Very limited drug and diagnostic reagents are currently available to tackle the emergence of SARS-CoV-2. However, recent findings about the structure of the complex about PD of ACE2 and RBD of SARS-CoV-2 spike protein hold great promise for the design of novel vaccines and peptides. To provide some suggestions for the design of peptide-based drug or diagnostic reagents antagonizing SARS-CoV-2, and describe the interactions between the receptor-binding domain of SARS-CoV-2 and PD domain of its receptor, ACE2.
Based on the PD-RBD crystal structure, the molecular interaction details of PD-RBD was contrasted.
Amino acid mutations located in RBM of SARS-CoV result in the formation of new interactions between SARS-CoV-2 and α-helix 1, which can increase the binding affinity of SARS-CoV-2 to ACE2. It is confirmed that the α-helix 1 on ACE2 is the most important domain for binding spike glycoprotein of SARS-CoV-2, which can be used as a leading peptide for drug and diagnostic reagents development.
Based on the molecular-level characterization analysis between the PD and RBD, severe important amino acid residues (Q24, T27, K31, and H34) on α-helix 1 are proposed to mutate into increasing the binding affinity. Although the information provided in this study is predictive and based on no experimental evidence, it may provide useful suggestions for the experimental scientists to synthesize the proposed peptide and test their binding affinity and blocking capacity, and may be helpful for the understanding of SARS-CoV-2 entry.
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Posted 19 Aug, 2020
Posted 19 Aug, 2020
Very limited drug and diagnostic reagents are currently available to tackle the emergence of SARS-CoV-2. However, recent findings about the structure of the complex about PD of ACE2 and RBD of SARS-CoV-2 spike protein hold great promise for the design of novel vaccines and peptides. To provide some suggestions for the design of peptide-based drug or diagnostic reagents antagonizing SARS-CoV-2, and describe the interactions between the receptor-binding domain of SARS-CoV-2 and PD domain of its receptor, ACE2.
Based on the PD-RBD crystal structure, the molecular interaction details of PD-RBD was contrasted.
Amino acid mutations located in RBM of SARS-CoV result in the formation of new interactions between SARS-CoV-2 and α-helix 1, which can increase the binding affinity of SARS-CoV-2 to ACE2. It is confirmed that the α-helix 1 on ACE2 is the most important domain for binding spike glycoprotein of SARS-CoV-2, which can be used as a leading peptide for drug and diagnostic reagents development.
Based on the molecular-level characterization analysis between the PD and RBD, severe important amino acid residues (Q24, T27, K31, and H34) on α-helix 1 are proposed to mutate into increasing the binding affinity. Although the information provided in this study is predictive and based on no experimental evidence, it may provide useful suggestions for the experimental scientists to synthesize the proposed peptide and test their binding affinity and blocking capacity, and may be helpful for the understanding of SARS-CoV-2 entry.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
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