Thread by @SoothSpider

#PRRARSV I felt like we talked about this nuclear localization signal (NLS) somewhere before, but with all the banned and deleted accounts... 😅

👀 @dr_SDRK @Alletwiederjut @NarfGb @Vonboo5 @NotJason666 @PinsolleT @AnneliseBocquet @PlanZip @TeamsforLife

frontiersin.org/articles/10.33…

" The translocation of the SARS-CoV-2 S mRNA appeared to be assisted by the S protein, which contains an NLS motif that is unique among human pathogenic beta-coronaviruses."

" To avoid image artifacts, we imaged multiple independent slides of SARS-CoV-2-infected airway ...

... epithelium (from three independent donors) using at least two different high-end confocal microscopes. Additionally, we used at least two different image processing strategies to determine nuclear localization. "

"Importantly, we were able to determine S mRNA nuclear translocation not only inside the nucleus but also on the nuclear surface."

"Interestingly, less than 10% of S mRNA was detected at the nuclear surface, which could explain the transitionary stage of S mRNA before it enters the nucleus or the novel transnuclear-membrane translocation of S mRNA, which was examined and described later."

" In approximately 1% of instances, S mRNA successfully translocated into the nucleus. The nuclear translocation of S mRNA is highly unusual because there have been few previous reports of S mRNA nuclear translocation and no information on the mechanism of nuclear translocation."

"However, we found that the IS4 “NSPR” created a pat7 NLS “PRRARSV” in the S protein, which was unique to SARS-CoV-2. Whether this noncanonical furin cleavage destroys the function of the NLS motif is important to determine, as the proposed noncanonical ...

... furin cleavage site is constitutively within the NLS motif (described later)."

🤔 So while other betacoronaviruses have NLSs, SC2 is the only one with it in the S-protein? That's part of the mRNA sequence in the vaccines?🤔

"Among coronaviruses, SARS-CoV-2 S protein is the first type-1 transmembrane glycoprotein that translocates into the nucleus."

"First, we investigated whether the proposed polybasic site “RRAR” could itself be an NLS motif."

"... but was part of the P7 “PRRARSV” NLS. Thus, the inserted sequence creates the NLS in the S protein of SC2 and may make SARS-CoV-2 unique among human pathogenic coronaviruses."

"When SARS-CoV-2 N protein has already been shown to bind to RNA (Schmidt et al., 2021), we still do not know how exactly S protein binds to S mRNA for nuclear translocation. "

"We only know is S mRNA nuclear translocation is more likely mediated by the S protein because S mRNA nuclear translocation was always associated with the S protein."

Fantastic! 😩 So the FCS could also have a 2nd function in binding to mRNA & translocating it into the nucleus.

"In conclusion, the SARS-CoV-2 S protein has a functional pat7 NLS “PRRARSV,” that results in one out of four S proteins translocating into the nucleus in infected cells. S Protein appears to shuttle S mRNA (possibly the genome) into the nucleus of the infected cells."

The real question is ... If this was true, do you think they knew that before using the entire sequence in the vaccines? 🤔

I guess this is the cue for the mRNA ➡️ cDNA thread/papers that show that indeed it reverse transcribes. @dr_SDRK