SARS-CoV-2-PLpro cuts human proteins ubiquitin and ISG15, which help maintain protein integrity. "The enzyme acts like a molecular scissor," Dr. Olsen said. "It cleaves ubiquitin and ISG15 away from other proteins, which reverses their normal effects."

In addition to removing the protection of DNA repair, autophagy, protein translation and exosome secretion, cleaving ubiquitin and ISG15 allows the "cell gates" to be opened. This gives pathogens, deleterious aggregates and prions the ability to spread.

It has been observed that SARS-CoV-2 causes contradictory actions for its survival.

On the one hand, the ubiquitination of p53 is good for SARS-CoV because the ubiquitinated p53 cannot inhibit SARS-CoV replication. On the other hand, the ubiquitination of NF-κB inhibitor (IκBα), TNF receptor-associated factors (TRAFs), and stimulator of interferon gene (STING), and the ISGylation of targeted proteins are bad for SARS-CoV because these ubiquitination and ISGylation initiate the innate immune response and antiviral state.

This is, perhaps, intentional design, as the purpose of the virus is to induce prion disease, not necessarily to cause a severe respiratory disease. 

One of the S Protein functions after post-translational modification is that of protein folding and trimerization. 

SDisulfide bridgeProtein folding and trimerization (MHV)

N-glycosylationConstitute neutralizing epitopes (TGEV, BCoV, SARS-CoV, IBV); mutations lead to antigenic shift (IBV); membrane fusion (IBV); NOT required for receptor binding (SARS-CoV); lectin-mediated virion attachment (SARS-CoV); activation of innate immunity (TGEV) Palmitoylation S protein trafficking and folding.

This is the mechanism by which Cholingeric Neuron Degenerative Disease begins, and perhaps other SARS-CoV-2 induced prion diseases.

(MHV, SARS-CoV); viron assembly and infectivity (MHV, TGEV); interaction between S and M (MHV)

The spike protein induces misfolding, while simultaneously disabling the protection of the Ubiquitin-Proteasome System.