Enhanced Antiviral Function of Magnesium Chloride-Modified Heparin on a Broad Spectrum of Viruses

Abstract

Previous studies reported on the broad-spectrum antiviral function of heparin. Here we investigated the antiviral function of magnesium-modified heparin and found that modified heparin displayed a significantly enhanced antiviral function against human adenovirus (HAdV) in immortalized and primary cells. Nuclear magnetic resonance analyses revealed a conformational change of heparin when complexed with magnesium. To broadly explore this discovery, we tested the antiviral function of modified heparin against herpes simplex virus type 1 (HSV-1) and found that the replication of HSV-1 was even further decreased compared to aciclovir. Moreover, we investigated the antiviral effect against the new severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and measured a 55-fold decreased viral load in the supernatant of infected cells associated with a 38-fold decrease in virus growth. The advantage of our modified heparin is an increased antiviral effect compared to regular heparin.

Metal Binding to Sodium Heparin Monitored by Quadrupolar NMR

“…The ubiquitous presence of negatively charged proteoglycans in the extracellular space can act as buffers for positively charged metal and organic ions and thereby influence various physiological and pathophysiological processes outside the cells [ 12 , 13 ]. In addition, it is known that ions such as Ca 2+ or Mg 2+ can alter the conformation of heparin and consequently modulate their functions, e.g., in host defense against pathogens [ 10 ]. In neurodegenerative diseases, heparins are known to trigger pathogenic aggregation of proteins such as tau protein in a metal ion-dependent manner on the one hand [ 7 , 36 , 37 , 38 ] and act as neuroprotective agents on the other hand [ 9 ].…”

“…They play significant roles in many pathophysiological processes, such as cell-to-cell and cell-to-matrix signaling, inflammation, cellular growth and differentiation, angiogenesis, blood coagulation, and host defense against pathogens [ 5 , 7 , 8 ]. In recent years, the pharmacological application of heparin and heparin-like GAGs has extended from their classic use as anti-coagulant and anti-thrombotic agents to potential anti-inflammation, neuroprotective, antiviral, and anti-cancer therapeutics [ 1 , 9 , 10 ].…”

“…Heparins can serve as a reservoir of metal ions in the extracellular environment and regulate metal ion-dependent biomolecular activities [ 12 ]. In addition, the binding of heparin to metal ions can alter the three-dimensional structure of heparin, hence modulating its interaction with various biomolecular targets [ 10 , 12 , 13 ].…”

The diverse role of heparan sulfate and other GAGs in SARS-CoV-2 infections and therapeutics

“…In any event, there are general trends that have been observed regarding GAG-SARS-CoV-2 interactions as follows: SARS-CoV-2 binding to GAGs is the strongest for HS, including heparin, and can become stronger when complexed with metal ions. For example, Mg 2+ -complexed heparin had increased anti-SARS-CoV-2 activity compared to native heparin ( Mese et al, 2021 ). Furthermore, several GAGs like fucans and galactans showed high affinity binding to SARS-CoV-2 ( Tandon et al, 2021 ).…”

Sulfated Polysaccharides from Seaweed Strandings as Renewable Source for Potential Antivirals against Herpes simplex Virus 1

“…In our study, the antiviral activity at this step could be related to the presence of the small peak with a molecular weight estimated of 4.4 kDa, since low molecular weight compounds (LMWC) have shown activity at the intracellular level. The LMWC 3-O-sulfated octasaccharide obtained from heparin had strong activity in blocking HSV-1 infection [58], and the magnesium-modified heparin show a highly non-specific transduction inhibition on HSV-1 [59]. Further studies are required to understand the inhibition of viral infection by the carrageenan of Halymenia floresii.…”