Research on natural products containing hexahydropyrrolo[2,3-b]indole (HPI) has dramatically increased during the past few years. Newly discovered natural products with complex structures and important biological activities have recently been isolated and synthesized. This review summarizes the structures, biological activities, and synthetic routes for natural compounds containing HPI, emphasizing the different strategies for assembling this motif. It covers a broad range of molecules, from small alkaloids to complex peptides.

The release of azidothymidine from macromolecular prodrugs was designed to respond to the intracellular disulfide reshuffling. This drug has no thiol groups, and a response to this trigger was engineered using a self-immolative linker. The resulting formulations were fast-acting, efficacious, and highly potent with regards to suppressing the infectivity of the virus.

Macromolecular ( pro)drugs are a sub-discipline of medicinal and polymer chemistries aiming to optimize the delivery of drugs to their site of action. In recent decades, this field of science has undergone a tremendous development, with the soundest achievements registered in the delivery of anticancer drugs.Surprisingly, the development of these tools for applications in antiviral treatment lags significantly behind despite the fact that the first in vivo successes of polymers in fighting viruses were reported half a century ago. Furthermore, the unique scope and utility of polymers in antiviral research is that macromolecules themselves exhibit highly potent activity against diverse viruses. Herein, in an attempt to revive the research interest in this field, we aim to provide an overview of successes (and failures) of polymers as antiviral agents and macromolecular prodrugs. Specifically, we discuss inhibition of the entry of the virus into mammalian cells by polymers, give an overview of the synthetic schemes applied for the conjugation of drugs to carrier polymers, and also present guidance with regard to potential reporter systems which can be used for the characterization of novel drug delivery systems in virus-free cell cultures.

Efficacious, potent, and at the same time nontoxic macromolecular prodrugs of ribavirin are designed taking advantage over prodrug activation by the intracellular milieu. Activity of these prodrugs is illustrated in the cells hosting hepatitis C virus replication and also in the cells implicated in the inflammatory response to the viral infection.