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1.
Carbohydrate Polymers ; : 119818, 2022.
Article in English | ScienceDirect | ID: covidwho-1914200

ABSTRACT

Heparin, an old but first-line anticoagulant, has been used over a century. It is a heterogeneous, linear, highly sulfated, anionic glycosaminoglycan with a broad distribution in relative molecular weight and charge density. These structural properties allow heparin to selectively interact with multiple proteins, leading to heparin's various pharmacological functions, such as anticoagulant, anti-viral, anti-tumor and anti-inflammatory activities. Clinical data suggest that unfractionated heparin or low molecule weight heparin could decrease mortality in COVID-19 patients with sepsis-induced hypercoagulation through the anticoagulant, anti-viral and anti-inflammatory activities of these drugs. Thus, the non-anticoagulant activity of heparin has again aroused attention. This review highlights recent advances in the preparation of heparin-derived drugs and clinical research on its non-anticoagulant properties over the past decade, to further the development and utilization of these important drugs.

2.
J Biol Chem ; 298(5): 101856, 2022 05.
Article in English | MEDLINE | ID: covidwho-1814630

ABSTRACT

Sulfation pattern and molecular weight (MW) play a key role in the biological actions of sulfated glycans. Besides anticoagulant effects, certain sulfated glycans can also exhibit anti-SARS-CoV-2 properties. To develop a more selective antiviral carbohydrate, an efficient strategy to separate these two actions is required. In this work, low MW fractions derived from the red alga Botryocladia occidentalis sulfated galactan (BoSG) were generated, structurally characterized, and tested for activity against SARS-CoV-2 and blood coagulation. The lowest MW fraction was found to be primarily composed of octasaccharides of monosulfated monosaccharides. Unlike heparin or native BoSG, we found that hydrolyzed BoSG products had weak anticoagulant activities as seen by aPTT and inhibitory assays using purified cofactors. In contrast, lower MW BoSG-derivatives retained anti-SARS-CoV-2 activity using SARS-CoV-2 spike (S)-protein pseudotyped lentivirus vector in HEK-293T-hACE2 cells monitored by GFP. Surface plasmon resonance confirmed that longer chains are necessary for BoSG to interact with coagulation cofactors but is not required for interactions with certain S-protein variants. We observed distinct affinities of BoSG derivatives for the S-proteins of different SARS-CoV-2 strains, including WT, N501Y (Alpha), K417T/E484K/N501Y (Gamma), and L542R (Delta) mutants, and stronger affinity for the N501Y-containing variants. Docking of the four possible monosulfated BoSG disaccharides in interactions with the N501Y mutant S-protein predicted potential binding poses of the BoSG constructs and favorable binding in close proximity to the 501Y residue. Our results demonstrate that depolymerization and fractionation of BoSG are an effective strategy to segregate its anticoagulant property from its anti-SARS-CoV-2 action.


Subject(s)
Anticoagulants , Antiviral Agents , Galactans , Rhodophyta , SARS-CoV-2 , Anticoagulants/chemistry , Anticoagulants/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , COVID-19 , Galactans/chemistry , Galactans/pharmacology , HEK293 Cells , Humans , Rhodophyta/chemistry , SARS-CoV-2/drug effects , Spike Glycoprotein, Coronavirus/chemistry , Sulfates/chemistry
3.
The Journal of biological chemistry ; 2022.
Article in English | EuropePMC | ID: covidwho-1755836

