Gomaa Mostafa-Hedeab1,2. 1. Pharmacology department, Medical College, Jouf University, KSA. 2. Pharmacology department, Faculty of Medicine, Beni-Suef University, Egypt.
Abstract
BACKGROUND: Since its first appearance in December of 2019, regular updates around the world demonstrates that the number of new Corona Virus 2019 (COVID-19) cases are increasing rapidly, indicating that not only does COVID-19 exhibit a rapid spread pattern, but human intervention is necessary for its resolution. Up until today (27-5-2020) and according to the World Health Organization (WHO), the number of confirmed COVID-19 cases has surpassed 4.5 million with more than 307, 500 deaths. Almost all countries have been affected by COVID-19, and resultingly, various drug trials have been conducted, however, a targeted treatment remains to be made accessible to the public. Recently, Angiotensin-Converting Enzyme-2 (ACE2) has gained some attention for its discovery as a potential attachment target of COVID-19. METHODS: We reviewed the most recent evidence regarding ACE2 distribution and action, the binding mechanism of COVID-19 and its correlation to cellular injury, ACE2 polymorphisms and its association to fatal COVID-19 and susceptibility and, finally, current ACE2-based pharmacotherapies against COVID-19. RESULTS: Blocking the ACE2 receptor-binding domain (RBD) using a specific ligand can prevent COVID-19 from binding, and consequently cellular entry and injury. Comparatively, soluble ACE2, which has a higher affinity to COVID-19, can neutralize COVID-19 without affecting the homeostatic function of naturally occurring ACE2. Lastly, ACE2 mutations and their possible effect on the binding activity of COVID-19 may enable researchers to identify high-risk groups before they become exposed to COVID-19. CONCLUSION: ACE2 represents a promising target to attenuate or prevent COVID-19 associated cellular injury.
BACKGROUND: Since its first appearance in December of 2019, regular updates around the world demonstrates that the number of new Corona Virus 2019 (COVID-19) cases are increasing rapidly, indicating that not only does COVID-19 exhibit a rapid spread pattern, but human intervention is necessary for its resolution. Up until today (27-5-2020) and according to the World Health Organization (WHO), the number of confirmed COVID-19 cases has surpassed 4.5 million with more than 307, 500 deaths. Almost all countries have been affected by COVID-19, and resultingly, various drug trials have been conducted, however, a targeted treatment remains to be made accessible to the public. Recently, Angiotensin-Converting Enzyme-2 (ACE2) has gained some attention for its discovery as a potential attachment target of COVID-19. METHODS: We reviewed the most recent evidence regarding ACE2 distribution and action, the binding mechanism of COVID-19 and its correlation to cellular injury, ACE2 polymorphisms and its association to fatal COVID-19 and susceptibility and, finally, current ACE2-based pharmacotherapies against COVID-19. RESULTS: Blocking the ACE2 receptor-binding domain (RBD) using a specific ligand can prevent COVID-19 from binding, and consequently cellular entry and injury. Comparatively, soluble ACE2, which has a higher affinity to COVID-19, can neutralize COVID-19 without affecting the homeostatic function of naturally occurring ACE2. Lastly, ACE2 mutations and their possible effect on the binding activity of COVID-19 may enable researchers to identify high-risk groups before they become exposed to COVID-19. CONCLUSION: ACE2 represents a promising target to attenuate or prevent COVID-19 associated cellular injury.
Authors: Carlos Díez-Freire; Jorge Vázquez; María F Correa de Adjounian; Merari F R Ferrari; Lihui Yuan; Xeve Silver; Raquel Torres; Mohan K Raizada Journal: Physiol Genomics Date: 2006-06-20 Impact factor: 3.107
Authors: Herbert L Jackman; Malek G Massad; Marin Sekosan; Fulong Tan; Viktor Brovkovych; Branislav M Marcic; Ervin G Erdös Journal: Hypertension Date: 2002-05 Impact factor: 10.190
Authors: Heather N Reich; Gavin Y Oudit; Josef M Penninger; James W Scholey; Andrew M Herzenberg Journal: Kidney Int Date: 2008-10-01 Impact factor: 10.612
Authors: V Stalin Raj; Huihui Mou; Saskia L Smits; Dick H W Dekkers; Marcel A Müller; Ronald Dijkman; Doreen Muth; Jeroen A A Demmers; Ali Zaki; Ron A M Fouchier; Volker Thiel; Christian Drosten; Peter J M Rottier; Albert D M E Osterhaus; Berend Jan Bosch; Bart L Haagmans Journal: Nature Date: 2013-03-14 Impact factor: 49.962
Authors: Gabriel Augusto Pires de Souza; Ikram Omar Osman; Marion Le Bideau; Jean-Pierre Baudoin; Rita Jaafar; Christian Devaux; Bernard La Scola Journal: Front Cell Infect Microbiol Date: 2021-06-11 Impact factor: 5.293