Abstract
Envelope viruses infecting human individuals can originate from two sources: either from an intermediary animal that transmits the virus to humans, or from another infected human. During a pandemic such as SARS-CoV-2, identifying the intermediate host or the primary human source presents a significant challenge. This complex task is typically addressed through genetics-based approaches, including metagenomic analysis, phylogenetic and phylodynamic rooting methods, integrated with epidemic simulations. We propose a novel method to investigate these primary viral sources. During their replication cycle, envelope viruses hijack materials from host cellular compartments such as the endoplasmic reticulum (ER), the Golgi apparatus (GA) and the ER-Golgi intermediate compartment (ERGIC). Biochemical, morphological, and functional differences in the membranes of ER, GA, and ERGIC can be detected not only across mammalian species but also among individual humans. These variations arise from a complex interplay of genetic, epigenetic, metabolic, environmental, and age-related factors. We propose utilizing lipidomics to identify unique lipid signatures in the compositions of the viral envelopes that are co-opted from the host cell’s organelles. Since interspecies and interhuman lipidic differences could significantly impact the composition of viral envelopes derived from host membranes, molecular disparities might serve as critical markers for tracing the source of viral particles. This approach could enable the identification not only of the mammalian sources of human spillover, but also provide insights into the age, medical condition, genetics, and ethnic background of the first human host.