Feline infectious peritonitis virus (FIP virus: FIPV), a feline coronavirus of 
the family Coronaviridae, causes a fatal disease called FIP in wild and domestic 
cat species. The genome of coronaviruses encodes a hydrophobic transmembrane 
protein, the envelope (E) protein. The E protein possesses ion channel activity. 
Viral proteins with ion channel activity are collectively termed "viroporins". 
Hexamethylene amiloride (HMA), a viroporin inhibitor, can inhibit the ion 
channel activity of the E protein and replication of several coronaviruses. 
However, it is not clear whether HMA and other viroporin inhibitors affect 
replication of FIPV. We examined the effect of HMA and other viroporin 
inhibitors (DIDS [4,4'-disothiocyano-2,2'-stilbenedisulphonic acid] and 
amantadine) on infection by FIPV serotypes I and II. HMA treatment drastically 
decreased the titers of FIPV serotype I strains Black and KU-2 in a 
dose-dependent manner, but it only slightly decreased the titer of FIPV serotype 
II strain 79-1146. In contrast, DIDS treatment decreased the titer of FIPV 
serotype II strain 79-1146 in dose-dependent manner, but it only slightly 
decreased the titers of FIPV serotype I strains Black and KU-2. We investigated 
whether there is a difference in ion channel activity of the E protein between 
viral serotypes using E. coli cells expressing the E protein of FIPV serotypes I 
and II. No difference was observed, suggesting that a viroporin other than the E 
protein influences the differences in the actions of HMA and DIDS on FIPV 
serotypes I and II.