A group from Key Laboratory of the Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western, China, etc. has reported a novel mechanism of SARS-CoV-2 infection in the presence of fever.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210595/
Transient receptor potential vanilloid 2 (TRPV2) was originally isolated as a molecule sensitive to temperatures. TRPV2 plays an important role in innate immunity and is mainly distributed in the endoplasmic reticulum in the absence of stimulation. Under certain stimulatory conditions, such as stimulation by chemokines, growth factors, or stress conditions, TRPV2 can be transferred from the endoplasmic reticulum to the cell membrane to promote Ca2+ entry into the cell and accumulation in pseudopodia, which can promote the migration of macrophages towards an inflamed area and promote the phagocytic function of macrophages.
It was examined if TRPV2 was involved in SARS-CoV-2 infection. The interaction between TRPV2 and SARS-CoV-2 Spike was examined at 37 °C and 39.5 °C with co-IP assays using PBAMs, human THP-1 cells, and mouse macrophages (RAW264.7) as host cells. As shown below, the co-IP analysis confirmed the interaction between TRPV2 and SARS-CoV-2 Spike occurs at 39.5 °C but not at 37 °C.
The febrile temperature (39.5 °C) significantly enhanced the expression of macrophage-secreted cytokines, including IFN-α, IFN-γ, IL-13, IL-α, TNF-α, IL-10, IL-18, IL-2, IL-4, IL-17A, MCP-1, and IL-15, and further it was confirmed that the increased cytokine secretion was independent from existence of ACE2 and Neuropilin-1 at 39.5C.
Then, it was tested whether an inhibitor of TRPV2 (SKF-96365) could suppress such cytokine release or not, and it was confirmed that SKF-96365 effectively suppresses the cytokine storm caused by SARS-CoV-2 in the presence of fever.
Thus, authors discovered a novel mechanism of SARS-CoV-2 infection of macrophages and showed that SKF-96365 is potential candidate for treating SARS-CoV2 in febrile conditions.
