Finding Molecular Inhibitors to Neutralize SARS-CoV-2 Infection and its Variants

The COVID-19 outbreak has affected global public health and resulted in 487 million confirmed cases. The SARS-CoV-2 spike protein binds to the human ACE2 receptor through its receptor binding domain which mediates viral entry and membrane fusion. The virus invades the body through the respiratory and circulatory systems of people of all ages. The pandemic has underscored a need to identify effective molecular inhibitors of the viral spike protein. We found a small molecule, CD04872SC, through Maybridge and ZINC library analysis and were able to show that it can neutralize SARS-CoV-2 infection, along with its Delta and Omicron variants. This inhibitor forms close associations with the hydrophobic residues of the spike protein's receptor binding domain in order to block binding with the ACE2 receptor. We also conducted a thermal shift assay in order to demonstrate the binding affinity between the known inhibitor and each viral protein. The data from our fluorescence and computational analyses indicates that the molecular inhibitor stabilizes each variant and has the potential to be broad-spectrum viral treatment.