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: Tags: STKE Research Articles Source Type: news

Related Links:

CONCLUSIONS: ENP tissues have lower ACE2 expression than NENP; however, viral stimulation promotes ACE2/TMPRSS2 upregulation in ENP.PMID:34282808 | DOI:10.4193/Rhin21.001
Source: Rhinology - Category: ENT & OMF Authors: Source Type: research
Sci Signal. 2021 Jul 6;14(690):eabe5040. doi: 10.1126/scisignal.abe5040.ABSTRACTInorganic 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 ...
Source: Science Signaling - Category: Biomedical Science Authors: Source Type: research
CONCLUSION: Inflammatory endotype affects ACE2 expression in the nasal mucosa and influences susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In particular, type 2 inflammation could downregulate ACE2 expression in the nasal mucosa and reduces susceptibility to SARS-CoV-2 in patients with CRSwNP. Although in vivo experiments are required, administration of SCFAs to the nasal cavity might be worthy of consideration as a preventative or therapeutic strategy for the early-stage COVID-19.PMID:34232770 | DOI:10.1177/19458924211027798
Source: American Journal of Rhinology and Allergy - Category: ENT & OMF Authors: Source Type: research
Sci Signal. 2021 Jul 6;14(690):eabe5040. doi: 10.1126/scisignal.abe5040.ABSTRACTInorganic 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 ...
Source: Science Signaling - Category: Biomedical Science Authors: Source Type: research
Expert Rev Respir Med. 2021 May 29. doi: 10.1080/17476348.2021.1937132. Online ahead of print.ABSTRACTINTRODUCTION: Severe asthma and chronic rhinosinusitis (CRS), with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP), are heterogeneous diseases characterized by different mechanistic pathways (endotypes) and variable clinical presentations (phenotypes).AREAS COVERED: This review provides the clinician with an overview of the prevalence and clinical impact of severe chronic upper and lower airways disease and suggests a novel therapeutic approach with biological agents with possible biomarkers. To select relevant lit...
Source: Expert Review of Respiratory Medicine - Category: Respiratory Medicine Authors: Source Type: research
More News: Coronavirus | COVID-19 | Environmental Health | Nanotechnology | Polyps | Respiratory Medicine | SARS | Science | UK Health