Could a specific ACE2 activator drug improve the clinical outcome of SARS-CoV-2? A potential pharmacological insight

References

• Li W, Moore MJ, Vasilieva N, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426:450–454.
   PubMed Web of Science ®Google Scholar
• Prabakaran P, Xiao X, Dimitrov DS. A model of the ACE2 structure and function as a SARS-CoV receptor. Biochem Biophys Res Commun. 2004;314:235–241.
   PubMed Web of Science ®Google Scholar
• Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:271–280.
   PubMed Web of Science ®Google Scholar
• Heurich A, Hofmann-Winkler H, Gierer S, et al. TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein. J Virol. 2014;88:1293–1307.
   PubMed Web of Science ®Google Scholar
• Lambert DW, Yarski M, Warner FJ, et al. Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARSCoV) receptor, angiotensin-converting enzyme-2 (ACE2). J Biol Chem. 2005;280:30113–30119.
   PubMed Web of Science ®Google Scholar
• Haga S, Nagata N, Okamura T, et al. TACE antagonists blocking ACE2 shedding caused by the spike protein of SARS-CoV are candidate antiviral compounds. Antiviral Res. 2010;85:551–555.
   PubMed Web of Science ®Google Scholar
• Glowacka I, Bertram S, Muller MA, et al. Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response. J Virol. 2011;85:4122–4134.
   PubMed Web of Science ®Google Scholar
• Imai Y, Kuba K, Penninger JM. Angiotensin-converting enzyme 2 in acute respiratory distress syndrome. Cell Mol Life Sci. 2007;64:2006–2012.
   PubMed Web of Science ®Google Scholar
• Meng J, Xiao G, Zhang J, et al. Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension. Emerg Microbes Infect. 2020;9(1):757‐760.
   Web of Science ®Google Scholar
• Danser JAH, Epstein M, Batlle D. Renin-angiotensin system blockers and the COVID-19 pandemic - At present there is no evidence to abandon renin- angiotensin system blockers. Hypertension. 2020;75. DOI:https://doi.org/10.1161/HYPERTENSIONAHA.120.15082
   Google Scholar
• Khashkhusha TR, Chan JSK, Harky A. ACE inhibitors and COVID-19: we don’t know yet. J Card Surg. 2020;35(6):1172–1173.
   PubMed Web of Science ®Google Scholar
• Wang PH, Cheng Y. Increasing host cellular receptor—angiotensin-converting enzyme 2 (ACE2) expression by coronavirus may facilitate 2019-nCoV infection. bioRxiv. 2020;1–22. DOI:https://doi.org/10.1101/2020.02.24.963348
   Google Scholar
• Kuba K, Imai Y, Rao S, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. 2005;11(8):875‐879. .
   PubMed Web of Science ®Google Scholar
• Nicolau LAD, PJC M, Vale ML. What would Sérgio Ferreira say to your physician in this war against COVID-19: how about kallikrein/kinin system? Med Hypotheses. 2020;143(109886):1–7.
   Google Scholar
• Hamming I, Timens W, Bulthuis ML, et al. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203:631–637.
   PubMed Web of Science ®Google Scholar
• Zaim S, Chong JH, Sankaranarayanan V, et al. COVID-19 and multiorgan response. Curr Probl Cardiol. 2020;45(8):100618.
   PubMed Web of Science ®Google Scholar
• Yang XH, Deng W, Tong Z, et al. Mice transgenic for human angiotensin-converting enzyme 2 provide a model for SARS coronavirus infection. Comp Med. 2007;57(5):450–459.
   PubMed Web of Science ®Google Scholar
• Chakraborty C, Sharma AR, Sharma G, et al. SARS-CoV-2 causing pneumonia-associated respiratory disorder (COVID-19): diagnostic and proposed therapeutic options. Eur Rev Med Pharmacol Sci. 2020;24(7):4016–4026.
   PubMed Web of Science ®Google Scholar
• Saha A, Sharma AR, Bhattacharya M, et al. Probable Molecular Mechanism of Remdesivir for the Treatment of COVID-19: need to Know More [published online ahead of print, 2020 May 12]. Arch Med Res. 2020;30699-8:S0188-4409(20).
