Combination Therapy Using Inhalable GapmeR and Recombinant ACE2 for COVID-19

Navin Kumar Verma; Mobashar Hussain Urf Turabe Fazil; Shane P Duggan; Dermot Kelleher

doi:10.3389/fmolb.2020.00197

Combination Therapy Using Inhalable GapmeR and Recombinant ACE2 for COVID-19

Front Mol Biosci. 2020 Aug 7:7:197. doi: 10.3389/fmolb.2020.00197. eCollection 2020.

Authors

Navin Kumar Verma^{1

2}, Mobashar Hussain Urf Turabe Fazil¹, Shane P Duggan², Dermot Kelleher^{1

2}

Affiliations

¹ Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
² Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.

Abstract

Here we report our perspective on applying GapmeR technology in combination with recombinant angiotensin-converting enzyme 2 (ACE2) in the treatment of COVID-19 patients. GapmeR is a cell-permeating antisense single-stranded DNA molecule that can be designed to specifically target intracellular severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Once internalized into host cells, such as lung alveolar cells, GapmeR molecules can bind to the viral RNA. This RNA/DNA hybrid will then be degraded by the RNase H enzyme abundantly present in the host cells. GapmeRs can be delivered to COVID-19 patients through inhalation or via nebulization. SARS-CoV-2-targeted GapmeR can also be given to frontline healthcare workers as a prophylactic protection. The recombinant ACE2 protein, the efficacy of which is being evaluated in clinical trials, will bind to the spike (S) glycoprotein of extracellular SARS-CoV-2 and potentially block viral infectivity. We propose that combining inhalable SARS-CoV-2-targeted GapmeRs with recombinant ACE2 could provide a viable and rapidly implementable more effective therapeutic approach for eradicating SARS-CoV-2 and save millions of lives.

Keywords: COVID-19 (2019-nCoV); GapmeR; angiotensin-converting enzyme 2; nasal delivery; therapy.