Design and Synthesis of Indolicidin and Temporin Peptide Analogues to inhibit the Main Protease of SARS-CoV-2
Disciplines
Analytical Chemistry | Computational Chemistry | Medicinal-Pharmaceutical Chemistry
Abstract (300 words maximum)
The development of therapies to treat SARS-Cov2 is paramount to combat the continued persistence of the infection that has claimed the lives of 6 million people worldwide and continues to impact communities around the world today. Current vaccines have been found to lack longevity requiring numerous booster shots following the initial vaccination. The main protease (Mpro) of SARS-Cov-2, is responsible for converting viral proteins pp1a and pp1b into non-structural proteins used to construct the replisome and was found to be a suitable target for peptides. Compared to small molecules, peptide therapeutics are thus gaining increasing popularity as they are easy to synthesis, highly selective and have fewer side effects. In this study, various analogues were designed computationally from Indolicidin and Temporin L Peptides. 3D model of the peptides was generated by PEP-FOLD3. Molecular docking was performed between the peptides and main protease of SARS-CoV-2. The selected analogues were synthesized using solid phase peptide synthesis protocol on the rink amide resin. After synthesis, the peptides are deprotected and cleaved from the resin using a high TFA cleavage cocktail. Next, the peptides are dissolved in 10% acetic acid and recovered by lyophilization under high vacuum. The purity of each peptide is evaluated by LC-MS using Agilent 1290 Infinity coupled with Thermo LTQ XL mass spectrometer. The experimental mass-to-charge ration of these peptides are agreed with the theoretical m/z. To assess the inhibition efficiency of the synthesized peptides, protease inhibitor assay will be conducted.
Academic department under which the project should be listed
CSM - Chemistry and Biochemistry
Primary Investigator (PI) Name
Mohammad A. Halim
Design and Synthesis of Indolicidin and Temporin Peptide Analogues to inhibit the Main Protease of SARS-CoV-2
The development of therapies to treat SARS-Cov2 is paramount to combat the continued persistence of the infection that has claimed the lives of 6 million people worldwide and continues to impact communities around the world today. Current vaccines have been found to lack longevity requiring numerous booster shots following the initial vaccination. The main protease (Mpro) of SARS-Cov-2, is responsible for converting viral proteins pp1a and pp1b into non-structural proteins used to construct the replisome and was found to be a suitable target for peptides. Compared to small molecules, peptide therapeutics are thus gaining increasing popularity as they are easy to synthesis, highly selective and have fewer side effects. In this study, various analogues were designed computationally from Indolicidin and Temporin L Peptides. 3D model of the peptides was generated by PEP-FOLD3. Molecular docking was performed between the peptides and main protease of SARS-CoV-2. The selected analogues were synthesized using solid phase peptide synthesis protocol on the rink amide resin. After synthesis, the peptides are deprotected and cleaved from the resin using a high TFA cleavage cocktail. Next, the peptides are dissolved in 10% acetic acid and recovered by lyophilization under high vacuum. The purity of each peptide is evaluated by LC-MS using Agilent 1290 Infinity coupled with Thermo LTQ XL mass spectrometer. The experimental mass-to-charge ration of these peptides are agreed with the theoretical m/z. To assess the inhibition efficiency of the synthesized peptides, protease inhibitor assay will be conducted.