ABSTRACT

Sulfation pattern and molecular weight (MW) play a key role in the biological actions of sulfated glycans. Besides anticoagulant effects, certain sulfated glycans can also exhibit anti-SARS-CoV-2 properties. To develop a more selective antiviral carbohydrate, an efficient strategy to separate these two actions is required. In this work, low MW fractions derived from the red alga Botryocladia occidentalis sulfated galactan (BoSG) were generated, structurally characterized, and tested for activity against SARS-CoV-2 and blood coagulation. The lowest MW fraction was found to be primarily composed of octasaccharides of monosulfated monosaccharides. Unlike heparin or native BoSG, we found that hydrolyzed BoSG products had weak anticoagulant activities as seen by aPTT and inhibitory assays using purified co-factors. In contrast, lower MW BoSG-derivatives retained anti-SARS-CoV-2 activity using SARS-CoV-2 spike (S)-protein pseudotyped lentivirus vector in HEK293T cells monitored by green fluorescent protein. Surface plasmon resonance confirmed that longer chains are necessary for BoSG to interact with coagulation co-factors but is not required for interactions with certain S-protein variants. We observed distinct affinities of BoSG derivatives for the S-proteins of different SARS-CoV-2 strains, including wild type, N501Y (Alpha), K417T/E484K/N501Y (Gamma), and L542R (Delta) mutants, and stronger affinity for the N501Y-containing variants. Docking of the four possible monosulfated BoSG disaccharides in interactions with the N501Y mutant S-protein predicted potential binding poses of the BoSG constructs and favorable binding in close proximity to the 501Y residue. Our results demonstrate that depolymerization and fractionation of BoSG are an effective strategy to segregate its anticoagulant property from its anti-SARS-CoV-2 action.

4.
Pharmaceuticals (Basel) ; 15(2)2022 Feb 21.
Article in English | MEDLINE | ID: covidwho-1699238

ABSTRACT

With the increased prevalence of new SARS-CoV-2 variants of concern, such as Delta and Omicron, the COVID-19 pandemic has become an ongoing human health disaster, killing millions worldwide. 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, heparan sulfate (HS) on the surface of host cells plays an important role as a co-receptor for this viral pathogen-host cell interaction. Our previous studies demonstrated that many sulfated glycans, such as heparin, fucoidans, and rhamnan sulfate have anti-SARS-CoV-2 activities. In the current study, a small library of sulfated glycans and highly negatively charged compounds, including pentosan polysulfate (PPS), mucopolysaccharide polysulfate (MPS), sulfated lactobionic acid, sulodexide, and defibrotide, was assembled and evaluated for binding to the S-proteins and inhibition of viral infectivity in vitro. These compounds inhibited the interaction of the S-protein receptor-binding domain (RBD) (wild type and different variants) with immobilized heparin, a highly sulfated HS, as determined using surface plasmon resonance (SPR). PPS and MPS showed the strongest inhibition of interaction of heparin and S-protein RBD. The competitive binding studies showed that the IC50 of PPS and MPS against the S-protein RBD binding to immobilized heparin was ~35 nM and ~9 nM, respectively, much lower than the IC50 for soluble heparin (IC50 = 56 nM). Both PPS and MPS showed stronger inhibition than heparin on the S-protein RBD or spike pseudotyped lentiviral particles binding to immobilized heparin. Finally, in an in vitro cell-based assay, PPS and MPS exhibited strong antiviral activities against pseudotyped viral particles of SARS-CoV-2 containing wild-type or Delta S-proteins.

5.
Mar Drugs ; 19(12)2021 Nov 30.
Article in English | MEDLINE | ID: covidwho-1542656

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.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Deoxy Sugars/pharmacology , Mannans/pharmacology , Plant Extracts/pharmacology , SARS-CoV-2/drug effects , Seaweed , Antiviral Agents/therapeutic use , Aquatic Organisms , Deoxy Sugars/therapeutic use , Humans , Mannans/therapeutic use , Plant Extracts/therapeutic use , Protein Binding/drug effects , Spike Glycoprotein, Coronavirus/drug effects , Structure-Activity Relationship
6.
Diseases ; 9(4)2021 Nov 17.
Article in English | MEDLINE | ID: covidwho-1523904

ABSTRACT

Zoonotic diseases are infectious diseases that pass from animals to humans. These include diseases caused by viruses, bacteria, fungi, and parasites and can be transmitted through close contact or through an intermediate insect vector. Many of the world's most problematic zoonotic diseases are viral diseases originating from animal spillovers. The Spanish influenza pandemic, Ebola outbreaks in Africa, and the current SARS-CoV-2 pandemic are thought to have started with humans interacting closely with infected animals. As the human population grows and encroaches on more and more natural habitats, these incidents will only increase in frequency. Because of this trend, new treatments and prevention strategies are being explored. Glycosaminoglycans (GAGs) are complex linear polysaccharides that are ubiquitously present on the surfaces of most human and animal cells. In many infectious diseases, the interactions between GAGs and zoonotic pathogens correspond to the first contact that results in the infection of host cells. In recent years, researchers have made progress in understanding the extraordinary roles of GAGs in the pathogenesis of zoonotic diseases, suggesting potential therapeutic avenues for using GAGs in the treatment of these diseases. This review examines the role of GAGs in the progression, prevention, and treatment of different zoonotic diseases caused by viruses.

