Establishment of a Sandwich ELISA for Detection of Pan-Merbecoviruses

<i>Merbecovirus</i>, a subgenus of <i>Betacoronavirus</i>, includes MERS-CoV and multiple bat-derived viruses with zoonotic potential. Given the unpredictable emergence of these viruses and their genetic diversity, development of broad-spectrum diagnostic tools is expected. I...

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Main Authors: Kaixin Li, Misa Katayama, Ayano Ichikawa, Hiromichi Matsugo, Yuta Wakabayashi, Akiko Takenaka-Uema, Wataru Sekine, Taisuke Horimoto, Shin Murakami
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Pathogens
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Online Access:https://www.mdpi.com/2076-0817/14/6/605
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author Kaixin Li
Misa Katayama
Ayano Ichikawa
Hiromichi Matsugo
Yuta Wakabayashi
Akiko Takenaka-Uema
Wataru Sekine
Taisuke Horimoto
Shin Murakami
author_facet Kaixin Li
Misa Katayama
Ayano Ichikawa
Hiromichi Matsugo
Yuta Wakabayashi
Akiko Takenaka-Uema
Wataru Sekine
Taisuke Horimoto
Shin Murakami
author_sort Kaixin Li
collection DOAJ
description <i>Merbecovirus</i>, a subgenus of <i>Betacoronavirus</i>, includes MERS-CoV and multiple bat-derived viruses with zoonotic potential. Given the unpredictable emergence of these viruses and their genetic diversity, development of broad-spectrum diagnostic tools is expected. In this study, we established a sandwich ELISA targeting the nucleocapsid (N) protein of merbecoviruses. We generated monoclonal antibodies (mAbs) using recombinant N protein of a bat merbecovirus, VsCoV-1, and selected cross-reactive clones for other merbecoviruses. Three mAbs showed strong reactivities with multiple merbecoviruses but not with SARS-CoV-2 or endemic human coronaviruses. Pairwise ELISA screening identified 1A8/10H6 mAbs as the optimal combination for detection of N protein from six merbecoviruses—VsCoV-1, EjCoV-3, MERS-CoV, NeoCoV, HKU4, and HKU5—with limits of detection (LODs) below 7.81 ng/mL, including 1.25 ng/mL for VsCoV-1. Infectious bat merbecovirus EjCoV-3 was detected at 1.3 × 10<sup>3</sup> PFU/mL. No cross-reactivity was observed with non-merbecoviruses, indicating its high specificity. This sandwich ELISA offers a rapid, reproducible, and cost-effective diagnostic platform with potential for high-throughput screening and automation. Moreover, its design is amenable to adaptation into point-of-care formats such as lateral flow assays, highlighting its value for field-based surveillance and pandemic preparedness.
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institution Kabale University
issn 2076-0817
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publishDate 2025-06-01
publisher MDPI AG
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spelling doaj-art-e6bb3e315ea6444d9dec24cf4fabe1202025-08-20T03:27:36ZengMDPI AGPathogens2076-08172025-06-0114660510.3390/pathogens14060605Establishment of a Sandwich ELISA for Detection of Pan-MerbecovirusesKaixin Li0Misa Katayama1Ayano Ichikawa2Hiromichi Matsugo3Yuta Wakabayashi4Akiko Takenaka-Uema5Wataru Sekine6Taisuke Horimoto7Shin Murakami8Laboratory of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, JapanLaboratory of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, JapanLaboratory of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, JapanLaboratory of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, JapanLaboratory of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, JapanLaboratory of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, JapanLaboratory of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, JapanLaboratory of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, JapanLaboratory of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan<i>Merbecovirus</i>, a subgenus of <i>Betacoronavirus</i>, includes MERS-CoV and multiple bat-derived viruses with zoonotic potential. Given the unpredictable emergence of these viruses and their genetic diversity, development of broad-spectrum diagnostic tools is expected. In this study, we established a sandwich ELISA targeting the nucleocapsid (N) protein of merbecoviruses. We generated monoclonal antibodies (mAbs) using recombinant N protein of a bat merbecovirus, VsCoV-1, and selected cross-reactive clones for other merbecoviruses. Three mAbs showed strong reactivities with multiple merbecoviruses but not with SARS-CoV-2 or endemic human coronaviruses. Pairwise ELISA screening identified 1A8/10H6 mAbs as the optimal combination for detection of N protein from six merbecoviruses—VsCoV-1, EjCoV-3, MERS-CoV, NeoCoV, HKU4, and HKU5—with limits of detection (LODs) below 7.81 ng/mL, including 1.25 ng/mL for VsCoV-1. Infectious bat merbecovirus EjCoV-3 was detected at 1.3 × 10<sup>3</sup> PFU/mL. No cross-reactivity was observed with non-merbecoviruses, indicating its high specificity. This sandwich ELISA offers a rapid, reproducible, and cost-effective diagnostic platform with potential for high-throughput screening and automation. Moreover, its design is amenable to adaptation into point-of-care formats such as lateral flow assays, highlighting its value for field-based surveillance and pandemic preparedness.https://www.mdpi.com/2076-0817/14/6/605bat merbecovirusessandwich ELISAantigen detectionmonoclonal antibody
spellingShingle Kaixin Li
Misa Katayama
Ayano Ichikawa
Hiromichi Matsugo
Yuta Wakabayashi
Akiko Takenaka-Uema
Wataru Sekine
Taisuke Horimoto
Shin Murakami
Establishment of a Sandwich ELISA for Detection of Pan-Merbecoviruses
Pathogens
bat merbecoviruses
sandwich ELISA
antigen detection
monoclonal antibody
title Establishment of a Sandwich ELISA for Detection of Pan-Merbecoviruses
title_full Establishment of a Sandwich ELISA for Detection of Pan-Merbecoviruses
title_fullStr Establishment of a Sandwich ELISA for Detection of Pan-Merbecoviruses
title_full_unstemmed Establishment of a Sandwich ELISA for Detection of Pan-Merbecoviruses
title_short Establishment of a Sandwich ELISA for Detection of Pan-Merbecoviruses
title_sort establishment of a sandwich elisa for detection of pan merbecoviruses
topic bat merbecoviruses
sandwich ELISA
antigen detection
monoclonal antibody
url https://www.mdpi.com/2076-0817/14/6/605
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