Enhancement of SARS-CoV-2 Receptor Binding Domain -CR3022 Human Antibody Binding Affinity via In silico Engineering Approach
Introduction: The angiotensin-converting enzyme 2 (ACE2) is the effective primary receptor for SARS-CoV-2. The interaction between ACE2 and the spike protein of the virus is the crucial step for virus entry into the target cells. ACE2 receptor can be blocked by neutralizing antibodies (nAbs) such...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Pasteur Institute of Iran
2021-09-01
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| Series: | Journal of Medical Microbiology and Infectious Diseases |
| Subjects: | |
| Online Access: | https://jommid.pasteur.ac.ir/article-1-345-en.html |
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| Summary: | Introduction: The angiotensin-converting enzyme 2 (ACE2) is the effective
primary receptor for SARS-CoV-2. The interaction between ACE2 and the
spike protein of the virus is the crucial step for virus entry into the target cells.
ACE2 receptor can be blocked by neutralizing antibodies (nAbs) such as
CR3022 which targets the virus receptor-binding site. Enhancing the binding
affinity between CR3022 and ACE2 would lead to a more efficient blockade of
virus entry. Methods: In this regard, the amino acids with central roles in the
binding affinity of CR3022 antibody to spike protein were substituted. The best
mutations to increase the affinity of antibodies were also selected based on
protein-protein docking and molecular dynamics simulations. Result: The
variants 45 (H:30I/G, H:55D/F, H: 103S/Y, L:59T/F, L:98Y/A), 60(H:31T/D,
H:55D/E, H:103S/Y, L:59T/D, L:98Y/F), 67(H:30I/G, H:55D/F, H:103S/Y,
L:56 W/L, L:59T/Y, L:61E/G), 69(H:31T/D, H:55D/F, H:103S/Y, L:59T/F,
L:98Y/A), and 71(H: 31T/D, H:55D/F, H:103S/Y) with respective binding
affinities of -167.3, -167.5, -161.6, -173.0, and -169.8 Kcal/mol had higher
binding affinities against the RBD of the SARS-CoV2 spike protein compared
to the wild-type Ab. Conclusion: The engineered antibodies with higher binding
affinities against the target protein can improve specificity and sensitivity. Thus,
a more successful blockade of the ACE2 is achieved, resulting in a better
therapeutic outcome. In silico studies can pave the way for designing these
engineered molecules avoiding the economic and ethical challenges. |
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| ISSN: | 2345-5349 2345-5330 |