Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity(science.sciencemag.org)
science.sciencemag.org
Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity
https://science.sciencemag.org/content/early/2020/10/19/science.abd2985
13 comments
The concluding paragraph of the originally linked Science paper is revealing:
> There is limited knowledge about the virus-host interactions that determine cellular entry of SARS-CoV-2. Viruses display considerable redundancy and flexibility because they can exploit weak multivalent interactions to enhance affinity. While the focus to date has been almost entirely on the role of ACE2 in SARS-CoV-2 entry, the expression pattern of ACE2 does not match tissue tropism of SARS-CoV-2. This raises the possibility that co-factors are required to facilitate virus-host cell interactions in cells with low ACE2 expression. NRP1 could represent such an ACE2 potentiating factor; however, it is also possible that SARS-CoV-2 can enter cells independently of ACE2 when viral loads are high. The reason why a number of viruses use NRPs as entry factors could be because of their high expression on epithelia facing the external environment, and their function in enabling cell, vascular, and tissue penetration.
NRP1 might explain some of the strange pathophysiology of COVID-19.
[1] https://en.wikipedia.org/wiki/Coronavirus_disease_2019#Patho...
> There is limited knowledge about the virus-host interactions that determine cellular entry of SARS-CoV-2. Viruses display considerable redundancy and flexibility because they can exploit weak multivalent interactions to enhance affinity. While the focus to date has been almost entirely on the role of ACE2 in SARS-CoV-2 entry, the expression pattern of ACE2 does not match tissue tropism of SARS-CoV-2. This raises the possibility that co-factors are required to facilitate virus-host cell interactions in cells with low ACE2 expression. NRP1 could represent such an ACE2 potentiating factor; however, it is also possible that SARS-CoV-2 can enter cells independently of ACE2 when viral loads are high. The reason why a number of viruses use NRPs as entry factors could be because of their high expression on epithelia facing the external environment, and their function in enabling cell, vascular, and tissue penetration.
NRP1 might explain some of the strange pathophysiology of COVID-19.
[1] https://en.wikipedia.org/wiki/Coronavirus_disease_2019#Patho...
Papers like this remind me how insanely complicated biological systems are; it's amazing how much work has to go into identifying something like this.
Hope this and other research yield some effective methods for treating the virus.
Hope this and other research yield some effective methods for treating the virus.
I see biology as some sort of alien technology we have been trying to reverse engineer but still have a long ways to go before fully understanding it. It's literally everywhere, we are made up of it, but we still can't figure it out.
Despite a foray into chemistry in my past I find this article prohibitively difficult to fully internalize beyond a superficial understanding and I would really appreciate it if someone in the field could explain what the study shows.
The most important thing in biology/biochemistry to realize is that everything that happens requires things to bump into each other, many times, randomly. If things fit/stick to each other really well (think lock and key fitting, glove to hand idea), they only need to bump into each other a couple time before they lock together. This study shows that a thing on the virus sticks to a thing on a cell (Neuropillin-1) really well. What this does is then keep the virus really close to the cell so it can bump into the other thing (ACE2) more often. This is important because ACE2 is how the virus gets into the cell. So the first thing (Neuropillin-1 binding) sticks the virus to the cell and gives it more time to find the entry switch (ACE2). Without that first binding (from Neuropillin-1), the number of times the virus bumps into ACE2 is not a lot because there isn't much of it on the cells.
The spike of the SARS-CoV-2 virus binds to the neuropilin-1 (NRP1) [1] cell receptor in addition to ACE2 [2].
[1] https://en.wikipedia.org/wiki/Neuropilin_1#Role_in_COVID-19
[2] https://en.wikipedia.org/wiki/Angiotensin-converting_enzyme_...
[1] https://en.wikipedia.org/wiki/Neuropilin_1#Role_in_COVID-19
[2] https://en.wikipedia.org/wiki/Angiotensin-converting_enzyme_...
Was Covid-19 a work-in-progress therapy for cancer treatment? Cancer cells (especially metastatic) have an overexpression of NRP1 (Neuropilin-1). Covid-19 will try to invade NRP1 over-expressing cells and try to destroy them, and hence help with destroying cancerous cells. Am I wrong?
https://scholar.google.ch/scholar?hl=en&as_sdt=0%2C5&as_vis=...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515012/
https://scholar.google.ch/scholar?hl=en&as_sdt=0%2C5&as_vis=...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515012/
[deleted]
Neuropilin 1 is associated with cells in veins and arteries. This study was probably a focus due to the fact that COVID-19 tends to cause vascular issues.
Engineering for that would be unwise in a viral treatment due to the fact you can't control dosage enough to keep it from killing the patient by turning their arteries to jello.
Engineering for that would be unwise in a viral treatment due to the fact you can't control dosage enough to keep it from killing the patient by turning their arteries to jello.
"Such C-terminal sequences that conform to the “C-end rule” (CendR) are known to bind to and activate neuropilin (NRP1 and NRP2) receptors at the cell surface."
Sounds like we should add a CendR-cleaved S-protein to our vaccines...
Sounds like we should add a CendR-cleaved S-protein to our vaccines...
[1] https://journals.lww.com/pain/Abstract/9000/SARS_CoV_2_Spike...
[2] https://youtu.be/8vV3TWtLXnQ?t=3883