TY - JOUR TI - A polyomavirus peptide binds to the capsid VP1 pore and has potent antiviral activity against BK and JC polyomaviruses AU - Kane, Joshua R AU - Fong, Susan AU - Shaul, Jacob AU - Frommlet, Alexandra AU - Frank, Andreas O AU - Knapp, Mark AU - Bussiere, Dirksen E AU - Kim, Peter AU - Ornelas, Elizabeth AU - Cuellar, Carlos AU - Hyrina, Anastasia AU - Abend, Johanna R AU - Wartchow, Charles A A2 - Sundquist, Wesley I A2 - Wolberger, Cynthia A2 - DiMaio, Daniel VL - 9 PY - 2020 DA - 2020/01/21 SP - e50722 C1 - eLife 2020;9:e50722 DO - 10.7554/eLife.50722 UR - https://doi.org/10.7554/eLife.50722 AB - In pursuit of therapeutics for human polyomaviruses, we identified a peptide derived from the BK polyomavirus (BKV) minor structural proteins VP2/3 that is a potent inhibitor of BKV infection with no observable cellular toxicity. The thirteen-residue peptide binds to major structural protein VP1 with single-digit nanomolar affinity. Alanine-scanning of the peptide identified three key residues, substitution of each of which results in ~1000 fold loss of binding affinity with a concomitant reduction in antiviral activity. Structural studies demonstrate specific binding of the peptide to the pore of pentameric VP1. Cell-based assays demonstrate nanomolar inhibition (EC50) of BKV infection and suggest that the peptide acts early in the viral entry pathway. Homologous peptide exhibits similar binding to JC polyomavirus VP1 and inhibits infection with similar potency to BKV in a model cell line. Lastly, these studies validate targeting the VP1 pore as a novel strategy for the development of anti-polyomavirus agents. KW - BK polyomavirus KW - JC polyomavirus KW - peptide KW - antiviral JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -