Severe fever with thrombocytopenia syndrome virus(SFTSV)is a tick-borne virus that causes the severe fever thrombocytopenia syndrome,which manifests as fever and haemorrhage,accompanied by severe neurological complica...Severe fever with thrombocytopenia syndrome virus(SFTSV)is a tick-borne virus that causes the severe fever thrombocytopenia syndrome,which manifests as fever and haemorrhage,accompanied by severe neurological complications.To date,no specific antiviral drugs have been approved for this indication.Herein,we investigated whether vitamin D derivatives inhibit SFTSV both in vitro and in vivo.An in vitro study demonstrated that vitamin D derivatives significantly suppressed viral RNA replication,plaque formation,and protein expression in a dosedependent manner.Subsequently,in vivo studies revealed that doxercalciferol and alfacalcidol were associated with increased survival and reduced viral RNA load in the blood.Time-of-addition assay suggested that vitamin D derivatives primarily acted during the post-entry phase of SFTSV infection.However,cytopathic effect protective activity was not observed in RIG-I immunodeficient cell line Huh7.5,and the administration of vitamin D derivatives did not improve the survival rates or reduce the blood viral loads in adult A129 mice.Further transcriptome exploration into the antiviral mechanism revealed that alfacalcidol stimulates host innate immunity to exert antiviral effects.To expand the application of vitamin D derivatives,in vitro and in vivo drug combination assays were performed,which highlighted the synergistic effects of vitamin D derivatives and T-705 on SFTSV.The combination of alfacalcidol and T-705 significantly enhanced the therapeutic effects in mice.This study highlights the potential of vitamin D derivatives against SFTSV and suggests that they may have synergistic effects with other compounds used in the treatment of SFTSV infection.展开更多
基金supported by the National Natural Science Foundation of China(NSFC,grants 81773631,to R.C.grants 82304383 J.Y.)+1 种基金the National Science and Technology Major Projects for“Major New Drugs Innovation and Development”,China(2018ZX09711003,to W.Z.)the Hainan Provincial Natural Science Foundation of China(822QN299,to J.Y.).
文摘Severe fever with thrombocytopenia syndrome virus(SFTSV)is a tick-borne virus that causes the severe fever thrombocytopenia syndrome,which manifests as fever and haemorrhage,accompanied by severe neurological complications.To date,no specific antiviral drugs have been approved for this indication.Herein,we investigated whether vitamin D derivatives inhibit SFTSV both in vitro and in vivo.An in vitro study demonstrated that vitamin D derivatives significantly suppressed viral RNA replication,plaque formation,and protein expression in a dosedependent manner.Subsequently,in vivo studies revealed that doxercalciferol and alfacalcidol were associated with increased survival and reduced viral RNA load in the blood.Time-of-addition assay suggested that vitamin D derivatives primarily acted during the post-entry phase of SFTSV infection.However,cytopathic effect protective activity was not observed in RIG-I immunodeficient cell line Huh7.5,and the administration of vitamin D derivatives did not improve the survival rates or reduce the blood viral loads in adult A129 mice.Further transcriptome exploration into the antiviral mechanism revealed that alfacalcidol stimulates host innate immunity to exert antiviral effects.To expand the application of vitamin D derivatives,in vitro and in vivo drug combination assays were performed,which highlighted the synergistic effects of vitamin D derivatives and T-705 on SFTSV.The combination of alfacalcidol and T-705 significantly enhanced the therapeutic effects in mice.This study highlights the potential of vitamin D derivatives against SFTSV and suggests that they may have synergistic effects with other compounds used in the treatment of SFTSV infection.
