SARS-CoV-2 structural coverage map reveals viral protein assembly, mimicry, and hijacking mechanisms

Area of Science:

• Virology
• Structural Biology
• Computational Biology

Background:

• Understanding the three-dimensional (3D) structure of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins is crucial for deciphering viral mechanisms.
• Existing structural data may be incomplete, leaving significant portions of the viral proteome unexplored.

Purpose of the Study:

• To generate comprehensive 3D structural models for the SARS-CoV-2 proteome.
• To identify regions of the viral proteome that mimic human proteins or are involved in host-pathogen interactions.
• To create a visualization tool for assessing the completeness of structural knowledge.

Main Methods:

• Computational modeling was used to generate 3D structures for SARS-CoV-2 proteins.
• Analysis of modeled structures to identify functional implications, such as mimicry of human proteins and host-hijacking mechanisms.
• Development of a structural coverage map to visualize known and unknown 3D structural information.
• Integration of models and the coverage map into an online resource, Aquaria-COVID.

Main Results:

• 2,060 3D models were generated, covering 69% of the SARS-CoV-2 proteome.
• Approximately 6% of the proteome showed mimicry of human proteins, and 7% was implicated in host-hijacking mechanisms.
• About 29% of the proteome formed heteromeric states, offering insights into viral replication complexes.
• A structural coverage map highlighted that 31% of the viral proteome remains structurally unknown ('dark').

Conclusions:

• The generated 3D models provide valuable structural details for SARS-CoV-2 proteins.
• The Aquaria-COVID resource enhances accessibility to structural data and identifies knowledge gaps.
• Understanding the structural basis of viral mechanisms is essential for combating coronavirus infections.