Identification and evaluation of Nordihydroguaiaretic acid (NDGA) as an active traditional Chinese medicine compound inhibiting the 3C-like protease of feline infectious peritonitis virus.

Feline infectious peritonitis (FIP) is a systemic and fatal disease that poses a serious threat to feline population, underscoring the urgent need for development of novel antiviral drugs. The FIP is caused by the feline infectious peritonitis virus (FIPV), a highly pathogenic feline coronavirus (FCoV), and 3C-like protease (3CLpro) is a critical drug target in coronaviruses. Here, we employed structure-based in silico screening and identified Nordihydroguaiaretic acid (NDGA), a bioactive compound used in traditional Chinese medicine, as a potential FIPV 3CLpro inhibitor. Enzymatic assays confirmed that NDGA effectively inhibits FIPV 3CLpro activity. Furthermore, cellular assays demonstrated that NDGA suppresses FIPV replication. Additionally, in a feline challenge model with an FCoV-II strain, NDGA treatment prolonged survival and improved clinical outcomes. These results support NDGA as a potential lead compound for FIP therapy.