SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming.
The site of the Transmembrane protease, serine 2 gene is on 21q22.3. People with down syndrome have 3 of the 21th chromosome. Regarding to other virus, we know from an earlier work, that trisomic patients showed more than a twofold increase in sensitivity to herpes simplex virus as compared to controls.
I wold like to ask:
Are people with higher TMPRSS2 expresson level, for example ones with Down syndrome suscepteble to COVID-19?
Agnes Pataki,
Logically speaking, "Yes" would be the immediate answer that comes to mind.
Weirdly enough, the expression levels of TMPRSS2 seem to be relatively low in the lung tissue when compared to other soft issue, according to the following article:
http://www.chinaxiv.org/abs/202002.00062
If we looked at Figure S5 over at page 33(/34) we can see that the expression levels of TMPRSS2 are relatively low, which doesn't correlate with the degree of damage the virus is known to cause to lung tissue.
Hope that helps!
Agnes Pataki
Unfortunately the relatively higher levels of TMPRSS2 are related with SARS-CoV-2 infection since this protease is determinant for virus entry. Please see: 1) Hatesuer et al, 2013. Tmprss2 Is Essential for Influenza H1N1 Virus Pathogenesis in Mice. PlosOne.
2) Hoffman et al, 2020. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell.
Cheers,
Yes... probabilities are there...Drug which acts through this pathway is Camostat Mesylate... which is under trial against COVID-19....
So it’s scope as prophylactic therapy is still unknown....
great topic!!
I think the ratio of TEMPRESS and ACE2 is the matter, besides, I read somewhere that there are some other receptors and even priming enzymes in the potential of the same duty.
so it seems the virus entry is much complex than a straight line of causality.
BEst
These papers could add some evidence to the topic.
1) Shereen et al (2020). COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses. J Adv Res.
2) Hoffmann et al (2020). SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell.
3) Iwata-Yoshikawa et al (2019). TMPRSS2 Contributes to Virus Spread and Immunopathology in the Airways of Murine Models after Coronavirus Infection. J Virol.
4) Li et al (2003). Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature.
Cheers,
Firas Khalil Khana - Thanks for the information, and for the Canrong article about Furin. Yes, it helps a lot! It seems to be another way for cell entry of coronaviruses.
Gustavo Casimiro - Thank you for all the the links and for your help. I havn’t finished reading yet. 😊
Pejman Abbasi - Thanks for the reply. I agree that the ratio of TEMPRESS to ACE2 is important, and I know, there are other priming enzymes, such as furin or furin-like proteases, as Firas Khalil Khana suggested in this conversation, but I find only one docking receptor: ACE2 for SARS-CoV-2. It may be interesting because a few percent of people seem to be resistant. The reason for this can be genetic as well.
Rituja Kaushal - Thank you for bringing this existing Japanese drug to my attention, trade name: Foipan, a TMPRSS2 inhibitor.. This was the same drug which was used to prove the entering mechanism of SARS-CoV-2 ! 😊 I just read it in a Hoffman article, what Gustavo Casimiro mentioned.
Thank you all for yor help!
Abbas Rahdar, thank you for your article. It is a valuable work, helps me a lot.
You will find the attached article interesting.
Article SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed...
You may find this article interesting https://www.sciencedirect.com/science/article/pii/S2666379120300240
Firzan Nainu, thank you very much, I find it interesting very much. :)
This question seems to be more complex, as I thought first time. Though they didn't examine the role of TMPRSS2, they find a row of other genes on chromosome 21 influencing COVID-19. Thank you for this link.