Structural insights into MERS and SARS coronavirus membrane proteins
The membrane (M) protein of coronaviruses is essential for maintaining structural integrity during membrane virion budding and viral pathogenesis. Given its high conservation in lineages within the betacoronavirus genus, such as sarbecoviruses, the M protein presents as an attractive therapeutic target; however, developing broad-spectrum antivirals targeting coronaviruses such as MERS-CoV is challenging due to lower sequence conservation and limited structural information available beyond that of the SARS-CoV-2 M protein. In this study, we report 3-3.2 Å resolution structures of MERS-CoV M protein, engineered with a SARS-CoV-2-like antibody interface, representing the first human merbecovirus M protein structure, and SARS-CoV M protein structures, with and without a previously identified SARS-CoV-2 M protein inhibitor, JNJ-9676. We highlight the structural differences between the MERS-CoV, SARS-CoV and SARS-CoV-2 M proteins, and present insights into the conservation of the JNJ-9676 binding pocket as well as key differences that could be targeted to accelerate the design of specific MERS-CoV and broad-spectrum antivirals targeting coronavirus M proteins.
Authors
- Michiel Van Gool (ORCID: https://orcid.org/0000-0001-5424-1377)
- Eric J. Snijder (ORCID: https://orcid.org/0000-0003-3297-2309)
- Pravien Abeywickrema (ORCID: https://orcid.org/0009-0008-1017-0384)
- Xiaodi Yu (ORCID: https://orcid.org/0000-0001-7520-0646)
- Yanting Yin (ORCID: https://orcid.org/0000-0001-9310-1094)
- Jiexiong Xie (ORCID: https://orcid.org/0000-0002-3374-6605)
- Sujata Sharma (ORCID: https://orcid.org/0000-0002-7588-2939)
- Nick Van den Broeck (ORCID: https://orcid.org/0000-0001-5900-4813)
- Heidi L. M. De Gruyter
- Marnix Van Loock (ORCID: https://orcid.org/0000-0003-4151-4588)
- Mandeep Mann (ORCID: https://orcid.org/0000-0002-8252-6107)
- Robyn Miller
- Ellen Van Damme (ORCID: https://orcid.org/0000-0003-1808-9851)
- Martijn J. van Hemert (ORCID: https://orcid.org/0000-0002-2617-9243)
- Simone Marsili (ORCID: https://orcid.org/0000-0001-6284-6122)
- Jordi Doijen (ORCID: https://orcid.org/0000-0002-1707-0174)
- Christopher K. Kariuki (ORCID: https://orcid.org/0000-0001-6596-9304)
- Anouk A. Leijs
- Madison Piassek
- Anil Koul
- Ken Keustermans
Institutions
- Johnson & Johnson (United States) (US)
- Leiden University Medical Center (NL)
Publication Details
- Journal
- Communications Biology
- Published
- 2025-11-24
- DOI
- https://doi.org/10.1038/s42003-025-09042-3
- Citations
- 2
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 2.79
Funders
- Biomedical Advanced Research and Development Authority