Angiotensin-converting enzyme 2 (ACE2) receptor and SARS-CoV-2: Potential therapeutic targeting

doi:10.1016/j.ejphar.2020.173455

Review

. 2020 Oct 5:884:173455.

doi: 10.1016/j.ejphar.2020.173455. Epub 2020 Jul 31.

Angiotensin-converting enzyme 2 (ACE2) receptor and SARS-CoV-2: Potential therapeutic targeting

Sourena Sharifkashani¹, Melika Arab Bafrani², Alireza Soltani Khaboushan¹, Marzieh Pirzadeh³, Ali Kheirandish⁴, Hanie Yavarpour Bali³, Amirhossein Hessami⁵, Amene Saghazadeh⁶, Nima Rezaei⁷

Affiliations

¹ Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran; School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
² Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran; Students' Scientific Research Center (SSRC), Tehran University of Medical Sciences, Tehran, Iran.
³ Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran; Student Research Committee, Babol University of Medical Sciences, Babol, Iran.
⁴ Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran; Student Research Committee, School of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
⁵ Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran; Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
⁶ Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran; Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
⁷ Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran. Electronic address: rezaei_nima@tums.ac.ir.

PMID: 32745604
PMCID: PMC7834210
DOI: 10.1016/j.ejphar.2020.173455

Review

Angiotensin-converting enzyme 2 (ACE2) receptor and SARS-CoV-2: Potential therapeutic targeting

Sourena Sharifkashani et al. Eur J Pharmacol. 2020.

. 2020 Oct 5:884:173455.

doi: 10.1016/j.ejphar.2020.173455. Epub 2020 Jul 31.

Authors

Affiliations

¹ Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran; School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
² Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran; Students' Scientific Research Center (SSRC), Tehran University of Medical Sciences, Tehran, Iran.
³ Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran; Student Research Committee, Babol University of Medical Sciences, Babol, Iran.
⁴ Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran; Student Research Committee, School of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
⁵ Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran; Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
⁶ Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran; Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
⁷ Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran. Electronic address: rezaei_nima@tums.ac.ir.

PMID: 32745604
PMCID: PMC7834210
DOI: 10.1016/j.ejphar.2020.173455

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a beta coronavirus that uses the human angiotensin-converting enzyme 2 (ACE2) receptor as a point of entry. The present review discusses the origin and structure of the virus and its mechanism of cell entry followed by the therapeutic potentials of strategies directed towards SARS-CoV2-ACE2 binding, the renin-angiotensin system, and the kinin-kallikrein system. SARS-CoV2-ACE2 binding-directed approaches mainly consist of targeting receptor binding domain, ACE2 blockers, soluble ACE2, and host protease inhibitors. In conclusion, blocking or manipulating the SARS-CoV2-ACE2 binding interface perhaps offers the best tactic against the virus that should be treated as a fundamental subject of future research.

Keywords: ACE2; COVID-19; Origin; SARS-CoV2; Therapeutic; Transmission.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

**Fig. 1**
The interaction between SARS-CoV-2 S protein and membrane ACE2.

**Fig. 2**
Different therapeutic strategies directed towards SARS-CoV-2 binding to membrane ACE2.

See this image and copyright information in PMC

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References

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[1] Abelous J. Les substances hypotensives de l'urine humaine normale. CR Soc Biol. 1909;66:511–512.

[2] Abelous J. Les substances hypotensives de l'urine humaine normale. CR Soc Biol. 1909;66:511–512.

[3] Andersen K.G., Rambaut A., Lipkin W.I., Holmes E.C., Garry R.F. The proximal origin of SARS-CoV-2. Nat. Med. 2020;26:450–452. - PMC - PubMed

[4] Andersen K.G., Rambaut A., Lipkin W.I., Holmes E.C., Garry R.F. The proximal origin of SARS-CoV-2. Nat. Med. 2020;26:450–452. - PMC - PubMed

[5] Babcock G.J., Esshaki D.J., Thomas W.D., Ambrosino D.M. Amino acids 270 to 510 of the severe acute respiratory syndrome coronavirus spike protein are required for interaction with receptor. J. Virol. 2004;78:4552–4560. - PMC - PubMed

[6] Babcock G.J., Esshaki D.J., Thomas W.D., Ambrosino D.M. Amino acids 270 to 510 of the severe acute respiratory syndrome coronavirus spike protein are required for interaction with receptor. J. Virol. 2004;78:4552–4560. - PMC - PubMed

[7] Bahrami A., Vafapour M., Moazzami B., Rezaei N. Hyperinflammatory shock related to COVID-19 in a patient presenting with multisystem inflammatory syndrome in children: first case from Iran. J. Paediatr. Child Health. 2020 - PMC - PubMed

[8] Bahrami A., Vafapour M., Moazzami B., Rezaei N. Hyperinflammatory shock related to COVID-19 in a patient presenting with multisystem inflammatory syndrome in children: first case from Iran. J. Paediatr. Child Health. 2020 - PMC - PubMed

[9] Basiri A., Pazhouhnia Z., Beheshtizadeh N., Hoseinpour M., Saghazadeh A., Rezaei N. Regenerative medicine in COVID-19 treatment: real opportunities and range of promises. Stem cell reviews and reports. 2020:1–13. - PMC - PubMed

[10] Basiri A., Pazhouhnia Z., Beheshtizadeh N., Hoseinpour M., Saghazadeh A., Rezaei N. Regenerative medicine in COVID-19 treatment: real opportunities and range of promises. Stem cell reviews and reports. 2020:1–13. - PMC - PubMed

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Angiotensin-converting enzyme 2 (ACE2) receptor and SARS-CoV-2: Potential therapeutic targeting

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Angiotensin-converting enzyme 2 (ACE2) receptor and SARS-CoV-2: Potential therapeutic targeting

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