Phage display library based antiviral screening: porcine respiratory and reproductive syndrome virus endoribonuclease is a target for antiviral screening

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. The E4 peptide (NIPIKPRPRLMK) showed the highest antiviral activity (IC50 = 39.21 mu M), 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 largescale phage-display screening and following in vitro analysis, we proved that viral endoribonuclease is a potential target of antiviral drugs.