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Long-chain polyphosphates impair SARS-CoV-2 infection and replication: a route for therapy in man

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Date: 18th November 2020 | Source: bioRxiv

Authors: Veronica Ferrucci, Dae-Young Kong, Fatemeh Asadzadeh, Laura Marrone, Roberto Siciliano, Pellegrino Cerino, Giuseppina Criscuolo, Ida Pisano, Fabrizio Quarantelli, Barbara Izzo, Giovanna Fusco, Marika Comegna, Angelo Boccia, Maurizio Viscardi, Giorgia Borriello, Sergio Brandi, Bianca Maria Pierri, Claudia Tiberio, Luigi Atripaldi, Giovanni Paolella, Giuseppe Castaldo, Stefano Pascarella, Martina Bianchi, Rosa Della Monica, Lorenzo Chiariotti, Kyong-Seop Yun, Jae-Ho Cheong, Hong-Yeoul Kim, Massimo Zollo.

Anti-viral activities of long-chain inorganic polyphosphates (PolyPs) against severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection were investigated. In molecular docking analyses, PolyPs interacted with several conserved angiotensin-converting enzyme (ACE)2 and RNA-dependent RNA polymerase (RdRp) amino acids.

We thus tested PolyPs for functional interactions in vitro in SARS-CoV-2–infected Vero E6, Caco2 and human primary nasal epithelial cells. Immunofluorescence, qPCR, direct RNA sequencing, FISH and Immunoblotting were used to determine virus loads and transcription levels of genomic(g)RNAs and sub-genomic(sg)RNAs.

We show that PolyP120 binds to ACE2 and enhances its proteasomal degradation. PolyP120 shows steric hindrance of the genomic Sars-CoV-2-RNA/RdRP complex, to impair synthesis of positive-sense gRNAs, viral subgenomic transcripts and structural proteins needed for viral replication. Thus, PolyP120 impairs infection and replication of Korean and European (containing non-synonymous variants) SARS-CoV-2 strains.

As PolyPs have no toxic activities, we envision their use as a nebulised formula for oropharyngeal delivery to prevent infections of SARS-CoV-2 and during early phases of antiviral therapy.

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