Susceptibility of widely diverse influenza a viruses to PB2 polymerase inhibitor pimodivir
Mira C. Patel, Anton Chesnokov, Joyce Jones, Vasiliy P. Mishin, Juan A. De La Cruz, Ha Nguyen, Natosha Zanders, David E. Wentworth, Todd Davis, Larisa V. Gubareva
Abstract
values determined by HINT were similar for both subtypes of seasonal viruses, A(H1N1)pdm09 and A(H3N2), across three seasons. Human seasonal viruses with PB2 substitutions S324C, S324R, or N510K displayed a 27-317-fold reduced pimodivir susceptibility by HINT. In addition, pimodivir was effective at inhibiting replication of a diverse group of animal-origin viruses that have pandemic potential, including avian viruses of A(H5N6) and A(H7N9) subtypes. A rare PB2 substitution H357N was identified in an A(H4N2) subtype poultry virus that displayed >100-fold reduced pimodivir susceptibility. Our findings demonstrate a broad inhibitory activity of pimodivir and expand the existing knowledge of amino acid substitutions that can reduce susceptibility to this investigational antiviral.