13 with a 96-percent match of the entire set of DNA.
In humans and mammals, there is a ZAP antiviral protein, which prevents the multiplication of the infectious agent in the cell and destroys its genome. Inside the RNA genome of the coronavirus has the dinucleotide — CpG sites, consisting of a cytosine followed by a guanine. CpG are targets for the immune system, which destroys the infection. ZAP present inside of human lungs and in large quantities are produced in the bone marrow and lymph nodes. However, ZAP is ineffective if the virus few CpG sites.
It turned out that the ancestor of SARS-CoV-2, and BatCoV RaTG13 there is the least number of CpG sites among all other related coronaviruses. While BatCoV RaTG13 was allocated in 2013 but not sequenced. Otherwise, knowledge of the nucleotide sequence of this virus would be a warning about a potential threat to people, as low CpG means high resistance of the pathogen to the immune system.
Canine coronaviruses that infect tissues of the digestive system, have the same level CpG, like SARS-CoV-2 and BatCoV RaTG13. In addition, for penetration into the cell coronavirus cellular receptor ACE2, found in abundance in the tissues of the small intestine and the duodenum. This is consistent with the theory that the ancestor of SARS-CoV-2 initially infect the intestines of stray dogs, which led to the rapid evolution of infectious agents and their penetration into the human body. A high proportion of people with COVID-19 also suffer from bowel disorders.
According to the final script, the coronavirus passed from bats, stray dogs who eat bat meat. Then, presumably strong selection against CpG in the genome of viral RNA promoted the rapid evolution of the virus in the intestine and led to a decrease in the level of CpG. This allowed the virus to escape from ZAP-mediated immune response to human and become a serious human pathogen.
