Anti-SARS-CoV-2 Activity of Rhamnan Sulfate from Monostroma nitidum.

Yuefan Song,Fuming Zhang,Chen Chen,Robert J Linhardt,Michael A Bierdeman,Peng He,Jonathan Dordick,Payel Datta,Andre L Rodrigues,John T Bates,Ritesh Tandon

doi:10.3390/md19120685

Abstract

The COVID-19 pandemic is a major human health concern. The pathogen responsible for COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), invades its host through the interaction of its spike (S) protein with a host cell receptor, angiotensin-converting enzyme 2 (ACE2). In addition to ACE2, heparan sulfate (HS) on the surface of host cells also plays a significant role as a co-receptor. Our previous studies demonstrated that sulfated glycans, such as heparin and fucoidans, show anti-COVID-19 activities. In the current study, rhamnan sulfate (RS), a polysaccharide with a rhamnose backbone from a green seaweed, Monostroma nitidum, was evaluated for binding to the S-protein from SARS-CoV-2 and inhibition of viral infectivity in vitro. The structural characteristics of RS were investigated by determining its monosaccharide composition and performing two-dimensional nuclear magnetic resonance. RS inhibition of the interaction of heparin, a highly sulfated HS, with the SARS-CoV-2 spike protein (from wild type and different mutant variants) was studied using surface plasmon resonance (SPR). In competitive binding studies, the IC50 of RS against the S-protein receptor binding domain (RBD) binding to immobilized heparin was 1.6 ng/mL, which is much lower than the IC50 for heparin (~750 ng/mL). RS showed stronger inhibition than heparin on the S-protein RBD or pseudoviral particles binding to immobilized heparin. Finally, in an in vitro cell-based assay, RS showed strong antiviral activities against wild type SARS-CoV-2 and the delta variant.

Highlights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a single-stranded positive RNA virus bearing a membrane envelope, is the pathogen that causes COVID-19
We found that rhamnan sulfate (RS) from M. nitidum is as competitive as the fucoidans and iota-carrageenan in its potential to combat COVID-19 [26,28], which is reflected by its high capacity in binding the S-protein and neutralizing the pseudotyped virus in vitro
We explored the anti-SARS-CoV-2 activity of a RS fraction from the green algae M. nitidum

Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a single-stranded positive RNA virus bearing a membrane envelope, is the pathogen that causes COVID-19. The invasion of SARS-CoV-2 is achieved by the interaction of its spike protein (S-protein) with angiotensin-converting enzyme 2 (ACE2), which acts as the major receptor for the S-protein, leading to viral entry into susceptible cells In addition to this major receptor, there are co-receptors/cofactors that play significant roles in the invasion process [1]. SPR competition assays revealed that heparin has a higher binding preference for the SARS-CoV-2 S-protein than various desulfated heparin derivatives and other glycosaminoglycans (GAGs), indicating that the binding of GAGs to the S-protein is greatly influenced by their degree of sulfation [6] These data suggest that the sulfated glycans, including the natural products of a variety of organisms, may represent promising therapeutics for the prevention or treatment of COVID-19 infection

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