Antifungal triazole posaconazole targets an early stage of the parechovirus A3 life cycle.
Antifungal triazole posaconazole targets an early stage of the parechovirus A3 life cycle.
Antimicrob Agents Chemother. 2019 Dec 09;:
Authors: Rhoden E, Ng TFF, Campagnoli R, Nix WA, Konopka-Anstadt J, Selvarangan R, Briesach L, Oberste MS, Weldon WC
Abstract
Viruses in species Parechovirus A (Picornaviridae) are associated with a wide variety of clinical manifestations. Parechovirus A3 (PeV-A3) is known to cause sepsis-like illness, meningitis, and encephalitis in infants and young children. To date, no specific therapies are available to treat PeV-A3-infected children. We had previously identified two FDA-cleared antifungal drugs, itraconazole (ITC) and posaconazole (POS) with potent and specific antiviral activity against PeV-A3. Time-of-addition and synchronized infection assays revealed that POS targets an early stage of the PeV-A3 life cycle. POS exerts an antiviral effect, evidenced by a reduction in viral titer following the addition of POS to Vero-P cells before infection, coaddition of POS and PeV-A3 to Vero-P cells, incubation of POS and PeV-A3 prior to Vero-P infection, and at attachment. POS exerts less of an effect on virus entry. A PeV-A3 ELISA inhibition experiment, using an anti-PeV-A3 monoclonal antibody (mAb), suggested that POS binds directly to the PeV-A3 capsid. POS-resistant PeV-A3 strains developed by serial passage in the presence of POS, acquired substitutions in multiple regions of the genome, including the...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Rhoden E, Ng TFF, Campagnoli R, Nix WA, Konopka-Anstadt J, Selvarangan R, Briesach L, Oberste MS, Weldon WC Tags: Antimicrob Agents Chemother Source Type: research
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