Long-chain polyphosphates impair SARS-CoV-2 infection and replication
Inorganic polyphosphates (polyPs) are linear polymers composed of repeated phosphate (PO43–) 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.
Source: Signal Transduction Knowledge Environment - Category: Science Authors: Ferrucci, V., Kong, D.-Y., Asadzadeh, F., Marrone, L., Boccia, A., Siciliano, R., Criscuolo, G., Anastasio, C., Quarantelli, F., Comegna, M., Pisano, I., Passariello, M., Iacobucci, I., Monica, R. D., Izzo, B., Cerino, P., Fusco, G., Viscardi, M., Brandi, Tags: STKE Research Articles Source Type: news
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