Combination of Angiotensin (1-7) Agonists and Convalescent Plasma as a New Strategy to Overcome Angiotensin Converting Enzyme 2 (ACE2) Inhibition for the Treatment of COVID-19

Frontiers in Medicine

Ali H. Eid¹  Firas Kobeissy²  Ali Nehme³  Bassam Berry⁴  Hussein Karaki⁵  Sarah Mantash⁵  Kazem Zibara⁵  Rawan Hallal⁵  Rawan Nehme⁵  Hawraa Issa⁶  Kawthar Dhayni⁷  Wissam H. Faour⁸  Abbas Khosravi⁹  Vahideh Takhviji⁹ 

[1] Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, Qatar;Biomedical and Pharmaceutical Research Unit, QU Health, Qatar University, Doha, Qatar;Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon;Department of Human Genetics, McGill University, Montreal, QC, Canada;Institut Pasteur, Paris 6 University, Paris, France;PRASE and Biology Department, Faculty of Sciences - I, Lebanese University, Beirut, Lebanon;PRASE and Biology Department, Faculty of Sciences - I, Lebanese University, Beirut, Lebanon;College of Public Health, Phoenicia University, Zahrani, Lebanon;PRASE and Biology Department, Faculty of Sciences - I, Lebanese University, Beirut, Lebanon;EA7517, MP3CV, CURS, University of Picardie Jules Verne, Amiens, France;School of Medicine, Lebanese American University, Byblos, Lebanon;Transfusion Research Center, High Institute for Research and Education in Transfusion, Tehran, Iran;

关键词: ACE2;    SARS-CoV-2;    COVID-19;    lung pathology;    cardiovascular pathology;    convalescent plasma (CP);    Angiotensin 1-7 (Ang1-7);    combination therapy;   

DOI  :  10.3389/fmed.2021.620990

来源: Frontiers

【 摘 要 】

Coronavirus disease-2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the most concerning health problem worldwide. SARS-CoV-2 infects cells by binding to angiotensin-converting enzyme 2 (ACE2). It is believed that the differential response to SARS-CoV-2 is correlated with the differential expression of ACE2. Several reports proposed the use of ACE2 pharmacological inhibitors and ACE2 antibodies to block viral entry. However, ACE2 inhibition is associated with lung and cardiovascular pathology and would probably increase the pathogenesis of COVID-19. Therefore, utilizing ACE2 soluble analogs to block viral entry while rescuing ACE2 activity has been proposed. Despite their protective effects, such analogs can form a circulating reservoir of the virus, thus accelerating its spread in the body. Levels of ACE2 are reduced following viral infection, possibly due to increased viral entry and lysis of ACE2 positive cells. Downregulation of ACE2/Ang (1-7) axis is associated with Ang II upregulation. Of note, while Ang (1-7) exerts protective effects on the lung and cardiovasculature, Ang II elicits pro-inflammatory and pro-fibrotic detrimental effects by binding to the angiotensin type 1 receptor (AT1R). Indeed, AT1R blockers (ARBs) can alleviate the harmful effects associated with Ang II upregulation while increasing ACE2 expression and thus the risk of viral infection. Therefore, Ang (1-7) agonists seem to be a better treatment option. Another approach is the transfusion of convalescent plasma from recovered patients with deteriorated symptoms. Indeed, this appears to be promising due to the neutralizing capacity of anti-COVID-19 antibodies. In light of these considerations, we encourage the adoption of Ang (1-7) agonists and convalescent plasma conjugated therapy for the treatment of COVID-19 patients. This therapeutic regimen is expected to be a safer choice since it possesses the proven ability to neutralize the virus while ensuring lung and cardiovascular protection through modulation of the inflammatory response.

【 授权许可】

CC BY