Peptidomimetic Oligomers Targeting Membrane Phosphatidylserine Exhibit Broad Antiviral Activity.

The development of durable new antiviral therapies is challenging, as viruses can evolve rapidly to establish resistance and attenuate therapeutic efficacy. New compounds that selectively target conserved viral features are attractive therapeutic candidates, particularly for combating newly emergent viral threats. The innate immune system features a sustained capability to combat pathogens through production of antimicrobial peptides (AMPs); however, these AMPs have shortcomings that can preclude clinical use.

Ribavirin Induces Polyamine Depletion via Nucleotide Depletion to Limit Virus Replication.

Common antivirals include nucleoside or nucleotide analogs with base prodrugs. The antiviral ribavirin, a US Food and Drug Administration (FDA)-approved nucleoside antimetabolite, halts guanine production, mutagenizes viral genomes, and activates interferon signaling. Here, we find that ribavirin induces spermidine-spermine N1-acetyltransferase (SAT1), a polyamine catabolic enzyme.

Polyamine Depletion Abrogates Enterovirus Cellular Attachment.

Polyamines are small polycationic molecules with flexible carbon chains that are found in all eukaryotic cells. Polyamines are involved in the regulation of many host processes and have been shown to be implicated in viral replication. Depletion of polyamine pools in cells treated with FDA-approved drugs restricts replication of diverse RNA viruses.

Coxsackievirus B3 Responds to Polyamine Depletion via Enhancement of 2A and 3C Protease Activity.

Polyamines are small positively-charged molecules abundant in eukaryotic cells that are crucial to RNA virus replication. In eukaryotic cells, polyamines facilitate processes such as transcription, translation, and DNA replication, and viruses similarly rely on polyamines to facilitate transcription and translation. Whether polyamines function at additional stages in viral replication remains poorly understood.

Polyamine Depletion Inhibits Bunyavirus Infection via Generation of Noninfectious Interfering Virions.

Several host and viral processes contribute to forming infectious virions. Polyamines are small host molecules that play diverse roles in viral replication. We previously demonstrated that polyamines are crucial for RNA viruses; however, the mechanisms by which polyamines function remain unknown.

DNA-binding studies of the natural β-carboline eudistomin U.

Eudistomin U is a member of the β-carboline class of heterocyclic amine-containing molecules that are capable of binding to DNA. The structure of eudistomin U is unique since it contains an indole ring at the 1-position of the pyridine ring. While simple β-carbolines are reported to intercalate DNA, an examination of the mode of binding of eudistomin U has been lacking.