Perspective: the nose and the stomach play a critical role in the NZACE2-Pātari* (modified ACE2) drug treatment project of SARS-CoV-2 infection

ABSTRACT

Background: COVID-19 has caused calamitous health, economic and societal consequences globally. Currently, there is no effective treatment for the infection. Areas covered: We have recently described the NZACE2-Pātari project, which seeks to administer modified Angiotensin Converting Enzyme 2 (ACE2) molecules early in the infection to intercept and block SARS-CoV-2 binding to the pulmonary epithelium. Expert opinion: Since the nasopharyngeal mucosa is infected in the first asymptomatic phase of the infection, treatment of the nose is likely to be safe and potentially effective. The intercepted virus will be swallowed and destroyed in the stomach. There is however a limited window of opportunity to alter the trajectory of the infection in an individual patient, which requires access to rapid testing for SARS-CoV-2. The proposed strategy is analogous to passive immunization of viral infections such as measles and may be of particular benefit to immunodeficient and unvaccinated individuals.

KEYWORDS:

• COVID-19
• nasal therapy
• nzace2-pātari
• sars-cov-2

Article highlights

• There is currently no effective treatment for COVID-19

• Safe and effective vaccines face financial and logistical challenges, which will hinder global deployment

• The virus initially infects the nasopharyngeal mucosa by binding cell-surface ACE2. By evading the innate immune system the virus is able to multiply exponentially and in some cases infect the lungs and other organs.

• Here we describe the potential use of recombinant modified ACE2 molecules to target the virus in the nasal phase

• Treating the virus in the asymptomatic incubation phase may alter the prognostic trajectory of the infection

• If deployed globally with rapid testing, this treatment may help mitigate the ongoing pandemic

• Rapid viral evolution may render some vaccines and monoclonal antibodies ineffective

• In contrast, modified ACE2 molecules are likely to be effective even with rapid viral evolution, as the virus requires ACE2 to gain entry into cells

Acknowledgments

The NZACE2-Pātari project has not reached clinical trials. Prototypes of these drugs have been produced and were partially tested in vitro. This project has been suspended because of a lack of funding and institutional support. We are gifting our ideas so colleagues with funding and facilities can bring these treatments to fruition to save lives. Science will ultimately prevail against SARS-CoV-2.

Author contributions

RA conceived the idea of intercepting the virus with ACE2 molecules and wrote the first draft of the manuscript. All other authors were part of the writing team and modified and edited the manuscript.

Declaration of interest

The project team may patent future modified ACE2 molecules to facilitate global use. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded