Structural insights into MERS and SARS coronavirus membrane proteins

Communications Biology, vol. 8, pp. 1651

Abstract

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 21

1. Mandeep Kaur Mann

   Johnson & Johnson (United States)

   Affiliation as printed

   Johnson and Johnson, Spring House, PA, USA

2. Yanting Yin

   Johnson & Johnson (United States)

   Affiliation as printed

   Johnson and Johnson, Spring House, PA, USA

3. Simone Marsili
   Affiliation as printed

   Johnson and Johnson, Toledo, Spain

4. Jiexiong Xie

   Johnson & Johnson (United States)

   Affiliation as printed

   Johnson and Johnson, Beerse, Belgium

5. Jordi Doijen

   Johnson & Johnson (United States)

   Affiliation as printed

   Johnson and Johnson, Beerse, Belgium

6. Robyn Miller

   Johnson & Johnson (United States)

   Affiliation as printed

   Johnson and Johnson, Spring House, PA, USA

7. Madison Piassek

   Johnson & Johnson (United States)

   Affiliation as printed

   Johnson and Johnson, Spring House, PA, USA

8. Nick Van den Broeck
   Affiliation as printed

   Charles River Laboratories, Beerse, Belgium

9. Christopher Kinyanjui Kariuki

   Johnson & Johnson (United States)

   Affiliation as printed

   Johnson and Johnson, Beerse, Belgium

10. Heidi L. M. De Gruyter Aachen Molecular Virology Laboratory

    Leiden University · Leiden University Medical Center

    Affiliation as printed

    Molecular Virology Laboratory, Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, Leiden, the Netherlands

11. Anouk A. Leijs Aachen Molecular Virology Laboratory

    Leiden University · Leiden University Medical Center

    Affiliation as printed

    Molecular Virology Laboratory, Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, Leiden, the Netherlands

12. Eric J. Snijder Aachen Molecular Virology Laboratory

    Leiden University · Leiden University Medical Center

    Affiliation as printed

    Molecular Virology Laboratory, Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, Leiden, the Netherlands

13. Martijn J. van Hemert Aachen Molecular Virology Laboratory

    Leiden University · Leiden University Medical Center

    Affiliation as printed

    Molecular Virology Laboratory, Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, Leiden, the Netherlands

14. Ken Keustermans
    Affiliation as printed

    Charles River Laboratories, Beerse, Belgium

15. Michiel Van Gool
    Affiliation as printed

    Johnson and Johnson, Toledo, Spain

16. Xiaodi Yu

    Johnson & Johnson (United States)

    Affiliation as printed

    Johnson and Johnson, Spring House, PA, USA

17. Marnix Van Loock

    Johnson & Johnson (United States)

    Affiliation as printed

    Johnson and Johnson, Beerse, Belgium

18. Anil Koul

    Johnson & Johnson (United States)

    Affiliation as printed

    Johnson and Johnson, Beerse, Belgium

19. Sujata Sharma

    Johnson & Johnson (United States)

    Affiliation as printed

    Johnson and Johnson, Spring House, PA, USA

20. Ellen Van Damme

    Johnson & Johnson (United States)

    Affiliation as printed

    Johnson and Johnson, Beerse, Belgium

21. Pravien D. Abeywickrema corresponding

    Johnson & Johnson (United States)

    Affiliation as printed

    Johnson and Johnson, Spring House, PA, USA. pabeywic@its.jnj.com