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Life sciences · Journal article
Journal of General Virology · July 15, 2026
Encouraging direction, but not yet definitive.
This is a mechanistic cell-based study establishing that endolysosomal two-pore channels (TPC1 and TPC2) are host factors required for enterovirus replication across multiple serotypes, acting through NAADP-dependent calcium signalling to regulate endosomal trafficking rather than viral binding or translation. The findings suggest TPCs are a potential broad-spectrum antiviral target, but the work is limited to cultured cells and does not provide evidence of in vivo efficacy or clinical benefit.
In vitro mechanistic study with CRISPR/Cas9 knockouts, pharmacological inhibition, live-cell calcium imaging, and transcriptomic profiling. Cultured human cells infected with enterovirus 71 and other enterovirus serotypes. Intervention: CRISPR/Cas9 knockout of TPC1 or TPC2, or pharmacological inhibition of NAADP-evoked Ca²⁺ signalling; cepharanthine treatment. Compared with: Wild-type or control-treated cells.
Pharmacological inhibition or CRISPR knockout of TPC1 or TPC2 significantly suppressed enterovirus 71 replication TPC loss delayed viral progression through early and late endosomal compartments without affecting viral binding, internalization, RNA translation or replication TPC-dependent NAADP signalling is necessary for endolysosomal Ca²⁺ release during infection, confirmed by live-cell imaging
No human clinical trials or data on safety and efficacy in patients Pharmacological inhibition or CRISPR knockout of TPC1 or TPC2 significantly suppressed enterovirus 71 replication
This identifies a potential host target for broad-spectrum antiviral therapy against enteroviruses, a family lacking current effective treatments. However, in vivo efficacy and clinical safety have not yet been demonstrated, and the findings require validation in animal models and eventual clinical trials before clinical use can be considered.
A mechanistic study identifying host factors and a potential drug target for enterovirus infection using cell-based assays and knockout models, with broad-spectrum activity but lacking in vivo efficacy or clinical outcome data.
As stated by the source record.
This identifies a potential host target for broad-spectrum antiviral therapy against enteroviruses, a family lacking current effective treatments. However, in vivo efficacy and clinical safety have not yet been demonstrated, and the findings require validation in animal models and eventual clinical trials before clinical use can be considered.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
What is missing. This record has no reported figures. That is a gap in the analysis, not a judgement about the study.
Enteroviruses are significant human pathogens for which there are currently no effective antiviral therapies available. Two-pore channels (TPCs) are endolysosomal cation channels activated by nicotinic acid adenine dinucleotide phosphate (NAADP). These channels play a crucial role in regulating vesicular calcium (Ca²⁺) signalling and endolysosomal membrane trafficking. While endolysosomal TPCs have been implicated in the infectivity of some enveloped viruses, their role in non-enveloped virus infections remains unclear. In this study, we identify human TPC isoforms TPC1 and TPC2 as essential host factors that enhance enterovirus infection by regulating endolysosomal trafficking. Inhibiting NAADP-evoked Ca²⁺ signalling pharmacologically or using CRISPR/Cas9 to knockout either TPC isoform significantly suppressed the replication of enterovirus 71. Mechanistically, the loss of TPC function did not affect the viral binding, internalization or post-entry RNA translation and replication; instead, it delayed the viral progression through early and late endosomal compartments. Live-cell Ca²⁺ imaging confirmed that TPC-dependent NAADP signalling is necessary for endolysosomal Ca²⁺ release during infection. Our data also suggest cepharanthine, a bisbenzylisoquinoline alkaloid, inhibits enterovirus infection partly by modulating TPC-mediated Ca 2+ signalling. Notably, the pharmacological inhibition or depletion of TPCs broadly restricted the replication of various enterovirus serotypes. Transcriptomic profiling revealed that the disruption of TPC1 or TPC2 alters gene networks associated with endocytosis and vesicular trafficking, emphasizing the vital role of TPCs in maintaining endolysosomal homeostasis. In summary, these findings establish TPC-dependent Ca 2+ signalling as a conserved host pathway that enteroviruses exploit and highlight endolysosomal TPCs as promising targets for the development of broad-spectrum antiviral strategies.
Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.