Merck

Long-chain polyphosphates impair SARS-CoV-2 infection and replication.

Science signaling (2021-07-08)
Veronica Ferrucci, Dae-Young Kong, Fatemeh Asadzadeh, Laura Marrone, Angelo Boccia, Roberto Siciliano, Giuseppina Criscuolo, Camilla Anastasio, Fabrizio Quarantelli, Marika Comegna, Ida Pisano, Margherita Passariello, Ilaria Iacobucci, Rosa Della Monica, Barbara Izzo, Pellegrino Cerino, Giovanna Fusco, Maurizio Viscardi, Sergio Brandi, Bianca Maria Pierri, Giorgia Borriello, Claudia Tiberio, Luigi Atripaldi, Martina Bianchi, Giovanni Paolella, Ettore Capoluongo, Giuseppe Castaldo, Lorenzo Chiariotti, Maria Monti, Claudia De Lorenzo, Kyong-Seop Yun, Stefano Pascarella, Jae-Ho Cheong, Hong-Yeoul Kim, Massimo Zollo
ABSTRACT

Inorganic polyphosphates (polyPs) are linear polymers composed of repeated phosphate (PO4 3-) units linked together by multiple high-energy phosphoanhydride bonds. In addition to being a source of energy, polyPs have cytoprotective and antiviral activities. Here, we investigated the antiviral activities of long-chain polyPs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In molecular docking analyses, polyPs interacted with several conserved amino acid residues in angiotensin-converting enzyme 2 (ACE2), the host receptor that facilitates virus entry, and in viral RNA-dependent RNA polymerase (RdRp). ELISA and limited proteolysis assays using nano- LC-MS/MS mapped polyP120 binding to ACE2, and site-directed mutagenesis confirmed interactions between ACE2 and SARS-CoV-2 RdRp and identified the specific amino acid residues involved. PolyP120 enhanced the proteasomal degradation of both ACE2 and RdRp, thus impairing replication of the British B.1.1.7 SARS-CoV-2 variant. We thus tested polyPs for functional interactions with the virus in SARS-CoV-2-infected Vero E6 and Caco2 cells and in primary human nasal epithelial cells. Delivery of a nebulized form of polyP120 reduced the amounts of viral positive-sense genomic and subgenomic RNAs, of RNA transcripts encoding proinflammatory cytokines, and of viral structural proteins, thereby presenting SARS-CoV-2 infection in cells in vitro.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
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