The Effect of Matrine and Glycyrrhizic Acid on Porcine Reproductive and Respiratory Syndrome Virus in vitro and in vivo

Abstract

Abstract Porcine reproductive and respiratory syndrome is endemic worldwide, seriously affecting development of the pig industry, but vaccine strategies have limited protective effects against PRRSV transmission. The aim of this study was to identify potential anti-PRRSV drugs. We examined the cytotoxicity of seven compounds formulated by the mass ratio between glycyrrhizic acid and matrine and their inhibition rate against PRRSV in vitro. The results showed that the seven compounds all had direct killing and therapeutic effects on PRRSV, and the compounds inhibited PRRSV replication in a time- and dose-dependent manner. Then, the compound with the best anti-PRRSV effect was selected for subsequent in vivo experiments. Pigs were divided into a control group and a medication group to conduct the in vivo evaluation. The results showed that pigs treated with the 4:1 compound had 100% morbidity after PRRSV challenge, and the mortality rate reached 75% on the 8th day of the challenge. These results suggest that this compound has no practical anti-PRRSV effect in vivo and can instead accelerate the death of infected pigs. Next, we further analyzed the semiprotective pigs obtained from the vaccine through the compound to determine whether the compound can synergize with the vaccine in vivo. The results indicated that pigs treated with the compound had higher mortality and more severe clinical reactions after PRRSV infection (p < 0.05). The levels of proinflammatory cytokines (IL-6, IL-8, IL-1β, IFN-γ, TNF-α) were significantly upregulated in the compound-treated pigs compared to the positive control group (p < 0.05), and there was no synergistic enhancement with the live attenuated PRRSV vaccine (p < 0.05). The compound enhanced the inflammatory response, prompted the body to produce excessive inflammatory cytokines and caused body damage, preventing the therapeutic effect from being produced. In conclusion, the present study revealed that effectiveness in vitro does not mean that it is effective in vivo in developing anti-PRRSV drugs. Our finding showed that, in order to find the effective anti-PRRSV drugs, comprehensive drug screening is required, at least with solid anti-inflammatory ability in vitro and in vivo. Our study may help the development of new anti-PRRSV drugs.