A new study, involving the University of Cambridge and led by the Pirbright Institute, has identified key genetic changes in SARS-CoV-2—the virus that causes COVID-19—that may be responsible for the jump from bats to humans, and established which animals have cellular receptors that allow the virus to enter their cells most effectively.

The genetic adaptions identified were similar to those made by SARS-CoV—which caused the 2002-2003 SARS epidemic—when it adapted from bats to infect humans. This suggests that there may be a common mechanism by which this family of viruses mutates in order to jump from animals to humans. This understanding can be used in future research to identify viruses circulating in animals that could adapt to infect humans (known as zoonoses) and which potentially pose a pandemic threat.

"This study used a non-infectious, safe platform to probe how spike protein changes affect virus entry into the cells of different wild, livestock and companion animals, something we will need to continue monitoring closely as additional SARS-CoV-2 variants arise in the coming months," said Dr. Stephen Graham in the University of Cambridge's Department of Pathology, who was involved in the study.

In the 2002-2003 SARS epidemic, scientists were able to identify closely related isolates in both bats and civets—in which the virus is thought to have adapted to infect humans. However, in the current COVID-19 outbreak scientists do not yet know the identity of the intermediate host or have similar samples to analyze. But they do have the sequence of a related bat coronavirus called RaTG13 which shares 96 percent similarity to the SARS-CoV-2 genome. The new study compared the spike proteins of both viruses and identified several important differences.

SARS-CoV-2 and other coronaviruses use their spike proteins to gain entry to cells by binding to their surface receptors, for example ACE2. Like a lock and key, the spike protein must be the right shape to fit the cell's receptors, but each animal's receptors have a slightly different shape, which means the spike protein binds to some better than others.

To examine whether these differences between SARS-CoV-2 and RaTG13 were involved in the adaptation of SARS-CoV-2 to humans, scientists swapped these regions and examined how well these resulting spike proteins bound human ACE2 receptors—using a method that does not involve using live virus.

Issue is that RaTG13 appeared in Chinese lab database after it became clear that they need some bridge looking thingy for SARS-CoV-2.

Two other issues are that RaTG13 virus had been collected around 3 thousand km from Wuhan and no registered jumps to human of any similar viruses had been registered. In other words, number and complexity of mutations in few humans must be 1000x more than number of mutations that happened to coronavirus in around 200-300 millions people who got it (some estimate it as 700 millions already).

Another thing needing explanation is that most of differences and new parts comes from virus only collected in pangolins in a place tha is very far from bat virus collection. Also, except few directly involving Chinese researches no one have any proof of viruses collection at all. As all of them, 100% can be engineered.

https://phys.org/news/2021-01-genetic-enabled-sars-cov-humans.html

They demonstrated that bat and bird receptors made the weakest interactions with SARS-CoV-2. The lack of binding to bat receptors adds weight to the evidence that SARS-CoV-2 likely adapted its spike protein when it jumped from bats into people, possibly via an intermediate host.

Dog, cat, and cattle ACE2 receptors were identified as the strongest interactors with the SARS-CoV-2 spike protein. Efficient entry into cells could mean that infection may be more easily established in these animals, although receptor binding is only the first step in viral transmission between different animal species.

"As we saw with the outbreaks in Danish mink farms last year, it's essential to understand which animals can be infected by SARS-CoV-2 and how mutations in the viral spike protein change its ability to infect different species," said Graham.

Also it is lot of questions about spike protein that attach to ACE2 receptor and its efficiency. Researches showed that it is very close to theoretical maximum efficiency for such protein for ferrets, and it is exactly ferrets that are using in mass in bio labs for virus filtering and adaption.

It also explain why we see mass minks killings and so big fear as they are extremely close to ferrets.

New data showing that dog, cat, and cattle ACE2 receptors were identified as the strongest interactors with the SARS-CoV-2 spike protein also proves artificial origin, as good binding to this animals cells is require to cause maximum damage o human population.

Something clearly went bad as elites did not have enough time to test virus, we clearly openly saw same media promoting cat infection, but it proven to be false, on some stage cats immunity prevents virus spreading inside cells.