Identification of porcine reproductive and respiratory syndrome virus inhibitors through an oriented screening on natural products

Abstract

Porcine reproductive and respiratory syndrome(PRRS) caused by porcine reproductive and respiratory syndrome virus(PRRSV) is one of the most infectious diseases in the swine industry worldwide, causing big economic losses. Vaccines are major weapons against PRRSV, however, current available vaccines have several limitations. Developing chemical drugs as alternatives is required. On the basis of traditional medical knowledge, we purposely selected 15 natural products originated from Chinese herbs with anti-infectious effects. Their antiviral activities were evaluated by PRRSV-induced cytopathic effect(CPE) on MARC-145 cells and reverse transcription polymerase chain reaction(RT-PCR) assay. Compounds ethoxysanguinarine(EOSG) and atractylodinol were found to be the hits which could significantly reduce PRRSV-associated CPE with 50% inhibited concentration(IC₅₀) values of 7.9 and 39.4 μmol/L, respectively. Meanwhile, compounds ethoxysanguinarine and atractylodinol significantly decreased mRNA expression of ORF7 gene in a dose-dependent manner. Study results suggest that compounds ethoxysanguinarine and atractylodinol may be useful anti-PRRSV drugs for swine industry or the hits for further lead optimization.

Keywords

Porcine reproductive and respiratory syndrome virus(PRRSV) / Natural product / Cytopathic effect / Antiviral activity

References

[1] GorbalenyaA. E., EnjuanesL., ZiebuhrJ., SnijderE. J.Virus Res., 2006, 117117.

[2] PolsonD. D., MarshW. E., DialG. D.North. Am. Food Anim. Pract., 1992, 83725

[3] DeeS. A., JooH. S., PolsonD. D., MarshW. E.Vet. Rec., 1997, 14019498.

[4] MengelingW. L., LagerK. M., VorwaldA. C.Am. J. Vet. Res., 1998, 59121540

[5] MeulenbergJ. J.Vet. Res., 2000, 31111

[6] YaegerM. J., PrieveT., CollinsJ., Christopher-HenningsJ., NelsonE., BenfieldD.J. Swine Health Prod., 1993, 157

[7] WillsR. W., ZimmermanJ. J., YoonK. J., SwensonS. L., HoffmanL. J., McGinleyM. J., HillH. T., PlattK. B.Vet. Microbiol., 1997, 57169.

[8] TorremorellM., PijoanC., JanniK., WalkerR., JooH. S.J. Vet. Res., 1997, 588828

[9] HuangY. W., MengX. J.Virus Res., 2010, 1541/2141.

[10] ThanawongnuwechR., SuradhatS.Virus Res., 2010, 1541/2133.

[11] SmithR. D.Soc. Sci. Med., 2006, 63123113.

[12] NewmanD. J., CraggG. M., SnaderK. M.J. Nat. Prod., 2003, 6671022.

[13] DuanB. F., ShenY. P., YangG. S., ZhangY. F., WuJ. M., DuanG., YinG. F.Prog. Vet. Med., 2010, 31: 11

[14] TantularI. S., KawamotoF.Trop. Med. Int. Health, 2003, 86569.

[15] MaS. C., HeZ. D., DengX. L., ButP. P., OoiV. E., XuH. X., LeeS. H., LeeS. F.Chem. Pharm. Bull.(Tokyo), 2001, 49111471.

[16] PfafflM. W.Nucleic Acids Res., 2001, 299e45.

[17] KinghornA. D., PanL., FletcherJ. N., ChaiH.J. Nat. Prod., 2011, 7461539.

[18] Fabricant D. S., Farnsworth N. R., The Environ. Health Perspect., 2001, Suppl.1, 69

[19] XueX., ZhangH. F., BaiX. H., YueY.Chem. J. Chinese Universities, 2012, 335942

[20] ZongM. R., ZhaoY. H., ZhangK., YangL. F., ZhengY. C., HeC. Y.Chem. Res. Chinese Universities, 2011, 272241

[21] KosinaP., WalterovaD., UlrichovaJ., LichnovskyV., StiborovaM., RydlovaH., VicarJ., KrecmanV., BrabecM. J., SimanekV.Food Chem. Toxicol., 2004, 42185.

[22] LuoG. F., XiaoS. J.Vet. Pharmaceut & Feed Addit., 2009, 14522

[23] BasiniG., SantiniS. E., BussolatiS., GrasselliF.J. Reprod. Dev., 2007, 533573.

[24] ChanW. H.Toxicol. Lett., 2011, 2053285.

RIGHTS & PERMISSIONS

Jilin University, The Editorial Department of Chemical Research in Chinese Universities and Springer-Verlag GmbH