Antiviral Agents From Fungi: Diversity, Mechanisms and Potential Applications

Abstract

Viral infections are amongst the most common diseases affecting people worldwide. New viruses emerge all the time and presently we have limited number of vaccines and only few antivirals to combat viral diseases. Fungi represent a vast source of bioactive molecules, which could potentially be used as antivirals in the future. Here, we have summarized the current knowledge of fungi as producers of antiviral compounds and discuss their potential applications. In particular, we have investigated how the antiviral action has been assessed and what is known about the molecular mechanisms and actual targets. Furthermore, we highlight the importance of accurate fungal species identification on antiviral and other natural products studies.

Keywords: antiviral agents; antiviral mechanisms; endophytes; fungal secondary metabolites; medicinal mushrooms; natural products.

FIGURE 1

A tree illustrating the larger phylogeny of Fungi shows that the origin of presently known fungal-derived antiviral agents (highlighted) is restricted to the late-diverging fungal phyla (Ascomycota and Basidiomycota). The figure is constructed based on phylogenetic relationships of Fungi on Tree of Life Web Project (http://tolweb.org). This tree is illustrative and does not represent real phylogenetic data. Dashed lines: The group may not be monophyletic, or phylogenetic position of the group is uncertain.

FIGURE 2

In phylum Ascomycota, antiviral agents have been mainly identified from endophytes and other microfungi restricted to limited number of orders. Higher red color intensity indicates higher number of reports in literature. The figure is constructed based on phylogenetic relationships of Fungi on Tree of Life Web Project (http://tolweb.org). This tree is illustrative and does not represent real phylogenetic data. IA, indole alkaloids; NRPS, non-ribosomal peptides; PKS, polyketides; NRPS-PKS, hybrids; T, terpenoids; N/A, information not available. Dashed lines: The group may not be monophyletic, or phylogenetic position of the group is uncertain.

FIGURE 3

Antiviral agents reported from the phylum Basidiomycota. Higher red color intensity indicates higher number of reports in literature. The figure is constructed based on phylogenetic relationships of Fungi on Tree of Life Web Project (http://tolweb.org). This tree is illustrative and does not represent real phylogenetic data. L, lignin derivative; PS, polysaccharides; P, proteins; C, polysaccharide-protein/amino acid complex; NRPS, non-ribosomal peptides; PKS, polyketides; T, terpenoids; N/A, information not available. Dashed lines: The group may not be monophyletic, or phylogenetic position of the group is uncertain.

FIGURE 4

A schematic representation of the life-cycle of a non-enveloped, positive sense single-stranded RNA. The infection stages of the virus that include attachment, entry, uncoating, genome release, genomic replication, translation, assembly and exit serve as potential targets for antivirals.