Antiviral Activity of Diltiazem HCl Against Pseudorabies Virus Infection In Vitro

Pseudorabies virus (PRV) is a highly pathogenic agent that adversely impacts swine populations, leading to considerable economic losses within the Chinese pig industry. Furthermore, the potential for PRV to transmit across species from pigs to other hosts has attracted significant attention. In light of this, the identification of effective antiviral agents against PRV infection is of paramount importance. In this study, we investigated the antiviral properties of Diltiazem HCl (DTZ) against PRV infection in susceptible cell lines. Our results demonstrated that DTZ significantly inhibited PRV infection in both PK15 and Vero cells. Moreover, this chemical compound exhibited antiviral activity against both variant and classical strains of PRV, as well as herpes simplex virus type 1 (HSV-1). Time-of-addition assays showed that DTZ exerted its inhibitory effect through specific interference with the virus replication process. Subsequent transcriptomic analysis via RNA sequencing indicated that the calcium signaling pathway might be involved in the antiviral properties of DTZ against PRV infection. Specifically, treatment with EGTA or calcium ion (Ca2+)-free medium inhibited PRV infection; this inhibitory effect was substantially mitigated upon the reintroduction of CaCl2. In summary, DTZ effectively suppressed PRV infection in vitro, demonstrating its potential as an antiviral agent against PRV infections.