This concept note was written by Dr. Catherine Poisson-Benatouil, Anesthesiologist - Intensive Care Physician, and revised by the consultant Jean-Luc Galabert.
Dr. Catherine Poisson-Benatouil
Anesthesiologist - Intensive Care Physician
Maison de l’Artemisia de Pointe-Noire | Republic of Congo
contact@maison-artemisia.org
Jean-Luc Galabert
Consultant
Inter-Culturel design and project management office | Nyamata - Rwanda
etudes@inter-culturel.net
Abstract
As early as 2011 for SARS-CoV-2003, it was noted that when a target cell expresses two receptors on its surface (such as type II pneumocytes), on the one hand the angiotensin converting enzyme type 2 (ACE2) receptor, a zinc metalloprotease, and on the other hand the transmembrane serine protease TMPRSS2 (TMPRSS2), it is more likely to be infected. Membrane expression of TMPRSS2 is known in the literature to be stimulated by androgen receptor (AR) expression on the cell surface. AR are expressed by the stimulation of androgens (A). For SARS-CoV-2, it has been shown that its cellular entry is blocked by a specific TMPRSS2 protease inhibitor. The first step for cell entry is therefore the AR activation of TMPRSS2 expression on the membrane surface of target cells that may possess both ACE2 and TMPRSS2 receptors. The initial priming of the S protein, spike protein, of the SARS-CoV-2 virus, is made on the expressed protease. Then, once priming is complete, the serine protease can cause cleavage of the ACE2 receptor present and thus increase the entry of the virus into the cell. Androgen expression of AR and therefore TMPRSS2 is known to occur in cells of the lung, prostate, gastrointestinal tract and upper airways and in certain cancerous prostate and lung tissues. This activation chain is particularly evident in tumor cells and metastatic cancers that are resistant to hormone therapy. Artemisinin, its derivatives and Artemisia annua have demonstrated their efficacy in inhibiting the growth of tumor and metastatic prostate cancer cells in vitro, in vivo and clinically in humans. Their action involves a decrease in AR expression and subsequently of TMPRSS2 involved in the diffusion of biochemical cellular messages stimulating the appearance of tumor and metastatic cells of the prostate. If artemisinin and its derivatives of Artemisia annua have this inhibitory capacity via AR on TMPRSS2 in prostate cancer, they could similarly have it on cells infected with SARS-CoV-2 and thus inhibit the initial priming of the viral S protein which is the first key to the stimulation of the ACE2 receptor and intracellular viral penetration.
25/05/2020
https://lavierebelle.org/protease-serique-transmembranaire