Table 1 Mechanisms and current evidence about fields of SARS-CoV-2 characterization and entry reported for specific omics data: a) viral genomics and proteomics; b) host-virus interactions at multi-omics levels

Genome evolution and geographical distribution

Evolutionary history of SARS-CoV-2 reconstructed by a phylogenetic approach among the 5 subgenera of Betacoronaviruses [TE01-TE03]

At the beginning of pandemic SARS-CoV-2 genomes were classified into 5 main clades: S84, V251, I378, D392, and G61 (the most frequent ancestral type) [TE04-TE05]

Genomic hotspots for mutation, drivers of evolution and correlation with pathogenesis

In SARS-CoV-2 genomes: 10 hyper-variable genomic hotspots [TE14]

Genomic regions encoding nsps, except nsp11, had values of dN/dS ratio < 1. Among the structural genes, only S and M displayed dN/dS < 1. Deletions in ORF7b and ORF8 of SARS-CoV-2 genome confer lower odds of developing hypoxia in infected hosts [TE09; TE12]

Intra-host genomic variability

Small- and large-scale intra-host variations [TE19-TE20]

Spatial–temporal redistribution of variants in respiratory and gastro-intestinal tract [TE19-TE21]

Single viral proteins

Two mutations in nsp6 and in a region near ORF10 confer lower stability to S, N, M, E proteins, linked to autophagy. [TE24-TE25]

Non-conservative substitutions in functional regions of the S, nsp1 and nsp3 may contribute to separate SARS-CoV and SARS-CoV-2 in spread and virulence [TE27]

Whole viral proteome

Dynamicome study, based on Viral Integrated Structural Dynamic Database (VIStEDD), among 273 virus/host PP interactions highlighted 6 major viral nodes influencing the activity of 166 host nodes involved in various cellular processes [TE28-TE29]

Immune proteomics

Viral proteomics was used to design multi-epitope vaccines and to find possible host–pathogen molecular mimicry [TE31]

Viral RNA and protein interactions

9 potential silencer RNA (siRNA) targets, conserved among all the studied SARS-CoV-2 genomes. [TE32]

3 SARS-CoV small viral (sV) RNAs involved in lung pathology of mice. [TE33]

In Vero E6 and to Huh-7 cells infected by SARS-CoV-2, 163 and 229 host protein bind SARS-CoV-2 RNA. [TE37]

GO enrichment analysis revealed that most of the proteins were protective from virus-induced cell death, regulating SARS-CoV-2 pathogenicity. [TE38]

Functional analysis discovered novel proviral genes and pathways, including chromatin remodelling complexes [TE33-TE39]

Virus–host protein–protein interactions

1311 PPIs were used to build a large coronavirus-host interactome. Relevant small protein complexes:

 EIF4E2-GIGYF2 dimer, involved in proteins translation repression and the MAT2A-MAT2B complex [TE42];

 DNA-PK kinase contributing to interferon induction [TE42];

 Mitochondrial proteins PHB, PHB2 and STOML2, regulating mitophagy. [TE42]

 Host interactome linked to S of SARS-CoV and MERS-CoV: innate immunity involved. [TE43]

The International Molecular Exchange (IMEx) Consortium cured a dataset of PPI, contained interactions of SARS-CoV-2 and SARS-CoV, with human proteins [TE44]

Multilayer virus–host interactions

Multilayer analysis, in few cases may predict different SARS-CoV-2 disease phenotypes:

 Immune regulation appears to be linked to gene TMPRSS2, involved in SARS-CoV-2 virus entry [TE52]

 SARS-CoV-2 transcripts detectable only in BAL from severe COVID-19 patients. [TE53]

 SARS-CoV-2 transcripts strongly enriched in ciliated and epithelial progenitor cell population and in the SPP1 + macrophage population. [TE53]

Master Regulator Analysis on multiple datasets showed that SARS-CoV-2 mainly affected:

 Apoptotic and mitochondrial mechanisms [TE49]

 ACE2 protein receptor regulation [TE49]

 COVID-19 Disease Map, an open-access repository containing ordered molecular interaction diagrams, implicated in the disease. It is available on website [TE50]

Virus–host receptor interaction

Interactome of 45 proteins connected to four cell surface seed proteins (ATP6V1A, AP3B1, STOM, and ZDHHC5) with physical affinity to viral S,E and M proteins. [TE73]

 7 miRNA (miR-124-3p, let-7 g-5p, miR-133a-3p, miR-133b, miR-218-5p, miR-22-3p, and miR-506-3p) interconnect with proteins involved in viral entry and replication process. [TE73]

A probabilistic modelling using iDREM (interactive Dynamic Regulatory Events Miner) revealed:

63 significant regulators expressed in SARS-CoV-2 infected Calu-3 cells (14 also identified analysing the transcriptome of PBMC and Broncho-alveolar cells)

An interactome involved in viral entry, including prohibition (PHB) as alternative receptor or co-receptor [TE48]