1.1  Background
As far as is known to history, no coronavirus [1] has been as disturbing to humanity as the human pandemic of the 2019 novel coronavirus [2] now known as SARS-CoV-2. In quick response to determination of the final version of the RNA sequence of the Wuhan seafood market isolate, the present author examined functional sites of SARS-CoV-2 that are highly conserved across the coronaviruses [3,4], and which thus likely to exhibit escape mutation that can quickly undo the good work of the developers of vaccines and therapeutic agents. So far, the published papers have concerned the spike glycoprotein [[3], [4], [5]]. Exploration of known and newly found proteolytic cleavage sites in the spike glycoprotein of SARS-CoV-2 that are well conserved is a popular area of inquiry for SARS researchers because such sites can interact with human host airway proteases that could be the target for protease inhibitors as potential drugs (e.g. Ref. [6]). The difficulty is that inhibiting the action of human proteins could have undesirable effects on the host [6], so parallel work on other kinds of functional sites in the coronavirus proteins is of great importance.
The present paper explores another potential functional site in the spike protein, but this one is a different because the site is not a proteolytic cleavage site, and it is not well conserved, except, it is argued, for a characteristic composition of particular amino acid residues. Expressed another way, there can exist certain subsequences of a protein sequence that are well conserved, but only in respect to some pattern or property that is less obvious than the order of amino acids. Finding them (or as is more correctly stated, predicting them) may therefore require a more subtle and, in the present case, novel bioinformatics tool, compared with the standard bioinformatics tools which were essential in the preceding papers [[3], [4], [5]]. Comparisons with other proteins as described below suggest that the subsequence of interest in this paper could have a crucial function, and a high degree of conservation is, even by itself, also a clue as having a role important to the virus [5]. Hence such a site may represent a potential therapeutic target, perhaps as well as representing a synthetic vaccine target. However, until very recently, that crucial function did not even seem to be possessed by SARS-CoV and SARS-CoV-2, and the details have yet to be elucidated.