Halofuginone, sold under the brand name Halocur, is a coccidiostat used in veterinary medicine. It is a synthetic halogenated derivative of febrifugine, a natural quinazolinone alkaloid which can be found in the Chinese herb Dichroa febrifuga (Chang Shan).[1] Collgard Biopharmaceuticals is developing halofuginone for the treatment of scleroderma and it has received orphan drug designation from the U.S. Food and Drug Administration.[2]
EPRS1 acts, in human cells, as a proviral factor in mammarenaviruses infection, including LCMV, JUNV, and LASV, and its inhibition using halofuginon compound, a prolyl domain inhibitor, completely abolishes the viral infection by interrupting viral assembly and budding.[3]
Halofuginone inhibits the development of T helper 17 cells, immune cells that play an important role in autoimmune disease, but it does not affect other kinds of T cells which are involved in normal immune function.[4] Halofuginone therefore has potential for the treatment of autoimmune disorders.
Halofuginone is also an inhibitor of collagen type I gene expression and as a consequence it may inhibit tumor cell growth. Halofuginone exerts its effects by acting as a high affinity inhibitor of the enzyme glutamyl-prolyl tRNA synthetase. Inhibition of prolyl tRNA charging leads to the accumulation of uncharged prolyl tRNAs, which serve as a signal to initiate the amino acid starvation response, which in turn exerts anti-inflammatory and anti-fibrotic effects.[5]
