Potent neutralising monoclonal antibodies targeting the spike of NL63 coronavirus
Abstract NL63 is an alphacoronavirus that uses the same ACE2 receptor as SARS-CoV and SARS-CoV-2, but generally causes mild respiratory illness. In a cohort of healthy adults, we characterised humoral responses against NL63 spike and isolated a panel of human monoclonal antibodies (mAbs), including...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-04-01
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| Series: | npj Viruses |
| Online Access: | https://doi.org/10.1038/s44298-025-00116-x |
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| Summary: | Abstract NL63 is an alphacoronavirus that uses the same ACE2 receptor as SARS-CoV and SARS-CoV-2, but generally causes mild respiratory illness. In a cohort of healthy adults, we characterised humoral responses against NL63 spike and isolated a panel of human monoclonal antibodies (mAbs), including five with potent viral neutralising activity. Four neutralising mAbs blocked ACE2 receptor engagement and were found to target the receptor binding motif. A single mAb targeting the S2 subunit displayed potent neutralisation activity comparable to those directly blocking receptor engagement. The S2 mAb targets a membrane proximal heptad repeat 2 (HR2) region in spike that is absent in betacoronaviruses, potentially revealing a site of vulnerability unique to alphacoronaviruses. For all neutralising mAbs, putative epitopes were highly conserved in over 200 NL63 sequences, including recent clinical isolates. A deeper understanding of the recognition of alphacoronavirus spike by human antibodies will guide vaccine and therapeutic development against alphacoronavirus threats. |
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| ISSN: | 2948-1767 |