Identifying and profiling structural similarities between Spike of SARS-CoV-2 and other viral or host proteins with Machaon.
Panos KakoulidisIoannis S VlachosDimitris ThanosGregory L BlatchIoannis Z EmirisEma AnastasiadouPublished in: Communications biology (2023)
Using protein structure to predict function, interactions, and evolutionary history is still an open challenge, with existing approaches relying extensively on protein homology and families. Here, we present Machaon, a data-driven method combining orientation invariant metrics on phi-psi angles, inter-residue contacts and surface complexity. It can be readily applied on whole structures or segments-such as domains and binding sites. Machaon was applied on SARS-CoV-2 Spike monomers of native, Delta and Omicron variants and identified correlations with a wide range of viral proteins from close to distant taxonomy ranks, as well as host proteins, such as ACE2 receptor. Machaon's meta-analysis of the results highlights structural, chemical and transcriptional similarities between the Spike monomer and human proteins, indicating a multi-level viral mimicry. This extended analysis also revealed relationships of the Spike protein with biological processes such as ubiquitination and angiogenesis and highlighted different patterns in virus attachment among the studied variants. Available at: https://machaonweb.com .
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- endothelial cells
- amino acid
- protein protein
- binding protein
- copy number
- gene expression
- single cell
- lymph node
- high resolution
- transcription factor
- genome wide
- dna methylation
- angiotensin ii
- small molecule
- mass spectrometry
- vascular endothelial growth factor
- heat stress
- angiotensin converting enzyme
- data analysis
- wound healing
- disease virus