Author(s): Amjad Ayoub, Nishat Fatima, Vichitra Kaushik


DOI: 10.52711/0974-360X.2021.00597   

Address: Amjad Ayoub*, Nishat Fatima, Vichitra Kaushik
Faculty of Pharmacy, Al-Hawash Private University, Homs, Syria – 22743.
*Corresponding Author

Published In:   Volume - 14,      Issue - 6,     Year - 2021

The COVID-19 infection and associated severe respiratory distress and mortality have raised public health concerns worldwide. The membrane bound angiotensin-converting enzyme 2 (ACE2) is present on various tissues, including the pulmonary epithelium, and is the cellular receptor for the binding of SARS-CoV2. Rapid designing, production, and testing of soluble ACE2-like peptide are highly recommended. We conducted an extensive literature review of COVID-19 and soluble recombinant human (rhACE2). Several reports have indicated the beneficial effect of recombinant human ACE2. In the present work, we explore the blocking action of soluble ACE2 against the spike S protein of SARS-CoV-2 virion in the lungs. We propose localized delivery of soluble ACE2 to the lungs, via aerosolized formulation or nasal drops, due to the limitations of parenteral administration of available bioactive proteins. Based on available literature, we suggest novel aerosolized pulmonary delivery or nasal drops containing soluble recombinant human ACE2- like peptide for therapy or as a prophylactic measure against COVID-19.

Cite this article:
Amjad Ayoub, Nishat Fatima, Vichitra Kaushik. Pulmonary Aerosolized Formulation or Nasal Drops containing Recombinant Human Angiotensin converting Enzyme 2 (rhACE2) as a Potential Therapy against COVID-19. Research Journal of Pharmacy and Technology. 2021; 14(6):3433-6. doi: 10.52711/0974-360X.2021.00597

Amjad Ayoub, Nishat Fatima, Vichitra Kaushik. Pulmonary Aerosolized Formulation or Nasal Drops containing Recombinant Human Angiotensin converting Enzyme 2 (rhACE2) as a Potential Therapy against COVID-19. Research Journal of Pharmacy and Technology. 2021; 14(6):3433-6. doi: 10.52711/0974-360X.2021.00597   Available on:

1.    Ahmed SF, Quadeer AA and MacKey MR. Preliminary identification of potential Vaccine targets for Covid-19 Corona virus (SARS-CoV-2) based on SARS-CoV immunological studies. Viruses. 2020; 254: 1-15.
2.    Sindhu TJ, Arathi K N, Akhilesh K J, Anju J, Binsiya K P, Blessy T, Elizabeth W. Antiviral screening of Clerodol derivatives as COV 2 main protease inhibitor in Novel Corona Virus Disease: In silico approaches. Asian J. Pharm. Tech. 2020; 10(2): 60-64.
3.    Gelas FA, Drueke TB. Blockade of SARS-CoV-2 infection by soluble ACE2. Kidney International. 2020; 1-3.
4.    Zhou P et al . Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin. bioRxiv (2020) preprint.
5.    Li W et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003; 426(6965): 450–454.  
6.    Serfozo P et al. Ang II (angiotensin II) conversion to angiotensin-(1-7) in the circulation is pop (prolyloligopeptidase) -dependent and Ace2 (angiotensin-converting enzyme 2)- independent. Hypertension. 2020; 75: 173–182.
7.    Hamming I 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.  
8.    Hofmann H et al. Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry. Proc Natl Acad Sci. 2005; 102: 7988–93.  
9.    Batlle D, Wysockil J and Satchell K. Soluble angiotensin-converting enzyme 2: a potential approach for coronavirus infection therapy? Clin Sci.  2020; 134 (5): 543–545.
10.    Zhou P  et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature (2020) 579: 270–3.
11.    Li F. “Structure, Function, and Evolution of Coronavirus Spike Proteins” Annu. Rev Virol. 2016; 3:237.
12.    Wan Y et al. “Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus”. J Virol. 2020; 94(7): pii: e00127-20.
13.    Li F. Receptor recognition mechanisms of coronaviruses: a decade of structural studies. J Virology. 2015; 89 (4): 1954–1964.
14.    Information scientist Posted on April 16 2020 (Accessed on 13/05/2019)
15.    Sonia M, Dr. Prem S, Subhash K W, Tarunika B.  Worldwide spread of COVID-19 Pandemic and risk factors among Co-morbid conditions especially Diabetes Mellitus in India. Research J. Pharm. and Tech 2020; 13(5): 2530-2532.
16.    Minato T et al.  “B38-CAP is a bacteria-derived ACE2-like enzyme that suppresses hypertension and cardiac dysfunction” Nature Communications. 2020; 11(1): 1-12.
17.    Li Y et al. “Angiotensin-converting enzyme 2 prevents lipopolysaccharide -induced rat acute lung injury via suppressing the ERK1/2 and NF-κB signaling pathways”. Scientific Reports. 2016; 6:27911 1-14.
18.    Kuba K et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury. Nat Med. 2005; 11: 875–79.
19.    Kuba K, Imai Y and Penninger JM. “Angiotensin-converting enzyme 2 in lung diseases”. Current Opinion in Pharmacology. 2006; 6(3): 271–6.
20.    Duana K et al. Effectiveness of convalescent plasma therapy in severeCOVID-19 patients. PNAS Latest Articles, 1 of 7. doi:10.1073/pnas.2004168117/-/DC Supplemental.
21.     Thompson R. Pandemic potential of 2019-nCoV. Lancet Infect Disease. 2020; 20(3): 280.
22.    Ong SWX et al. Air, Surface Environmental, and Personal Protective Equipment Contamination by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) from a Symptomatic Patient. JAMA. 2020; 323 (16):1610-12.
23.    Schoeman D and Burtram C. Fielding. “Coronavirus envelope protein: current knowledge”. Virology Journal. 2019; 16 (1): 69.
24.    Lei C et al. Potent neutralization of 2019 novel coronavirus by recombinant ace2-ig. bioRxiv (2020)
25.    Imai Y et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005; 436(7047): 112–116.
26.    Zhang R et al. Mechanical stress and the induction of lung fibrosis via the midkine signaling pathway. Am J Respir Crit Care Med. 2015; 192: 315–23.
27.    Asperen WVRM et al. Acute respiratory distress. syndrome leads to reduced ratio of ACE/ACE2 activities and is prevented by angiotensin- (1-7) or an angiotensin II receptor antagonist. J Pathol. 2011; 225 (4): 618–27.
28.    Namdev N, Upadhyay S. Challenges and approaches for Oral protein and peptide drug delivery. Research J. Pharm. and Tech. 2016; 9(3): 305-312.
29.     Sunitha MR, Mallikarjun SR, Mahesh AC, Santhosh BS, Surekha CH, Naveen K. Novel Approaches for Delivery of Proteins and
Peptides – A Review. Research J. Pharma. Dosage Forms and Tech. 2013; 5(1): 7-11.
30.    Bajracharya R et al. Recent Advancements in Non-Invasive Formulations for Protein Drug Delivery. Computational and Structural Biotechnology. 2019; 17: 1290–1308.
31.    Neutral MR and Kozlowski PA. Mucosal Vaccines. The promise and the challenge. Nat Rev Immunol. 2006; 6: 148-58.
32.    Jitendra Sharma PK, Bansal S and Banik A. Non-invasive routes of proteins and peptides drug delivery. Indian J Pharm Sci. 2011; 73(4): 367–75.
33.    Ray A, Mandal A and Mitra AK. Recent patents in pulmonary delivery of macromolecules. Rec Pat Drug Deliv Formul. 2015; 9(3): 225–36.
34.    Gangurde H et al. Approaches and devices used in pulmonary drug delivery system: a review. Asian J Phar Res Health Care. 2014; 4 (1): 11–27.
35.    Kunda N et al. Nanocarriers targeting dendritic cells for pulmonary vaccine delivery. Pharm Res. 2013; 30 (2): 325–341.  
36.    Khale A. Composition and Characterization of Metered Dose Inhalers. Research J. Pharm. and Tech. 2011; 4(5): 704-709.
37.    Osmana N et al. Carriers for the targeted delivery of aerosolized macromolecules for pulmonary pathologies. Expert Opinion on Drug Delivery. 2018; 15 (8): 821–834.
38.    Sungnak W et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nature Medicine. 2020; 26 (5): 681-687.
39.    Lohar MS, Hiralal S. C, Chandrakant S.G, Dinesh KJ, Dheeraj T B. Nasal drug delivery an overview. Research J. Pharma. Dosage Forms and Tech. 2011; 3(5): 159-166.
40.    Prajakta N, Ankita P, Kore PS, Mohite SK. Advanced drug delivery-Inhalation of nanoparticles to treat coronary failure. Research J. Pharm. and Tech. 2018; 11(12): 5669-5671.
41.    Saudagar RB, Mita KM. Review on in-situ Nasal gel drug delivery system.  Research J. Pharm. and Tech.2017;10(6): 1870-1876.
42.    Patton JS, Fishburn CS and Weers JG. The lungs as a portal of entry for systemic drug delivery. Proc Am Thorac Soc.2004; 1: 338–44.
43.    Rajesh B, Nikhat SR, Nivethithai P, Areefullah SH. Approaches and Challenges of Protein and Peptide delivey. Research J. Pharm. and Tech.2010; 3(2): 379-384.
44.    Rishabh P, Singh AV, Awanish P, Poonam T, Majumdar SK, Nath LK.  Proteins and Peptide drugs: A brief Review. Research J. Pharm. and Tech. 2009; 2 (2): 228-233.

Recomonded Articles:

Research Journal of Pharmacy and Technology (RJPT) is an international, peer-reviewed, multidisciplinary journal.... Read more >>>

RNI: CHHENG00387/33/1/2008-TC                     
DOI: 10.5958/0974-360X 

56th percentile
Powered by  Scopus

SCImago Journal & Country Rank

Recent Articles


Not Available