The binding site and entry-point for SARS-CoV2 is angiotensin-converting enzyme 2(ACE2), which is highly expressed in the respiratory epithelial cells, lymphocytes, endothelial cell, and renal tubular epithelial cells.
Research agrees that sex and gender may affect the intensity of covid 19.
The infection rate and severity of covid19 vary from country to country and from city to city.
Some studies link this to mutation in covid 19, but there may be synergy with the type ( polymorphism ) of ACE2 receptors as you assume above .
Hi Hayder Al-kuraishy,
Here, I would like to answer some things here in a brief and appropriate way.
Polymorphism has been reported to effect the susceptibility to SARS COV2.
Firstly, Polymorphism of ACE2 was reported in the Chinese population with three variants (i.e. ACE2 rs4240157, rs4646155 and rs4830542). Such variation may also occur due to some drugs intake, like Malard L. et al. In 2013 reported the fact that; Nicotine dependence in Canadian teens leads to the occurrence of another three different variants of ACE2 (rs2074192,rs233575 and rs2158083). And If we analyse these things according to the recent works, a soluble form of ACE2 (that lacks the transmembrane and cytoplasmic domain of molecule) has capability to block the SARS spike protein binding to the its respective receptor. Other side the research done by Xiao et al. In 2014, suggests that the point mutation Leucine at position 544 with alanine in ACE2, facilitate the SARS COV entry into cells.
*Now, I would like to place some aspects of other treatments that could increase the susceptibility of SARS COV-2 in terms of infection.
By the affect of S protein on the ACE2 receptor, it may result in increased levels of Angiotensin-II levels which could cause hypertension (HT). If we carryout the treatment of HT, like olmesartan (ARB) treatment, the it increases the urinary ACE2 levels (reported by Furushi M et al. 2015) and by taking ACE-inhibitors (ACEi), it can cause increased intestinal ACE2 mRNA expression. There are other aspects like presence of more genes codes for ACE2 protein in males than females is major factor to cause higher levels of ACE2 in male respiratory system (mainly lungs) than female which ultimately mediates the high risk or infectivity in males.
I hope this will help you to remove your doubts.
Thank you.
Regards,
Gaurav.
Theoratically polymorphism may have impact on susceptibility of COVID-19 but need studies before final conclusion.
very good response Gaurav,
however does ACE2 inhibitors like valproic acid or azathioprine prevent COVID-19?
Dear Hayder Al-kuraishy,
The medications which you mentioned here, only Valproic acid has been taken into the consideration for the further usage to treat Covid19 (As it's a fatty acid derivative). A leading scientist (Neel Sarovar Bhavesh) at "International Center for Genetic engineering and Biotechnology (ICGEB), New delhi (India), has purposed the use of Valproic acid as a drug to treat Covid19 virus by performing molecular binding simulation and energy calculation. Therefore he has implemented that "valproic acid Co~A"can inhibit the RNA dependent RNA Polymerase (RdRp) which shows further perspective to get used in the test studies. Other side, azathioprine has not reported to show some possibility to treat the SARS COV2 virus. As it's an immunosuppressive drug.
i so appreciate your elegant response , please add more informations