Texas Southern University Houston, Texas, United States
Purpose: The ongoing pandemic of coronavirus disease (COVID-19) caused by the highly infectious pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represents a global public health challenge. The emergence of deadly SARS-CoV-2 variants with mutations on the viral genes has made it more imperative to discover therapeutics that target the host receptors for COVID-19 treatment. Therefore, our research has targeted the critical host entry receptor for SARS-CoV-2 entry into the human cells, Angiotensin-converting enzyme-2 (ACE2). SARS-CoV-2 is an enveloped RNA beta coronavirus that infects human cells via interaction with the ACE2 receptor, through a receptor binding domain of the spike protein followed by viral replication and virus dissemination. ACE2 is an essential component of the renin-angiotensin system that converts Angiotensin II (Ang II) to Angiotensin 1-7, a potent vasopressor. Although ACE2 facilitates viral entry, it provides defense against acute lung injury, therefore the ACE2/Ang 1-7 pathway must be carefully manipulated without disrupting the balance of the renin angiotensin system. Methods: Using a COVID-19 Spike-ACE2 Binding Assay, we evaluated the effects of OJT009 on disrupting the interaction between recombinant human ACE2 (rhACE2) and the RBD of the S protein of SARS-CoV-2. Results: Herein, we discovered that OJT009 is an effective modulator of the interaction between the RBD of SARS-CoV-2 spike protein and human rhACE2. Conclusion: Based on our findings, OJT009 represents a promising drug class that could be further evaluated as a lead series in developing chemotherapeutics for COVID-19 treatment.
