Structural insights into MERS and SARS coronavirus membrane proteins

Area of Science:

• Virology
• Structural Biology
• Drug Discovery

Background:

• The coronavirus membrane (M) protein is crucial for viral structure and pathogenesis.
• Developing broad-spectrum antivirals is challenging due to M protein sequence variability and limited structural data.

Purpose of the Study:

• To determine the structures of MERS-CoV M protein and SARS-CoV M protein.
• To identify structural differences and conserved features for antiviral development.

Main Methods:

• X-ray crystallography was used to obtain high-resolution (3-3.2 Å) structures.
• MERS-CoV M protein was engineered with a SARS-CoV-2-like antibody interface.
• SARS-CoV M protein structures were determined with and without the inhibitor JNJ-9676.

Main Results:

• First reported structures of human merbecovirus (MERS-CoV) M protein and SARS-CoV M protein.
• Detailed structural comparison between MERS-CoV, SARS-CoV, and SARS-CoV-2 M proteins.
• Insights into the conservation of the JNJ-9676 binding pocket and key differences were identified.

Conclusions:

• Structural insights into MERS-CoV and SARS-CoV M proteins can guide the design of targeted antivirals.
• Understanding conserved and divergent regions is key for developing broad-spectrum coronavirus M protein inhibitors.