Modelling, Synthesis and Mass Spectrometry Characterization of Fusion Peptides to Inhibit the Spike Protein of SARS-CoV-2
Disciplines
Biochemistry | Medicinal-Pharmaceutical Chemistry
Abstract (300 words maximum)
The recent epidemic caused by COVID-19 left behind a devastating trail of destruction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused millions of deaths and is still active today. While some drugs have been approved for COVID treatment, peptide therapeutics proves to be a better, alternate solution. Peptides can act as inhibitors between the interaction of the S protein and the human angiotensin-converting enzyme 2. Based on previous research, certain peptides have a high affinity for attachment to the SARS-CoV-1. In this study, we performed molecular docking, synthesis, and characterization of a small Fp4 (19 amino acids) and large Fp13 (34 amino acids) peptides to see if they similarly inhibit the spike protein of SARS-CoV-2.
Fp4 is a beta-pleated sheet structure and a binding affinity score of -24.59 kcal/mol when docked against the heptad repeat 1 (HR1) domain in SARS-CoV-2. Fp13 is an alpha helix structure, with a binding affinity score of -252.18 when docked against HR1 showing a greater affinity to HR1 compared to Fp4. A solid phase peptide synthesis approach was utilized to synthesize the peptide on the rink amide resin. After synthesizing the peptides, the peptides were cleaved using 95% trifluoracetic acid to separate the peptides from the resin. The theoretical masses of Fp4 peptide were 1128.28 Da corresponds to [M+2H]+2 and 752.04 Da corresponds to [M+3]+3 which accurately matched with the experimental mass spectrometry data. For Fp13, the mass spectrometry results showed four peaks at 1836.42 Da, 1224.67 Da, and 918.34 Da correspond to 2+, 3+, and 4+ charge states and agreed with the theoretical masses. The synthesized peptides are now ready for an antiviral test. This test will determine the potency of the peptides and indicate if they can be used as a peptide therapeutic against SARS-CoV-2.
Academic department under which the project should be listed
CSM - Chemistry and Biochemistry
Primary Investigator (PI) Name
Mohammad A. Halim
Modelling, Synthesis and Mass Spectrometry Characterization of Fusion Peptides to Inhibit the Spike Protein of SARS-CoV-2
The recent epidemic caused by COVID-19 left behind a devastating trail of destruction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused millions of deaths and is still active today. While some drugs have been approved for COVID treatment, peptide therapeutics proves to be a better, alternate solution. Peptides can act as inhibitors between the interaction of the S protein and the human angiotensin-converting enzyme 2. Based on previous research, certain peptides have a high affinity for attachment to the SARS-CoV-1. In this study, we performed molecular docking, synthesis, and characterization of a small Fp4 (19 amino acids) and large Fp13 (34 amino acids) peptides to see if they similarly inhibit the spike protein of SARS-CoV-2.
Fp4 is a beta-pleated sheet structure and a binding affinity score of -24.59 kcal/mol when docked against the heptad repeat 1 (HR1) domain in SARS-CoV-2. Fp13 is an alpha helix structure, with a binding affinity score of -252.18 when docked against HR1 showing a greater affinity to HR1 compared to Fp4. A solid phase peptide synthesis approach was utilized to synthesize the peptide on the rink amide resin. After synthesizing the peptides, the peptides were cleaved using 95% trifluoracetic acid to separate the peptides from the resin. The theoretical masses of Fp4 peptide were 1128.28 Da corresponds to [M+2H]+2 and 752.04 Da corresponds to [M+3]+3 which accurately matched with the experimental mass spectrometry data. For Fp13, the mass spectrometry results showed four peaks at 1836.42 Da, 1224.67 Da, and 918.34 Da correspond to 2+, 3+, and 4+ charge states and agreed with the theoretical masses. The synthesized peptides are now ready for an antiviral test. This test will determine the potency of the peptides and indicate if they can be used as a peptide therapeutic against SARS-CoV-2.