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Viral endoribonuclease plays a vital role in the physiological and biochemical activities of viral RNA.In our studies on PRRSV,we seek to screen candidate antiviral molecules that target this endoribonuclease.Through 5 rounds of phage-display screening of 12-ammino acid peptides,4 peptides that show high affinity to the viral endoribonuclease were identified.In vitro experiments showed very high antiviral activity of all these 4 peptides.Wherein,the E4 peptide(NIPIKPRPRLMK)showed the highest antiviral activity(IC50 = 39.21μM),yet the lowest cytotoxicity.E4 can directly bind to the endoribonuclease of PRRSV(NSP11)and reduce copy number of viral RNA by 23.68 folds.Through large-scale phage-display screening and following in vitro analysis,we proved that viral endoribonuclease is a potential target of antiviral drugs.