Assessment of neutralization susceptibility of Omicron subvariants XBB.1.5 and BQ.1.1 against broad-spectrum neutralizing antibodies through epitopes mapping
The emergence of new variants of the SARS-CoV-2 virus has posed a significant challenge in developing broadly neutralizing antibodies (nAbs) with guaranteed therapeutic potential. Some nAbs, such as Sotrovimab, have exhibited varying levels of efficacy against different variants, while others, such...
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| Format: | Article |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1236617/full |
| _version_ | 1797671965472849920 |
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| author | Masaud Shah Hyun Goo Woo Hyun Goo Woo |
| author_facet | Masaud Shah Hyun Goo Woo Hyun Goo Woo |
| author_sort | Masaud Shah |
| collection | DOAJ |
| description | The emergence of new variants of the SARS-CoV-2 virus has posed a significant challenge in developing broadly neutralizing antibodies (nAbs) with guaranteed therapeutic potential. Some nAbs, such as Sotrovimab, have exhibited varying levels of efficacy against different variants, while others, such as Bebtelovimab and Bamlanivimab-etesevimab are ineffective against specific variants, including BQ.1.1 and XBB. This highlights the urgent need for developing broadly active monoclonal antibodies (mAbs) providing prophylactic and therapeutic benefits to high-risk patients, especially in the face of the risk of reinfection from new variants. Here, we aimed to investigate the feasibility of redirecting existing mAbs against new variants of SARS-CoV-2, as well as to understand how BQ.1.1 and XBB.1.5 can evade broadly neutralizing mAbs. By mapping epitopes and escape sites, we discovered that the new variants evade multiple mAbs, including FDA-approved Bebtelovimab, which showed resilience against other Omicron variants. Our approach, which included simulations, endpoint free energy calculation, and shape complementarity analysis, revealed the possibility of identifying mAbs that are effective against both BQ.1.1 and XBB.1.5. We identified two broad-spectrum mAbs, R200-1F9 and R207-2F11, as potential candidates with increased binding affinity to XBB.1.5 and BQ.1.1 compared to the reference (Wu01) strain. Additionally, we propose that these mAbs do not interfere with Angiotensin Converting Enzyme 2 (ACE2) and bind to conserved epitopes on the receptor binding domain of Spike that are not-overlapping, potentially providing a solution to neutralize these new variants either independently or as part of a combination (cocktail) treatment. |
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| id | doaj.art-b352e6b151cc4f92801a39641994c5f9 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-03-11T21:23:12Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-b352e6b151cc4f92801a39641994c5f92023-09-28T05:28:21ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-09-011010.3389/fmolb.2023.12366171236617Assessment of neutralization susceptibility of Omicron subvariants XBB.1.5 and BQ.1.1 against broad-spectrum neutralizing antibodies through epitopes mappingMasaud Shah0Hyun Goo Woo1Hyun Goo Woo2Department of Physiology, Ajou University School of Medicine, Suwon, Republic of KoreaDepartment of Physiology, Ajou University School of Medicine, Suwon, Republic of KoreaDepartment of Biomedical Science, Graduate School, Ajou University, Suwon, Republic of KoreaThe emergence of new variants of the SARS-CoV-2 virus has posed a significant challenge in developing broadly neutralizing antibodies (nAbs) with guaranteed therapeutic potential. Some nAbs, such as Sotrovimab, have exhibited varying levels of efficacy against different variants, while others, such as Bebtelovimab and Bamlanivimab-etesevimab are ineffective against specific variants, including BQ.1.1 and XBB. This highlights the urgent need for developing broadly active monoclonal antibodies (mAbs) providing prophylactic and therapeutic benefits to high-risk patients, especially in the face of the risk of reinfection from new variants. Here, we aimed to investigate the feasibility of redirecting existing mAbs against new variants of SARS-CoV-2, as well as to understand how BQ.1.1 and XBB.1.5 can evade broadly neutralizing mAbs. By mapping epitopes and escape sites, we discovered that the new variants evade multiple mAbs, including FDA-approved Bebtelovimab, which showed resilience against other Omicron variants. Our approach, which included simulations, endpoint free energy calculation, and shape complementarity analysis, revealed the possibility of identifying mAbs that are effective against both BQ.1.1 and XBB.1.5. We identified two broad-spectrum mAbs, R200-1F9 and R207-2F11, as potential candidates with increased binding affinity to XBB.1.5 and BQ.1.1 compared to the reference (Wu01) strain. Additionally, we propose that these mAbs do not interfere with Angiotensin Converting Enzyme 2 (ACE2) and bind to conserved epitopes on the receptor binding domain of Spike that are not-overlapping, potentially providing a solution to neutralize these new variants either independently or as part of a combination (cocktail) treatment.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1236617/fullSARS-CoV-2neutralizationbroad-spectrumOmicronBQ.1.1XBB.1.5 |
| spellingShingle | Masaud Shah Hyun Goo Woo Hyun Goo Woo Assessment of neutralization susceptibility of Omicron subvariants XBB.1.5 and BQ.1.1 against broad-spectrum neutralizing antibodies through epitopes mapping Frontiers in Molecular Biosciences SARS-CoV-2 neutralization broad-spectrum Omicron BQ.1.1 XBB.1.5 |
| title | Assessment of neutralization susceptibility of Omicron subvariants XBB.1.5 and BQ.1.1 against broad-spectrum neutralizing antibodies through epitopes mapping |
| title_full | Assessment of neutralization susceptibility of Omicron subvariants XBB.1.5 and BQ.1.1 against broad-spectrum neutralizing antibodies through epitopes mapping |
| title_fullStr | Assessment of neutralization susceptibility of Omicron subvariants XBB.1.5 and BQ.1.1 against broad-spectrum neutralizing antibodies through epitopes mapping |
| title_full_unstemmed | Assessment of neutralization susceptibility of Omicron subvariants XBB.1.5 and BQ.1.1 against broad-spectrum neutralizing antibodies through epitopes mapping |
| title_short | Assessment of neutralization susceptibility of Omicron subvariants XBB.1.5 and BQ.1.1 against broad-spectrum neutralizing antibodies through epitopes mapping |
| title_sort | assessment of neutralization susceptibility of omicron subvariants xbb 1 5 and bq 1 1 against broad spectrum neutralizing antibodies through epitopes mapping |
| topic | SARS-CoV-2 neutralization broad-spectrum Omicron BQ.1.1 XBB.1.5 |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1236617/full |
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