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Front Microbiol
. 2025 Jul 16:16:1593095.
doi: 10.3389/fmicb.2025.1593095. eCollection 2025. Cross-neutralization ability of anti-MERS-CoV monoclonal antibodies against a variety of merbecoviruses
Lin Pan # 1 , Yu Kaku # 1 , Jarel Elgin Tolentino 1 2 , Yusuke Kosugi 1 3 , Kei Sato 1 2 3 4 5 6 7
Affiliations
In the 21st century, three severe human coronavirus infections have occurred. One of them is the Middle East respiratory syndrome coronavirus (MERS-CoV), a merbecovirus belonging to the family Coronaviridae, is a human pathogenic coronavirus first detected in 2012. Several monoclonal antibodies (mAbs) have been developed for both therapeutics and prevention of MERS-CoV infection. However, the extent to which these anti-MERS-CoV antibodies neutralize other merbecoviruses remains unclear. Here, we evaluated the cross-neutralization ability of ten anti-MERS-CoV mAbs against the pseudoviruses with the spike proteins of five merbecoviruses known to bind to dipeptidyl peptidase 4 (DPP4): three clades of MERS-CoV, a bat-derived merbecovirus (BtCoV-422) and a pangolin-derived merbecovirus (MjHKU4r-CoV). We show that all eight mAbs targeting the receptor-binding domain (RBD) potently neutralize all MERS-CoV clades, but not BtCoV-422 and MjHKU4r-CoV. Of these, the neutralization potency of one mAb, m336, against the MERS-CoV clade B declined due to the V530L substitution detected in certain isolates during the 2015 outbreak in South Korea. On the other hand, although BtCoV-422 was neutralized by the two non-RBD mAbs, 7D10 (targeting the N-terminal domain) and G4 (targeting the S2 subunit), MjHKU4r-CoV found to be resistant. Our findings suggest that combining multiple mAbs targeting different epitopes could be a promising strategy for prevention of future outbreaks caused by novel pathogenic merbecoviruses.
Keywords: MERS-CoV; merbecovirus; neutralizing antibody; outbreak; pandemic; spillover.
. 2025 Jul 16:16:1593095.
doi: 10.3389/fmicb.2025.1593095. eCollection 2025. Cross-neutralization ability of anti-MERS-CoV monoclonal antibodies against a variety of merbecoviruses
Lin Pan # 1 , Yu Kaku # 1 , Jarel Elgin Tolentino 1 2 , Yusuke Kosugi 1 3 , Kei Sato 1 2 3 4 5 6 7
Affiliations
- PMID: 40740328
- PMCID: PMC12307460
- DOI: 10.3389/fmicb.2025.1593095
In the 21st century, three severe human coronavirus infections have occurred. One of them is the Middle East respiratory syndrome coronavirus (MERS-CoV), a merbecovirus belonging to the family Coronaviridae, is a human pathogenic coronavirus first detected in 2012. Several monoclonal antibodies (mAbs) have been developed for both therapeutics and prevention of MERS-CoV infection. However, the extent to which these anti-MERS-CoV antibodies neutralize other merbecoviruses remains unclear. Here, we evaluated the cross-neutralization ability of ten anti-MERS-CoV mAbs against the pseudoviruses with the spike proteins of five merbecoviruses known to bind to dipeptidyl peptidase 4 (DPP4): three clades of MERS-CoV, a bat-derived merbecovirus (BtCoV-422) and a pangolin-derived merbecovirus (MjHKU4r-CoV). We show that all eight mAbs targeting the receptor-binding domain (RBD) potently neutralize all MERS-CoV clades, but not BtCoV-422 and MjHKU4r-CoV. Of these, the neutralization potency of one mAb, m336, against the MERS-CoV clade B declined due to the V530L substitution detected in certain isolates during the 2015 outbreak in South Korea. On the other hand, although BtCoV-422 was neutralized by the two non-RBD mAbs, 7D10 (targeting the N-terminal domain) and G4 (targeting the S2 subunit), MjHKU4r-CoV found to be resistant. Our findings suggest that combining multiple mAbs targeting different epitopes could be a promising strategy for prevention of future outbreaks caused by novel pathogenic merbecoviruses.
Keywords: MERS-CoV; merbecovirus; neutralizing antibody; outbreak; pandemic; spillover.