Fig. 1

Zoledronic acid (ZA) acts as immunostimulant and endosomal disruptor of dendritic cell in SARS-CoV-2 infection. Inhaled SARS-CoV-2 particles are internalized by the DC (top). In COVID-19 disease, there is depletion of γδ T cells (bottom-left). In addition, virion release depends on prenylation signaling derived from the mevalonate pathway. On the other hand, ZA (bottom-right) inhibits the conversion of geranyl pyrophosphate (GPP) to farnesyl pyrophosphate (FPP), increasing the concentrations of isopentenyl pyrophosphate (IPP). Release of IPP induces γ9δ2 T-cell expansion by phosphoantigen recognition, mediated by butyrophilin-presentation. Downstream inhibition of prenylation reduces the activity of GTPases, decreasing the release of SARS-CoV-2. ZA also affects differentiation of the DC with downregulation of the expression of CD1a, CD11c, CD83, CD86, DC-SIGN, and HLA-DR and enhancement of the expression of CD80. Figure was created using BioRender https://biorender.com/