The COVID-19 pandemic has underscored the urgent need to develop highly potent and safe medications that are complementary to the role of vaccines. Specifically, it has exhibited the need for orally bioavailable broad-spectrum antivirals that are able to be quickly deployed against newly emerging viral pathogens. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and its variants Delta and Omicron are still a major threat to patients of all ages. In this brief report, we describe that the small molecule CD04872SC was able to neutralize SARS-CoV2 infection with a half-maximal effective concentration (EC50) = 248 uM. Serendipitously, we also were able to observe that CD04872SC inhibited the infection of the SARS-CoV-2 variants; Delta (EC50 = 152 uM) and Omicron (EC50 = 308 uM). These properties may define CD04872SC as a potential broad-spectrum candidate lead for the development of treatments for COVID-19.
The molecular structure shows the interface of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (white surface) with the human ACE2 receptor (pink surface). CD04872SC is predicted to bind on the face leading to the potential disruption of the complex. Drug screening of the selected top compounds (each at a concentration of 100 uM) was evaluated for their antiviral activity against SARS-CoV-2, as defined by their percent infection inhibition.
