/sci/ - Science & Math » Thread #11545654

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Restoring innate immune response in coronavirus infected cells

Anonymous Wed 08 Apr 21:13:14 2020 No.11545654 View Reply Original Report

Quoted By: >>11545659 >>11545664 >>11545673 >>11545708 >>11545742

Potential therapies to restore STAT1 signaling in coronavirus infected cells

1. upregulate KPNA ,

2. maybe we can trick the virus into binding something similiar to KPNA or can unhook the subunit required for translocation of stat1

Anonymous

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Anonymous Wed 08 Apr 2020 21:14:32 No.11545659 Report

Quoted By:

>>11545654
These drugs target karyopherin subunits -- maybe they will also bind to viral protein ORF6 -- or compete with the same binding site

(or it could make it much worse and supress stat 1 and mimic a high viral load)

Anonymous

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Anonymous Wed 08 Apr 2020 21:16:29 No.11545664 Report

Quoted By:

>>11545654
Here is another peptide that also modulates KPNA

(potential worrying to give someone chemo drugs to treat this and would only work if it can still allow translocation of the transcription factors)

But it seems easier than upregulating KPNA gene somehow and basicailly compensating for the inhibition of STAT

Anonymous

Anonymous Wed 08 Apr 2020 21:19:02 No.11545673 Report

Quoted By: >>11545683

>>11545654
https://blast.ncbi.nlm.nih.gov/Blast.cgi#A2RTY3

here is my blast query of all the proteins that overlap with KPNA also -- maybe we could upregulate one of these and get the virus to bind it instead of KPNA

Anonymous

Anonymous Wed 08 Apr 2020 21:21:50 No.11545683 Report

Quoted By:

>>11545673
>https://blast.ncbi.nlm.nih.gov/Blast.cgi#A2RTY3

wont let me save it for some reason . i just ran a blast for ref|NP_001307540.1

ran both
deltablast and psi

Anonymous

Anonymous Wed 08 Apr 2020 21:28:55 No.11545708 Report

Quoted By:

>>11545654
or what if you targeted the importin and exportin proteins that coronavirus uses?

Anonymous

Anonymous Wed 08 Apr 2020 21:38:35 No.11545742 Report

Quoted By:

>>11545654
Great thread OP. My background is in innate immunity so it's cool to see some threads on it once in awhile.

This is a pretty neat paper. For anyone who's reading this thread and wants a tl;dr: the virus that caused SARS basically has a built-in protein that acts as a selective inhibitor for the innate anti-viral response in human cells. It's highly specific for a protein that is necessary for STAT1 to move to the nucleus and induce antiviral effector genes.

They were able to find a short C-terminal mutation that causes loss-of-function in ORF6, so maybe a chemist could make some kind of small molecule with specificity to just those residues.

Anonymous

Anonymous Wed 08 Apr 2020 21:39:22 No.11545746 Report

Quoted By: >>11545779

Samefag everywhere.
But still, that's SARS-nCoV, not SARS-nCoV-2.

Anonymous

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Anonymous Wed 08 Apr 2020 21:44:26 No.11545779 Report

Quoted By:

>>11545746

this is all i can find about sars-ncov-2 in relation to orf6

> SARS-CoV-2 sensitive to type I interferon pretreatment.

https://www.biorxiv.org/content/10.1101/2020.03.07.982264v1.full.pdf

-----------------------

Also this is an intresting paper from 2019

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537279/

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