RESUMO
Porcine epidemic diarrhea virus (PEDV) belongs to the genus Alphacoronavirus of the family Coronaviridae that causes severe diarrhea and high mortality in neonatal suckling piglets. Currently, there is no effective medication against this pathogen. Cepharanthine (CEP), tetrandrine (TET), and fangchinoline (FAN) are natural bis-benzylisoquinoline alkaloids with anti-inflammatory, antitumor, and antiviral properties. Here, we first found that CEP, TET, and FAN had anti-PEDV activity with IC50 values of 2.53, 3.50, and 6.69 µM, respectively. The compounds could block all the processes of viral cycles, but early application of the compounds before or during virus infection was advantageous over application at a late stage of virus replication. FAN performed inhibitory function more efficiently through interfering with the virus entry and attachment processes or through attenuating the virus directly. CEP had a more notable effect on virus entry. With the highest SI index of 11.8 among the three compounds, CEP was chosen to carry out animal experiments. CEP in a safe dosage of 11.1 mg/kg of body weight could reduce viral load and pathological change of piglet intestinal tracts caused by PEDV field strain challenge, indicating that CEP efficiently inhibited PEDV infection in vivo. All of these results demonstrated that the compounds of bis-benzylisoquinoline alkaloids could inhibit PEDV proliferation efficiently and had the potential of being developed for PED prevention and treatment.
Assuntos
Benzilisoquinolinas , Infecções por Coronavirus , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Animais , Benzilisoquinolinas/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/patologia , Infecções por Coronavirus/veterinária , Diarreia , Suínos , Doenças dos Suínos/patologiaRESUMO
BACKGROUND: Swine hepatitis E virus (swHEV) is a zoonotic disease that is considered a major problem in pig production and presents a threat to human health. Elucidation of the major antigenic epitopes of swHEV is essential for the effective control of swHEV epidemics. RESULTS: By bioinformatic analysis, we identified and then synthesized 12 peptides from open reading frames (ORFs) ORF1, ORF2 and ORF3, including swHEV-1 - swHEV-12. Using the results from ELISA, we selected swHEV-11 as the best candidate antigen and used it as a coating antigen for the development of peptide-based swine anti-HEV ELISA kits. The coefficient of variation (CV) the coefficient of variation (CV) varied between 4.3-7.2% in the same batch, and between 8.2-17.7% in six different batches. When comparing our swine peptide-based kit with the commercial recombinant-based kit, the humane anti-HEV IgG test had a 73.4% correspondence rate for them. CONCLUSION: This is the first systemic study to screen the diagnostic peptides of swHEV and our findings strongly suggest that peptide swHEV-11 is a potent diagnostic reagent of swHEV that could be used in the development of highly efficient diagnostic assays for the specific and highly sensitive detection of anti-HEV activity in swine serum samples.