High-Sulfated Glycosaminoglycans Prevent Coronavirus Replication

Area of Science:

• Virology
• Biochemistry
• Drug Discovery

Background:

• Coronaviruses (CoVs) cause significant respiratory and gastrointestinal diseases in humans and animals.
• Limited antiviral drug options exist for CoVs, highlighting the urgent need for new treatments, especially for SARS-CoV-2.
• High-sulfated glycosaminoglycans (GAGs) are explored for their potential therapeutic properties.

Purpose of the Study:

• To characterize the antiviral effects of two high-sulfated GAG derivatives, based on hyaluronan (HA) and chondroitin sulfate (CS), against SARS-CoV-2 and bovine coronaviruses (BCoV).
• To evaluate the efficacy of these GAG derivatives in inhibiting viral replication and infection phases.

Main Methods:

• Investigated high-sulfated hyaluronan (sHA3) and chondroitin sulfate (sCS3) against BCoV and SARS-CoV-2.
• Conducted yield assays, time of addition assays, and attachment analyses.
• Utilized quantitative real-time RT PCR to assess viral load and inhibitor potency.

Main Results:

• Both sHA3 and sCS3 demonstrated strong inhibitory effects against BCoV and SARS-CoV-2 (B.1-lineage, Alpha, Beta).
• sHA3 showed significant inhibition of viral growth early in infection and even after virus absorbance.
• sHA3 and sCS3 inactivated BCoV through stable binding, without blocking virus attachment.

Conclusions:

• High-sulfated GAG derivatives (sHA3 and sCS3) exhibit potent antiviral activity against Betacoronaviruses.
• These compounds demonstrate low cytotoxicity and are promising candidates for novel anti-coronavirus therapies.
• Further development of these GAG derivatives could lead to effective treatments for COVID-19 and other CoV infections.