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.
Highlights
COVID-19 or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to threaten human health worldwide
In addition to specificity and highly efficient gene silencing, we have shown that GapmeRs can internalize into target cells by macropinocytosis or gymnosis (Fazil et al, 2016; Verma et al, 2017; Ong et al, 2018); requiring no additional delivery assistance or transfection agents
Monteil et al (2020) have shown the therapeutic potential of human recombinant soluble angiotensin-converting enzyme 2 (ACE2) protein to inhibit the replication of SARS-CoV-2
Summary
COVID-19 or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to threaten human health worldwide. The infection is established by virus particles following their entry through airway and binding of viral S protein to the receptor angiotensin-converting enzyme 2 (ACE2) expressed on type II alveolar cells of lung (Zou et al, 2020).
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