Greetings. Several authors have identified in the past what seems to be a bacteriophage-derived antivirus against certain eukaryotic viruses, although no recent literature seem to cover similar findings.
The misterious compound was found present in phage solutions and was named "phagicin". Such molecule achieved antiviral effect against herpes simplex and vaccinia viruses through (what is seems to be) interference in the pathogens DNA replication (Article Differential Inhibition by Phagicin of DNA Synthesis in Cell...
;Article A Therapeutic Antiviral from an Extract of A Infected E. col...
).IFN induction by the phage genetic material was observed exercising an antiviral activity, being a possible explanation for antiviral activity in phage solutions. However, the compound "phagicin" was not disrupted by deoxyribonuclease, ribonuclease and ultraviolet irradiation, but it was sensitive to proteolytic enzymes, thus implying that the antiviral in question might be a bacteriophage protein Article A Therapeutic Antiviral from an Extract of A Infected E. col...
.Although such findings are exhilarating, no similar studies of an antiviral phage protein appears to be found in recent literature. Since many of the original authors are now deceased, I whould like to ask if there are any studies of protein-based bacteriophages antivirals being currently discussed, along with opinions about the nature of "phagicin".
Such insights whould be deeply appreciated. Thank you for your attention.
I can think of no biological mechanism whereby a phage protein would effectively inhibit a eukaryotic virus with notable efficacy. I have not read the papers but my guess is that there is some artifact from the bacterial cell lysis debris, or perhaps some released proteases, that is causing this effect.
Thank you Dr. Michael J. Benedik . Indeed, there are few articles covering protein-based antivirals from bacteriophage molecules. The only recent phage-protein-antiviral that I could find was the blocking of Influenza A spike proteins by phage aggregates, essentially covering the influenza structure in a phage-protein net and blocking the virus binding sites, being such interaction confirmed by electron microscopy (10.1038/s41565-020-0660-2). However the studies covering “phagicin” cite this protein as having an intracellular effect, interfering in the eukaryotic viruses DNA synthesis. “Phagicin” mechanism appears to possess an effect much similar to bacterial phage-like injection systems, in which the structure (likely derived from prophages) inject reactive proteins which disrupt the intracellular environment, being able to affect even eukaryotic cells (10.1038/s41564-019-0530-6 ; 10.1016/j.celrep.2019.06.019).
In relation with proteases and cell debris contamination I don’t think this could be the issue since the authors claim to have purified the samples from bacterial debris before usage (although I agree that it may not be possible to be fully sure of the sample purity, being bacterial proteases a likely explanation if true), which makes me wonder if the “phagicin” possess a similar mechanism observed in phage-like injection systems or acts by a different method (if phagicin really exists). My question is not exactly how such antiviral acts, but more specifically if such a compound even exists and what other phage protein could induce a similar effect observed in the studies.
I eagerly await further insights.
I am not aware of anything that has been well studied and demonstrated to act in the manner you indicate. I think there are likely a number of unusual one-off cases in the literature such as the phage aggregation mechanism you described, undoubtedly not evolved to have the effect of inhibiting another virus but just an accidental byproduct of aggregation.
While you do have bacterial injection systems that can translocate toxins into eukaryotic cells, these are also highly specific. I haven't kept up with that literature recently but I don't think they have any relationship to phages but are closely related to some secretion systems. A few filamentous phages have aspects that are in common. But if you think about a phage, the only thing it injects is its nucleic acid (and in some cases a few molecules of a few proteins. So not likely to be active against other viruses, certainly not extracellularly.
Now if you wanted to be really cute you might design an antiviral aptamer and use a phage system for high level production. But you might need to strip it from the coat proteins for efficacy. I doubt this has evolved in nature because I can think of no positive selection whereby this would be advantageous to the phage and evolve.
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