Abstract The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a global threat to human health and has compromised economic stability. In addition to the development of an effective vaccine, it is imperative to understand how SARS‐CoV‐2 hijacks host cellular machineries on a system‐wide scale so that potential host‐directed therapies can be developed. In situ proteome‐wide abundance and thermal stability measurements using thermal proteome profiling (TPP) can inform on global changes in protein activity. Here we adapted TPP to high biosafety conditions amenable to SARS‐CoV‐2 handling. We discovered pronounced temporal alterations in host protein thermostability during infection, which converged on cellular processes including cell cycle, microtubule and RNA splicing regulation. Pharmacological inhibition of host proteins displaying altered thermal stability or abundance during infection suppressed SARS‐CoV‐2 replication. Overall, this work serves as a framework for expanding TPP workflows to globally important human pathogens that require high biosafety containment and provides deeper resolution into the molecular changes induced by SARS‐CoV‐2 infection. Thermal proteome profiling (TPP) measurements of protein state and interaction changes in SARS‐CoV‐2 infection reveal pronounced temporal alterations in host protein thermostability during infection and indicate druggable host targets.
【저자키워드】 SARS‐CoV‐2, Microbiology, Virology & Host Pathogen Interaction, aryl hydrocarbon hydroxylase, heat shock chaperone, rhapontigenin, tanespimycin, 【초록키워드】 Vaccine, coronavirus, therapy, Infection, severe acute respiratory syndrome Coronavirus, cell cycle, SARS‐CoV‐2, biosafety, Replication, Protein, Health, stability, Pathogens, targets, RNA splicing, proteome, molecular, respiratory, change, thermal stability, cellular, host proteins, Interaction, framework, acute respiratory syndrome, Regulation, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, alteration, abundance, host protein, human pathogen, SARS‐CoV‐2 infection, handling, microtubule, cellular processes, thermal, Host, effective, Cell, addition, provide, condition, changes in, imperative, suppressed, displaying, cellular processe, global change, 【제목키워드】 host protein,