A team from China shares findings from a proteomic and metabolomic analysis of blood serum samples from individuals with or without COVID-19. Using liquid chromatography-tandem mass spec and other approaches, the researchers first profiled protein and metabolite features in serum samples from 46 COVID-19 patients and 53 unaffected controls, identifying dozens of proteins and more than 200 metabolites with altered expression in severe COVID-19 cases. Along with clues to the pathways altered in individuals with more dangerous SARS-CoV-2 infections, metabolite and protein profiles from these and other cases and controls helped the authors establish a machine learning method for classifying COVID-19 cases. "We demonstrated the potential of identifying COVID-19 patients who may eventually become severe cases based on analysis of a panel of serum proteins and metabolites," they write. "Our data offer a landscape view of blood molecular changes induced by SARS-CoV-2 infection, which may provide useful diagnostic and therapeutic clues in the ongoing battle against the COVID-19 pandemic."
Researchers from the US, UK, France, and Germany present a phosphoproteomics-focused analysis of SARS-CoV-2 infections in an African green monkey cell line. That team's quantitative mass spec-based analysis revealed changes in protein levels during SARS-CoV-2 infection, along with pronounced changes in signaling pathway activity and phosphorylation network organization that were used in subsequent drug target searches. "The unbiased, global phosphoproteomics approaches used here highlight cellular processes hijacked during SARS-CoV-2 infection," the authors report, adding that "we employed a data-driven approach by mapping phosphorylation profiles of dysregulated signaling pathways to drugs and compounds targeting those signaling pathways."
Finally, an international team led by investigators at the Lunenfeld-Tanenbaum Research Institute and the University of Toronto reports on DNA damage responses found in a human cell line using CRISPR-Cas9 gene editing screens in combination with DNA-damaging genotoxic compounds. Based on results from 31 CRISPR-Cas9 screens and exposures to more than two dozen DNA-damaging drugs, the researchers highlighted nearly 900 genes that appeared to influence response to the genotoxic compounds, leading to enhanced sensitivity or resistance. By digging into that set, they saw a non-homologous end-joining pathway role for a gene called ERCC6L2 that was previously implicated in bone marrow failure syndrome, for example, while identifying potential DNA repair genes not reported in the past and getting new insights into drug mechanisms and metabolism.