Project Title
Antiviral-Cell Penetrating Peptide Conjugate as Leads for Targeting the Main Protease of SARS-CoV-2
Academic department under which the project should be listed
CSM - Chemistry and Biochemistry
Research Mentor Name
Mohammad A. Halim
Abstract (300 words maximum)
Peptides play an important role in the immune defenses of the host against several distinct types of infections. Hence, peptides represent a promising therapeutic approach for the treatment of SARS-CoV-2 infections. Temporin L, known for its antimicrobial characteristics, has an alpha-helical structure that has been found to interact with the cytoplasmic membrane and induce the formation of pores. In-vitro assessment of the Temporin L1 inhibitor was found to exhibit moderate activity against Mpro of SARS-CoV-2. Notably, the conformational analysis suggests that the rigid structure of Temporin L (TL) facilitates favorable binding to Mpro's active site. Here, we introduce a new approach to the design, synthesis, and characterization of the conjugation of Temporin L to various cell-penetrating peptides (CPP) inhibitors targeting the main protease (Mpro) of SARS-CoV-2. This conjugation can be able to enhance 4- to 16-fold antiviral activity. Our theoretical study of the SARS-CoV-2 Mpro suggests that the TL-CPP inhibitor can bind the active site of Mpro in the predicted manner. The structural insights observed from Molecular Dynamics (MD) simulations provide a clearer understanding of how the conjugate TL-CPP peptide inhibitor could interact with Mpro's active site. Liquid chromatography coupled with mass spectrometry (LC-MS) was used to characterize the peptide intermediates, demonstrating that experimental m/z values corresponded with theoretical m/z values. Subsequently, the results of our study provide crucial insight into the therapeutic approach of developing peptide inhibitors against the main protease of SARS-CoV-2. Furthermore, the findings of this study provide a groundwork understanding of the in-vitro main protease assay validation to identify the lead conjugate TL-CPP peptides targeting SARS-CoV-2.
Antiviral-Cell Penetrating Peptide Conjugate as Leads for Targeting the Main Protease of SARS-CoV-2
Peptides play an important role in the immune defenses of the host against several distinct types of infections. Hence, peptides represent a promising therapeutic approach for the treatment of SARS-CoV-2 infections. Temporin L, known for its antimicrobial characteristics, has an alpha-helical structure that has been found to interact with the cytoplasmic membrane and induce the formation of pores. In-vitro assessment of the Temporin L1 inhibitor was found to exhibit moderate activity against Mpro of SARS-CoV-2. Notably, the conformational analysis suggests that the rigid structure of Temporin L (TL) facilitates favorable binding to Mpro's active site. Here, we introduce a new approach to the design, synthesis, and characterization of the conjugation of Temporin L to various cell-penetrating peptides (CPP) inhibitors targeting the main protease (Mpro) of SARS-CoV-2. This conjugation can be able to enhance 4- to 16-fold antiviral activity. Our theoretical study of the SARS-CoV-2 Mpro suggests that the TL-CPP inhibitor can bind the active site of Mpro in the predicted manner. The structural insights observed from Molecular Dynamics (MD) simulations provide a clearer understanding of how the conjugate TL-CPP peptide inhibitor could interact with Mpro's active site. Liquid chromatography coupled with mass spectrometry (LC-MS) was used to characterize the peptide intermediates, demonstrating that experimental m/z values corresponded with theoretical m/z values. Subsequently, the results of our study provide crucial insight into the therapeutic approach of developing peptide inhibitors against the main protease of SARS-CoV-2. Furthermore, the findings of this study provide a groundwork understanding of the in-vitro main protease assay validation to identify the lead conjugate TL-CPP peptides targeting SARS-CoV-2.