A SARS-CoV-2 -human metalloproteome interaction map

Area of Science:

• Biochemistry
• Virology
• Structural Biology

Background:

• The COVID-19 pandemic, caused by SARS-CoV-2, presents a significant global health challenge.
• Understanding the molecular interactions between SARS-CoV-2 and human proteins is crucial for developing effective countermeasures.
• Limited information exists regarding the association of SARS-CoV-2 with human metalloproteins.

Purpose of the Study:

• To identify human metalloproteins that physically interact with SARS-CoV-2.
• To investigate the role of specific metal ions, particularly zinc (Zn2+), in SARS-CoV-2-host interactions.
• To explore potential links between these interactions and severe COVID-19 outcomes.

Main Methods:

• Utilized a structure-based approach to identify metalloproteins from experimentally validated SARS-CoV-2-human protein-protein interaction datasets.
• Analyzed the metal ion content within the identified human metalloproteome.
• Investigated molecular linkages between the identified zinc-binding proteome and pre-existing medical conditions associated with severe COVID-19.

Main Results:

• Identified 58 human metalloproteins interacting with SARS-CoV-2.
• Found that most interacting human metalloproteins bind to the SARS-CoV-2 orf8 protein.
• Demonstrated a significantly higher proportion of zinc (Zn2+)-binding proteins compared to other metal-binding proteins in the interacting human metalloproteome.
• Established a molecular link between the human zinc-binding proteome and medical conditions increasing COVID-19 severity risk.

Conclusions:

• SARS-CoV-2 interacts with a significant number of human metalloproteins, particularly through the orf8 protein.
• Zinc (Zn2+) plays a critical role in the SARS-CoV-2-human interaction.
• SARS-CoV-2 infection may perturb host cellular metal homeostasis, potentially contributing to severe COVID-19.
• The findings highlight potential therapeutic targets related to metal ion homeostasis.