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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Pasteur Institute of Iran
2021-09-01
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| Series: | Journal of Medical Microbiology and Infectious Diseases |
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| Online Access: | https://jommid.pasteur.ac.ir/article-1-345-en.html |
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| author | Fatemeh Sefid Zahra Payandeh Bahman Khalesi Behzad Mansoori Marzieh Fotovvat Maryam Touhidinia |
| author_facet | Fatemeh Sefid Zahra Payandeh Bahman Khalesi Behzad Mansoori Marzieh Fotovvat Maryam Touhidinia |
| author_sort | Fatemeh Sefid |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-99c6e8b79ef043feab1c817ee0469a8a |
| institution | Kabale University |
| issn | 2345-5349 2345-5330 |
| language | English |
| publishDate | 2021-09-01 |
| publisher | Pasteur Institute of Iran |
| record_format | Article |
| series | Journal of Medical Microbiology and Infectious Diseases |
| spelling | doaj-art-99c6e8b79ef043feab1c817ee0469a8a2025-08-20T03:52:24ZengPasteur Institute of IranJournal of Medical Microbiology and Infectious Diseases2345-53492345-53302021-09-019315616910.52547/JoMMID.9.3.156Enhancement of SARS-CoV-2 Receptor Binding Domain -CR3022 Human Antibody Binding Affinity via In silico Engineering ApproachFatemeh Sefid0https://orcid.org/0000-0001-7055-8737Zahra Payandeh1https://orcid.org/0000-0003-2565-8231Bahman Khalesi2https://orcid.org/0000-0001-5723-8624Behzad Mansoori3https://orcid.org/0000-0001-9444-7134Marzieh Fotovvat4https://orcid.org/0000-0003-3081-4868Maryam Touhidinia5https://orcid.org/0000-0003-2267-3970Department of Medical Genetics, Shahid Sadoughi University of Medical Science, Yazd, Iran; Department of Biology, Science and Arts University, Yazd, IranImmunology Research Center, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Research and Production of Poultry Viral Vaccine, Razi Vaccine and Serum Research Institute, Agricultural Research Education and Extension Organization, Karaj, IranDepartment of Medical Genetics, Shahid Sadoughi University of Medical Science, Yazd, IranDepartment of Plant Science, Faculty of Biological Sciences, Kharazmi University, Tehran, IranDepartment of Biology, Faculty of Science, Yazd University, Yazd, IranIntroduction: 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.https://jommid.pasteur.ac.ir/article-1-345-en.htmlcoronavirussarscov- 2antibodybioinformaticsaffinity maturation |
| spellingShingle | Fatemeh Sefid Zahra Payandeh Bahman Khalesi Behzad Mansoori Marzieh Fotovvat Maryam Touhidinia Enhancement of SARS-CoV-2 Receptor Binding Domain -CR3022 Human Antibody Binding Affinity via In silico Engineering Approach Journal of Medical Microbiology and Infectious Diseases coronavirus sarscov- 2 antibody bioinformatics affinity maturation |
| title | Enhancement of SARS-CoV-2 Receptor Binding Domain -CR3022 Human Antibody Binding Affinity via In silico Engineering Approach |
| title_full | Enhancement of SARS-CoV-2 Receptor Binding Domain -CR3022 Human Antibody Binding Affinity via In silico Engineering Approach |
| title_fullStr | Enhancement of SARS-CoV-2 Receptor Binding Domain -CR3022 Human Antibody Binding Affinity via In silico Engineering Approach |
| title_full_unstemmed | Enhancement of SARS-CoV-2 Receptor Binding Domain -CR3022 Human Antibody Binding Affinity via In silico Engineering Approach |
| title_short | Enhancement of SARS-CoV-2 Receptor Binding Domain -CR3022 Human Antibody Binding Affinity via In silico Engineering Approach |
| title_sort | enhancement of sars cov 2 receptor binding domain cr3022 human antibody binding affinity via in silico engineering approach |
| topic | coronavirus sarscov- 2 antibody bioinformatics affinity maturation |
| url | https://jommid.pasteur.ac.ir/article-1-345-en.html |
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