Peptides Therapeutics for Covid-19: Targeting the Protein-Protein Interactions of RBD-ACE2
Disciplines
Analytical Chemistry | Biochemistry | Bioinformatics | Medicinal-Pharmaceutical Chemistry | Other Immunology and Infectious Disease
Abstract (300 words maximum)
In 2020, SARS-CoV-2 affected millions of people. As of 12 March 2022, there have been more than 457 million cases worldwide, and over six million deaths have resulted from the pandemic. Pharmaceutical companies such as Pfizer-BioNTech, Moderna, and Janssen have developed the vaccines. Although vaccines have lowered the infection rate and helped somewhat with immunity, the emerging delta and omicron variants of the virus are still infecting millions and killing thousands of people every day. While various small molecules have demonstrated promising results targeting the viral proteases, such as the main proteases and papain-like proteases, few studies have investigated the use of antiviral peptides targeting the receptor binding domain (RBD) and angiotensin converting enzyme 2 (ACE2) complex. In this study, we reported the molecular docking and in-vitro studies to identify potent peptide inhibitors of the SARS-CoV-2 spike protein and ACE2 receptor interaction. Preliminary results showed that two peptides have high binding affinity and non-bonding interactions with RBD-ACE2 complex compared to the affinity and interactions of the peptides with RBD only. The highest binding affinity is noticed for AVP1795 peptide with a global energy of -65.38 kcal/mol. This peptide also showed greater attractive van der Waals interaction compared to other peptides. The interaction of this peptide with the RBD-ACE2 complex revealed that the peptide interacted more with the residues Glu325, Thr324, Asn322, Pro321 Met383, Ala384, and Arg384 of ACE2 than the residues Arg 408 and Val503 of RBD. The best peptides were synthesized with an acetylated N-terminus and amidated C-terminus on a Liberty Blue microwave peptide synthesizer (CEM). The purity of each peptide was evaluated by Agilent 1290 UPLC coupled with LTQ XL mass spectrometer. These results can accelerate the rational design of selective peptide inhibitors targeting the interface of the RBD and ACE2 complex.
Academic department under which the project should be listed
CSM - Chemistry and Biochemistry
Primary Investigator (PI) Name
Mohammad A. Halim
Peptides Therapeutics for Covid-19: Targeting the Protein-Protein Interactions of RBD-ACE2
In 2020, SARS-CoV-2 affected millions of people. As of 12 March 2022, there have been more than 457 million cases worldwide, and over six million deaths have resulted from the pandemic. Pharmaceutical companies such as Pfizer-BioNTech, Moderna, and Janssen have developed the vaccines. Although vaccines have lowered the infection rate and helped somewhat with immunity, the emerging delta and omicron variants of the virus are still infecting millions and killing thousands of people every day. While various small molecules have demonstrated promising results targeting the viral proteases, such as the main proteases and papain-like proteases, few studies have investigated the use of antiviral peptides targeting the receptor binding domain (RBD) and angiotensin converting enzyme 2 (ACE2) complex. In this study, we reported the molecular docking and in-vitro studies to identify potent peptide inhibitors of the SARS-CoV-2 spike protein and ACE2 receptor interaction. Preliminary results showed that two peptides have high binding affinity and non-bonding interactions with RBD-ACE2 complex compared to the affinity and interactions of the peptides with RBD only. The highest binding affinity is noticed for AVP1795 peptide with a global energy of -65.38 kcal/mol. This peptide also showed greater attractive van der Waals interaction compared to other peptides. The interaction of this peptide with the RBD-ACE2 complex revealed that the peptide interacted more with the residues Glu325, Thr324, Asn322, Pro321 Met383, Ala384, and Arg384 of ACE2 than the residues Arg 408 and Val503 of RBD. The best peptides were synthesized with an acetylated N-terminus and amidated C-terminus on a Liberty Blue microwave peptide synthesizer (CEM). The purity of each peptide was evaluated by Agilent 1290 UPLC coupled with LTQ XL mass spectrometer. These results can accelerate the rational design of selective peptide inhibitors targeting the interface of the RBD and ACE2 complex.