cause of COVID-19 amyloid accumulation may be known

[mellowtigger]

This is a combined Good News / Bad News situation, but this discovery is too important to skip this week, so I'm making a Moody Monday double post.

We already have reason to believe that all SARS-CoV-2 variants are neuroinvasive. We already know that "covid brain" is a real thing that happens. I previously worried that the S1 spike protein might be implicated, which would be bad news since the anti-vax crowd would misinterpret it. But it turns out to be more complicated and surprising.

Recently, we showed that viruses can induce aggregation of purified amyloidogenic proteins via the direct physicochemical mechanism of heterogenous nucleation (HEN). In the current study, we show that the incubation of HSV-1 and SARS-CoV-2 with human cerebrospinal fluid (CSF) leads to the amyloid aggregation of several proteins known to be involved in neurodegenerative diseases... Importantly, UV-inactivation of SARS-CoV-2 does not affect its ability to induce amyloid aggregation, as amyloid formation is dependent on viral surface catalysis via HEN and not its ability to replicate. Our results show that viruses can physically induce amyloid aggregation of proteins in human CSF, and thus providing a potential mechanism that may account for the association between persistent and latent/reactivating brain infections and neurodegenerative diseases.
- https://www.biorxiv.org/content/10.1101/2022.09.15.508120v1

This is only a PRE-print, so take it with some caution, but if confirmed then it is BIG news. It means the amyloidosis is NOT a result of malformed prion exposure as in mad cow disease. Instead, these malformed proteins develop spontaneously while in contact with SARS-CoV-2 in sufficiently saturated environment, like raindrops coalescing onto dust particles in the air. I downloaded the PDF, but I'm having a hard time figuring out exactly what virus surface is responsible. Do they mean a spike "S" protein or is it a membrane "M" (previously called envelope "E", apparently) protein?  It has implications for how safe the different vaccines are, since the point of any vaccine is to safely present the proteins of the disease virus itself.  Choose wisely, and don't select a protein that even alone can cause problems.

In a recent review, we outlined the physicochemical and thermodynamic basis of this interaction in light of the classical nucleation theory, where the presence of viral surfaces lowers the energy barrier for the phase transition of proteins from the soluble form into the solid amyloid form (21). This phase transition is spontaneous under conditions of supersaturation after crossing the nucleation barrier. Moreover, any protein sequence possesses the information necessary to adopt the amyloid conformation (cross-β), with no requirement for a protein seed/prion to act as a conformational template. In the current study, we show that HSV-1 and UV-inactivated SARS-CoV-2 catalyze amyloid aggregation of a multitude of proteins in their native environment and at their physiologic concentration in human CSF. This result further supports the notion that protein aggregation is a function of the recipient environment in terms of the concentration of specific proteins that is close to their limit of solubility (supersaturation) and their ability to interact with nucleating surfaces (26, 27, 40). Supersaturation provides the molecular proximity required to favor the generic intermolecular interactions necessary for amyloid formation over the specific intramolecular interactions required for native folding, with surfaces acting as nucleation sites that catalyze phase transition by lowering the interfacial energy barrier (21).

But which "viral surfaces"?!!!

Keep distancing, keep isolating, keep masking, keep handwashing.  Given a choice between infection or vaccination, vaccination is still a much better choice, since any mRNA vaccine will not proliferate within your body while teaching your immune system.  I want more details, though.  Which viral protein is dangerous?  And is this process in any way related to the syncytia capabilities of this virus?  I feel like we're on the verge of learning something immensely important.

Comments

[oracne]

That does sound like a breakthrough!

Getting my bivalent booster tomorrow.

[wispywillow]

The scary part of covid is how unknown it's been. Any breakthrough in knowledge will be wonderful and much needed!

[kathmandu]

Wow. That is intriguing.

There had been some speculation, Before, about herpes simplex maybe getting into the brain and causing the amyloid plaques and neurodegeneration of Alzheimer's dementia.

At the time I heard about it, researchers were having trouble getting projects approved because there wasn't enough already-existing evidence to justify looking for more. If all this investigation of Covid helps illuminate the mechanisms of Alzheimer's, that will be a silver lining.