ACE2: The Major Cell Entry Receptor for SARS-CoV-2
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STATE OF THE ART REVIEW
ACE2: The Major Cell Entry Receptor for SARS‑CoV‑2 Filippo Scialo1,4 · Aurora Daniele2,4 · Felice Amato3,4 · Lucio Pastore3,4 · Maria Gabriella Matera5 · Mario Cazzola6 · Giuseppe Castaldo3,4 · Andrea Bianco1 Received: 15 September 2020 / Accepted: 5 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Despite the unprecedented effort of the scientific community, the novel SARS-CoV-2 virus has infected more than 46 million people worldwide, killing over one million two hundred thousand. Understanding the mechanisms by which some individuals are more susceptible to SARS-CoV-2 infection and why a subgroup of them are prone to experience severe pneumonia, and death should lead to a better approach and more effective treatments for COVID-19. Here, we focus our attention on ACE2, a primary receptor of SARS-CoV-2. We will discuss its biology, tissue expression, and post-translational regulation that determine its potential to be employed by SARS-CoV-2 for cell entry. Particular attention will be given to how the ACE2 soluble form can have a great impact on disease progression and thus be used in a potential therapeutic strategy. Furthermore, we will discuss repercussions that SARS-CoV-2/ACE2 binding has on the renin–angiotensin system and beyond. Indeed, although mostly neglected, ACE2 can also act on [des-Arg 937]-bradykinin of the kinin–kallikrein system regulating coagulation and inflammation. Thorough comprehension of the role that ACE2 plays in different pathways will be the key to assess the impact that SARS-CoV-2/ACE2 binding has on organismal physiology and will help us to find better therapies and diagnostic tools. Keywords SARS-CoV-2 · ACE2 receptor · COVID-19
Introduction In the last 20 years, humanity has witnessed an increasing number of pandemics that have hospitalized or killed hundreds of thousands of people, leaving our healthcare systems under unprecedented pressure. Severe acute respiratory syndrome (SARS) in 2002 and Middle East respiratory syndrome in 2012 (MERS) [1], and more recently the novel * Mario Cazzola [email protected] 1
Dipartimento di Scienze Mediche Traslazionali, University of Campania “L. Vanvitelli”, Naples, Italy
2
Dipartimento di Scienze e Tecnologie Ambientali Biologiche Farmaceutiche, University of Campania “L. Vanvitelli”, Naples, Italy
3
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università Di Napoli Federico II, Naples, Italy
4
CEINGE, Biotecnologie Avanzate, Naples, Italy
5
Dipartimento di Medicina Sperimentale, University of Campania “L. Vanvitelli”, Naples, Italy
6
Dipartimento di Medicina Sperimentale, University of Rome “Tor Vergata”, Rome, Italy
infection named COVID-19, detected in Wuhan China in 2019 are caused by closely related coronaviruses, SARSCoV, MERS-CoV and SARS-CoV-2, respectively [2]. Their unexpected and periodic appearance combined with a high level of human-to-human transmission has made coronaviruses a threat to our societies and economies,
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