   Google Scholar
• Mahase E. Covid-19: demand for dexamethasone surges as RECOVERY trial publishes preprint. BMJ. 2020;369:m2512.
   PubMedGoogle Scholar
• Bhattacharya M, Sharma AR, Patra P, et al. Development of epitope-based peptide vaccine against novel coronavirus 2019 (SARS-COV-2): immunoinformatics approach. J Med Virol. 2020;92(6):618–631.
   PubMed Web of Science ®Google Scholar
• Oliveira GLS, Freitas RM. Diminazene aceturate - an antiparasitic drug of antiquity: advances in pharmacology & therapeutics. Pharmacol Res. 2015;102:138–157.
   PubMed Web of Science ®Google Scholar
• Kulemina LV, Ostrov DA. Prediction of off-target effects on angiotensin converting enzyme 2. J Biomol Screen. 2011;16:878–885.
   PubMedGoogle Scholar
• Peregrine AS, Mamman M. Pharmacology of diminazene: a review. Acta Trop. 1993;54:185–203.
   PubMed Web of Science ®Google Scholar
• Rodrigues-Prestes TR, Rocha NP, Miranda AS, et al. The anti-inflammatory potential of ACE2/Angiotensin-(1-7)/Mas receptor axis: evidence from basic and clinical research. Curr Drug Targets. 2017;18:1301–1313.
   PubMed Web of Science ®Google Scholar
• Rajapaksha IG, Mak KY, Huang P, et al. The small molecule drug diminazene aceturate inhibits liver injury and biliary fibrosis in mice. Sci Rep. 2018;8(10175):1–14.
   PubMedGoogle Scholar
• Fang Y, Gao F, Liu Z Angiotensin-converting enzyme 2 attenuates inflammatory response and oxidative stress in hyperoxic lung injury by regulating NF-κB and Nrf2 pathways. QJM. 2019;112(12):914–924. https://doi.org/https://doi.org/10.1093/qjmed/hcz206
   PubMed Web of Science ®Google Scholar
• Imai Y, Kuba Y, Rao S, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005;436:112–116.
   PubMed Web of Science ®Google Scholar
• Ding Y, He L, Zhang Q, et al. Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways. J Pathol. 2004;203:622–630..
   PubMed Web of Science ®Google Scholar
• Liang W, Feng Z, Rao S, et al. Diarrhoea may be underestimated: a missing link in 2019 novel coronavirus. Gut. 2020;1–3. DOI:https://doi.org/10.1136/gutjnl-2020-320832.
   Google Scholar
• Li B, Yang J, Zhao F, et al. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin Res Cardiol. 2020;109(5):531–538.
   PubMed Web of Science ®Google Scholar
• Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395:1033–1034.
   PubMed Web of Science ®Google Scholar
• Strabelli TMV, Uip DE. COVID-19 and the heart. Arq Bras Cardiol. 2020. DOI:https://doi.org/10.36660/abc.20200209
   Google Scholar
• Xu L, Liu J, Lu M, et al. Liver injury during highly pathogenic human coronavirus infections. Liver Int. 2020;40(5):998–1004.
   PubMed Web of Science ®Google Scholar
• Velkoska E, Patel SK, Griggs K, et al. Diminazene aceturate improves cardiac fibrosis and diastolic dysfunction in rats with kidney disease. PLoS One. 2016;11:1–15.
   Web of Science ®Google Scholar
• Cheng H, Wang Y, Wang GQ. Organ-protective effect of angiotensin-converting enzyme 2 and its effect on the prognosis of COVID-19. J Med Virol. 2020;1–5. DOI:https://doi.org/10.1002/jmv.25785
   Google Scholar
• Qaradakhi T, Gadanec LK, McSweeney KR, et al. The potential actions of angiotensin-converting enzyme II (ACE2) activator diminazene aceturate (DIZE) in various diseases. Clin Exp Pharmacol Physiol. 2020;47:751–758.
   PubMed Web of Science ®Google Scholar