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F1000Res . Evidence of SARS-CoV-2 bacteriophage potential in human gut microbiota

tetano

Editor, Senior Moderator
F1000Res


. 2025 Apr 23:11:292.
doi: 10.12688/f1000research.109236.2. eCollection 2022. Evidence of SARS-CoV-2 bacteriophage potential in human gut microbiota

Mauro Petrillo[SUP] #[/SUP][SUP] 1 [/SUP], Maddalena Querci[SUP] #[/SUP][SUP] 2 [/SUP], Carlo Brogna[SUP] #[/SUP][SUP] 3 [/SUP], Jessica Ponti[SUP] #[/SUP][SUP] 2 [/SUP], Simone Cristoni[SUP] #[/SUP][SUP] 4 [/SUP], Peter V Markov[SUP] 2 [/SUP], Andrea Valsesia[SUP] 2 [/SUP], Gabriele Leoni[SUP] 2 5 [/SUP], Alessandro Benedetti[SUP] 6 [/SUP], Thierry Wiss[SUP] 6 [/SUP], Guy Van den Eede[SUP] 7 [/SUP]



Affiliations
Abstract

Background: In previous studies we have shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates in vitro in bacterial growth medium, that the viral replication follows bacterial growth, and it is influenced by the administration of specific antibiotics. These observations are compatible with a 'bacteriophage-like' behaviour of SARS-CoV-2.
Methods: We have further elaborated on these unusual findings and here we present the results of three different supplementary experiments: (1) an electron-microscope analysis of samples of bacteria obtained from a faecal sample of a subject positive to SARS-CoV-2; (2) mass spectrometric analysis of these cultures to assess the eventual de novo synthesis of SARS-CoV-2 spike protein; (3) sequencing of SARS-CoV-2 collected from plaques obtained from two different gut microbial bacteria inoculated with supernatant from faecal microbiota of an individual positive to SARS-CoV-2.
Results: Immuno-labelling with Anti-SARS-CoV-2 nucleocapsid protein antibody confirmed presence of SARS-CoV-2 both outside and inside bacteria. De novo synthesis of SARS-CoV-2 spike protein was observed, as evidence that SARS-CoV-2 RNA is translated in the bacterial cultures. In addition, phage-like plaques were spotted on faecal bacteria cultures after inoculation with supernatant from faecal microbiota of an individual positive to SARS-CoV-2. Bioinformatic analyses on the reads obtained by sequencing RNA extracted from the plaques revealed nucleic acid polymorphisms, suggesting different replication environment in the two bacterial cultures.
Conclusions: Based on these results we conclude that, in addition to its well-documented interactions with eukaryotic cells, SARS-CoV-2 may act as a bacteriophage when interacting with at least two bacterial species known to be present in the human microbiota. If the hypothesis proposed, i.e., that under certain conditions SARS-CoV-2 may multiply at the expense of human gut bacteria, is further substantiated, it would drastically change the model of acting and infecting of SARS-CoV-2, and most likely that of other human pathogenic viruses.

Keywords: COVID-19; SARS-CoV-2; gut microbiota.

 
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