Introduction: The COVID-19 pandemic has caused many deaths around the world. The appearance of new variants has complicated the eradication of SARS-CoV-2 despite all efforts to control the pandemic. CD147, also known as basigin or EMMPRIN, is a transmembrane glycoprotein that plays a crucial role in many different cancers and is required for entering the SARS-COV2 virus into the host cell. This study aimed to design novel inhibitory peptides against SARS-CoV-2 entry by disturbing CD147 /RBD interaction.
Methods: The three-dimensional structure of CD147 was extracted from the RCSB protein data bank and docked against the RBD. The important residues that participate in the formation of the SARS-CoV-2-CD147 interface were identified. The residues with unfavorable binding energies were chosen as mutation sites. Peptide inhibitors were developed by the mutation of RBD residues in the virus-receptors complex which had unfavorable energies. The final hits were selected from the initial library of peptides by evaluating their affinity for CD147 binding, safety, and allergenicity.
Results: A collection of 48 peptide candidates was created and the binding affinity of each peptide to the CD147 receptor was assessed through molecular docking. Finally, three non-allergenic and toxic inhibitory peptides with the lowest binding score were introduced.
Conclusion: Our results suggest that the designed inhibitory peptides could be promising therapeutic options for preventing COVID-19 infection and targeting various tumor types.