Related Experiment Video
Updated: Aug 18, 2025
Cystic Fibrosis Aggregate Biofilm Model to Study Infection-relevant Gene Expression
Published on: April 18, 2025
Inhibitory activities of alginate phosphate and sulfate derivatives against SARS-CoV-2 in vitro
Cheng Yang1, Dan Li1, Shixin Wang2
1Key Laboratory of Marine Drugs of Ministry of Education, Shandong Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
Abstract:
Alginate derivatives have been demonstrated remarkable antiviral activities. Here we firstly identified polymannuronate phosphate (PMP) as a highly potential anti-SARS-CoV-2 agent. The structure-activity relationship showed polymannuronate monophosphate (PMPD, Mw: 5.8 kDa, P%: 8.7 %) was the most effective component to block the interaction of spike to ACE2 with an IC50 of 85.5 nM. Surface plasmon resonance study indicated that PMPD could bind to spike receptor binding domain (RBD) with the KD value of 78.59 nM. Molecular docking further suggested that the probable binding site of PMPD to spike RBD protein is the interaction interface between spike and ACE2. PMPD has the potential to inhibit the SARS-CoV-2 infection in an independent manner of heparan sulfate proteoglycans. In addition, polyguluronate sulfate (PGS) and propylene glycol alginate sodium sulfate (PSS) unexpectedly showed 3CLpro inhibition with an IC50 of 1.20 μM and 1.42 μM respectively. The polyguluronate backbone and sulfate group played pivotal roles in the 3CLpro inhibition. Overall, this study revealed the potential of PMPD as a novel agent against SARS-CoV-2. It also provided a theoretical basis for further study on the role of PGS and PSS as 3CLpro inhibitors.
Insights
Polymannuronate phosphate (PMP) derivatives show potent antiviral activity against SARS-CoV-2 by blocking spike-ACE2 interaction. Other alginates also inhibit 3CLpro, offering new therapeutic strategies.
Area of Science:
- Biochemistry
- Virology
- Drug Discovery
Background:
- Alginate derivatives possess demonstrated antiviral properties.
- SARS-CoV-2 infection relies on the spike protein binding to the ACE2 receptor.
- Identifying novel inhibitors is crucial for combating viral infections.
Purpose of the Study:
- To identify potent anti-SARS-CoV-2 agents from alginate derivatives.
- To elucidate the mechanism of action for inhibiting viral entry and replication.
- To explore the potential of alginates as therapeutic agents against SARS-CoV-2.
Main Methods:
- Structure-activity relationship analysis of polymannuronate phosphate (PMP) derivatives.
- Surface Plasmon Resonance (SPR) to determine binding kinetics.
- Molecular docking simulations to predict binding sites.
- Enzyme inhibition assays for 3CLpro activity.
Main Results:
- Polymannuronate monophosphate (PMPD) effectively blocked spike-ACE2 interaction (IC50: 85.5 nM) and bound to the spike RBD (KD: 78.59 nM).
- PMPD inhibits SARS-CoV-2 independently of heparan sulfate proteoglycans.
- Polyguluronate sulfate (PGS) and propylene glycol alginate sodium sulfate (PSS) inhibited 3CLpro (IC50: 1.20 μM and 1.42 μM, respectively).
Conclusions:
- PMPD is a promising novel agent for inhibiting SARS-CoV-2 entry.
- The study provides a theoretical basis for developing PGS and PSS as 3CLpro inhibitors.
- Alginate derivatives offer versatile strategies for antiviral drug development.
