BtCoV/4991
"At the junction of the S1 and S2 protein subunits, COVID-19 has just such a polybasic cleavage site that uses the host cell enzyme furin, which is found in many human organ systems and known to be involved in the pathogenic processes of viruses, for example, HIV, Ebola and various strains of coronavirus.

The presence of the furin polybasic cleavage site may explain clinical reports of COVID-19’s ability to infect a variety of organ systems.

The furin polybasic cleavage site in COVID-19 can be roughly defined by the amino acid sequence SPRRARS, which is Serine-Proline-Arginine-Arginine-Alanine-Arginine-Serine, where the cleavage takes place at the R-S junction.

Within that broader sequence, the minimum sequence for a furin cleavage site is R-X-X-R, where Arginine (R) occurs in the 3rd and 6th positions and positions 4 and 5 can be any amino acid, but activity of the furin cleavage site can be significantly enhanced with a basic amino acid like Arginine in the 4th position, as occurs in COVID-19.

It is very important to note that the furin polybasic cleavage site in COVID-19 is unique and has not been found in any of the coronaviruses yet identified as close relatives.

Remarkably, however, such sequences do exist in other viruses, including coronaviruses not directly related to COVID-19. [..]

It is also interesting to note that the S2′ sequence of bat coronavirus CoVZX21, often cited as a close relative of CoVid-19, has an identical amino acid sequence of SKPSKRS at that position, but is demonstrably different at the critical S1 cleavage site.

The bioengineering capability to insert polybasic cleavage sites into the coronavirus S1 protein is well-established, already from 2006.

Scientists in China have used site-directed mutagenesis to alter the cleavage site of an infectious bronchitis virus by introducing basic amino acids, thereby increasing its pathogenicity and resulting in a “gain of function” such that the new virus was capable of infecting the brain producing “severe encephalitis.”

Applying the bioengineering techniques of recombination, site-directed mutagenesis and reassortment, CoVid-19 could have been created through the introduction of a furin polybasic cleavage site onto an appropriate coronavirus “backbone” from the catalogue of isolated strains in Chinese laboratories.

All of the above could be considered coincidental except for the fact that no clear evolutionary pathway has been identified that would explain the presence of COVID-19’s furin polybasic cleavage site, especially given its enhanced pathogenic significance.

It is also strange that with all the information publicly available, the most widely cited article by many scientists and media, “The proximal origin of SARS-CoV-2,” never mentions BtCoV/4991.

And how did a coronavirus, whether it be RaTG13 or BtCoV/4991, isolated from bats in Yunnan Province, nearly 1,000 miles away, end up in the Wuhan Seafood Market, if that was indeed the source of the outbreak?

Or, more likely, was it the result of a leak from a Wuhan laboratory, where experiments were being conducted on a variety of bat coronaviruses?"

Lawrence Sellin, Retired US Army Colonel

https://www.wionews.com/author/lawerence-sellin