Rational design of an anti-cancer peptide inhibiting CD147 / Cyp A interaction

The CD147 / Cyp A interaction is a critical pathway in cancer types and an essential factor in entering the COVID-19 virus into the host cell. Melittin acts as an inhibitory peptide in cancer types by blocking the CD147/ Cyp A interaction. The clinical application of Melittin is limited due to weak penetration into can-cer cells. TAT is an arginine-rich peptide with high penetration ability into cells widely used in drug deliv-ery systems. This study aimed to design a hybrid peptide derived from Melittin and TAT to inhibit CD147 /Cyp A interaction. An amino acid region with high anti-cancer activity in Melittin was selected based on the physicochemical properties. Based on the results, a truncated Melittin peptide with 15 amino acids by the GGGS linker was fused to a TAT peptide (nine amino acids) to increase the penetration rate into the cell. A new hybrid peptide analog(TM) was selected by replacing the glycine with serine based on random point mutation. Docking results indicated that the TM peptide acts as an inhibitory peptide with high binding energy when interacting with CD147 and the CypA proteins. RMSD and RMSF results con-firmed the high stability of the TM peptide in interaction with CD147. Also, the coarse-grained simulation showed the penetration potential of TM peptide into the DOPS-DOPC model membrane. Our findings in-dicated that the designed multifunctional peptide could be an attractive therapeutic candidate to halter tumor types and COVID-19 infection. (c) 2022 Elsevier B.V. All rights reserved.

Automated summary

The interaction between CD147/Cyp A is a critical pathway for certain cancer types and the entry of COVID-19 virus into host cells. A hybrid peptide derived from Melittin and TAT was designed to inhibit the CD147/Cyp A interaction. The hybrid peptide showed potential as a therapeutic candidate for tumor types and COVID-19 infection.