Relevant excerpts:

>So what’s the best hypothesis? The available data suggests a two-step process that may have given rise to SARS-CoV-2:

A bat coronavirus likely infected an intermediary animal (potentially a Malayan pangolin) where it recombined with a non-bat coronavirus.

Over time, either in the intermediary animal or while in humans, SARS-CoV-2 developed additional mutations: a polybasic cleavage site and a nearby o-linked glycan addition site.

It’s worth noting there are actually two competing hypotheses. In hypothesis 1, SARS-CoV-2 gains its new tools before spillover into humans. In hypothesis 2, SARS-CoV-2 gains these tools while amplifying in humans.

If hypothesis 2 is correct, then when SARS-CoV-2 first infected humans, it probably replicated and spread less well (like MERS, another human coronavirus). Over multiple replication cycles, the virus made mistakes and some mutants gained the advantage and began spreading efficiently among humans. If this is true, then we can implement better measures to monitor humans for new infections, and catch spillover viruses before they “get good” at spreading in humans.

Most scientists will look at the data gathered so far and say we’re on the right track because:

All the current data fits our hypotheses

Our hypotheses are the most parsimonious and best satisfy Occam’s Razor

Our hypotheses are testable and falsifiable

This strongly implies the virus was not designed or modified in a lab

A follow up section digs into two methods of man-made virus engineering. The article addresses each individually and concludes neither in isolation fits the bill. It does not address both in combination. Which is a glaring omission given that both methodologies being well defined mean that they can be applied in a staged manner trivially, and in fact, doing so would be, to me, the most practicable way to innovate. Apply every tool I know in discrete steps to leverage the best aspects of both methods.

Then there is this section:

>Second, what about the polybasic cleavage site and the o-linked glycan? We have seen, with other viruses, the ability to develop polybasic cleavage sites when put under just the right conditions for long periods of time. While unlikely, this piece of the virus could plausibly be developed through selection in a lab setting. However, what is near impossible is the development of the o-linked glycan addition motif. This is because the pressure to develop this glycan shield requires avoiding an intact immune system. This type of selection cannot occur using cell culture, and there is no known animal model that would allow for selection of human-like ACE2 binding and avoidance of immune recognition. This strongly implies SARS-CoV-2 could not have been developed in a lab, even by a system of simulated natural selection.

Which did not touch on whether O-linked glycan formation is a trait exclusive to human immune systems and not present in bats or pangolins, which are both jawed mammals in possesion of adaptive immune systems, capable of applying said pressure as far as I am aware.

This may be blatantly obvious to a zoologist, or immunologist, but the answer to such a question is not at all obvious to me. If there is someone with said knowledge or who knows someone with it, it would be much obliged for a sharing thereof.

Especially given that the chemical reaction is not exactly uncommon apparently.

https://en.m.wikipedia.org/wiki/O-linked_glycosylation