ABSTRACT
Porcine epidemic diarrhea virus (PEDV) has caused severe damage to the global pig industry in the past 20 years, creating an urgent demand for the development of associated medications. Flavonoids have emerged as promising candidates for combating coronaviruses. It is believed that certain flavonoids can directly inhibit the 3C-like protease (3CLpro), thus displaying antiviral activity against coronaviruses. In this investigation, we applied a flavonoid library to screen for natural compounds against PEDV 3CLpro. Baicalein and baicalin were found to efficiently inhibit PEDV 3CLproin vitro, with the IC50 value of 9.50 ± 1.02 µM and 65.80 ± 6.57 µM, respectively. A docking analysis supported that baicalein and baicalin might bind to the active site and binding pocket of PEDV 3CLpro. Moreover, both baicalein and baicalin successfully suppressed PEDV replication in Vero and LLC-PK1 cells, as indicated by reductions in viral RNA, protein, and titer. Further investigation revealed that baicalein and baicalin mainly inhibited the early viral replication of the post-entry stage. Furthermore, baicalein showed potential effects on the attachment or invasion step of PEDV. Collectively, our findings provide experimental proof for the inhibitory effects of baicalein and baicalin on PEDV 3CLpro activity and PEDV infection. These discoveries may introduce novel therapeutic strategies for controlling porcine epidemic diarrhea (PED).
ABSTRACT
Porcine epidemic diarrhea virus (PEDV) has become a challenging problem in pig industry all over the world, causing significant profit losses. Tannins and organic zinc have been shown to exert protective effects on the intestinal dysfunction caused by endotoxins. However, there is little information on tannic acid-chelated zinc (TAZ) supplementation in the diet of newborn piglets. This study was conducted to determine the effects of TAZ on the intestinal function of piglets infected with PEDV. Thirty-two 7-day-old piglets were randomly allocated to 1 of 4 treatments in a 2 × 2 factorial design consisting of 2 diets (0 or 50 mg/kg BW TAZ) and challenge (saline or PEDV). On day 9 of the trial, 8 pigs per treatment received either sterile saline or PEDV solution at 106 TCID50 (50% tissue culture infectious dose) per pig. Pigs infected with PEDV had greater diarrhea rate and lower average daily gain (ADG) (P < 0.05). PEDV infection decreased plasma D-xylose concentration, most antioxidative enzyme activities in plasma and intestine, as well as the small intestinal villus height (P < 0.05). Plasma diamine oxidase and blood parameters were also affected by PEDV infection. Dietary supplementation with TAZ could ameliorate the PEDV-induced changes in all measured variables (P < 0.05). Moreover, TAZ decreased the concentration of malondialdehyde in plasma, duodenum, jejunum, and colon (P < 0.05). Collectively, our results indicated that dietary TAZ could alleviate PEDV induced damage on intestinal mucosa and antioxidative capacity, and improve the absorptive function and growth in piglets. Therefore, our novel findings also suggest that TAZ, as a new feed additive for neonatal and weaning piglets, has the potential to be an alternative to ZnO.
