Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the most important emerging pathogen worldwide, but its early transcriptional dynamics and host immune response remain unclear. Herein, the expression profiles of viral interactions with different types of hosts were comprehensively dissected to shed light on the early infection strategy of SARS-CoV-2 and the host immune response against infection. SARS-CoV-2 was found to exhibit a two-stage transcriptional strategy within the first 24 h of infection, comprising a lag phase that ends with the virus being paused and a log phase that starts when the viral load increases rapidly. Interestingly, the host innate immune response was found not to be activated (latent period) until the virus entered the log stage. Noteworthy, when intracellular immunity is suppressed, SARS-CoV-2 shows a correlation with dysregulation of metal ion homeostasis. Herein, the inhibitory activity of copper ions against SARS-CoV-2 was further validated in in vitro experiments. Coronavirus disease 2019-related genes (including CD38, PTX3, and TCN1) were also identified, which may serve as candidate host-restricted factors for interventional therapy. Collectively, these results confirm that the two-stage strategy of SARS-CoV-2 effectively aids its survival in early infection by regulating the host intracellular immunity, highlighting the key role of interferon in viral infection and potential therapeutic candidates for further investigations on antiviral strategies.