7.
J Biol Chem ; 297(4): 101207, 2021 10.
Article in English | MEDLINE | ID: covidwho-1415531

ABSTRACT

Certain sulfated glycans, including those from marine sources, can show potential effects against SARS-CoV-2. Here, a new fucosylated chondroitin sulfate (FucCS) from the sea cucumber Pentacta pygmaea (PpFucCS) (MW ∼10-60 kDa) was isolated and structurally characterized by NMR. PpFucCS is composed of {→3)-ß-GalNAcX-(1→4)-ß-GlcA-[(3→1)Y]-(1→}, where X = 4S (80%), 6S (10%) or nonsulfated (10%), Y = α-Fuc2,4S (40%), α-Fuc2,4S-(1→4)-α-Fuc (30%), or α-Fuc4S (30%), and S = SO3-. The anti-SARS-CoV-2 activity of PpFucCS and those of the FucCS and sulfated fucan isolated from Isostichopus badionotus (IbFucCS and IbSF) were compared with that of heparin. IC50 values demonstrated the activity of the three holothurian sulfated glycans to be ∼12 times more efficient than heparin, with no cytotoxic effects. The dissociation constant (KD) values obtained by surface plasmon resonance of the wildtype SARS-CoV-2 spike (S)-protein receptor-binding domain (RBD) and N501Y mutant RBD in interactions with the heparin-immobilized sensor chip were 94 and 1.8 × 103 nM, respectively. Competitive surface plasmon resonance inhibition analysis of PpFucCS, IbFucCS, and IbSF against heparin binding to wildtype S-protein showed IC50 values (in the nanomolar range) 6, 25, and 6 times more efficient than heparin, respectively. Data from computational simulations suggest an influence of the sulfation patterns of the Fuc units on hydrogen bonding with GlcA and that conformational change of some of the oligosaccharide structures occurs upon S-protein RBD binding. Compared with heparin, negligible anticoagulant action was observed for IbSF. Our results suggest that IbSF may represent a promising molecule for future investigations against SARS-CoV-2.


Subject(s)
Polysaccharides/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Sulfates/chemistry , Animals , Binding Sites , COVID-19/pathology , COVID-19/virology , Chondroitin Sulfates/chemistry , Chondroitin Sulfates/metabolism , Kinetics , Molecular Docking Simulation , Molecular Dynamics Simulation , Mutagenesis, Site-Directed , Partial Thromboplastin Time , Polysaccharides/chemistry , Protein Binding , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Sea Cucumbers/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Surface Plasmon Resonance
8.
Thromb J ; 19(1): 66, 2021 Sep 15.
Article in English | MEDLINE | ID: covidwho-1411428

ABSTRACT

BACKGROUND: This is a review article on heparin-induced thrombocytopenia, an adverse effect of heparin therapy, and vaccine-induced immune thrombotic thrombocytopenia, occurring in some patients administered certain coronavirus vaccines. MAIN BODY/TEXT: Immune-mediated thrombocytopenia occurs when specific antibodies bind to platelet factor 4 /heparin complexes. Platelet factor 4 is a naturally occurring chemokine, and under certain conditions, may complex with negatively charged molecules and polyanions, including heparin. The antibody-platelet factor 4/heparin complex may lead to platelet activation, accompanied by other cascading reactions, resulting in cerebral sinus thrombosis, deep vein thrombosis, lower limb arterial thrombosis, myocardial infarction, pulmonary embolism, skin necrosis, and thrombotic stroke. If untreated, heparin-induced thrombocytopenia can be life threatening. In parallel, rare incidents of spontaneous vaccine-induced immune thrombotic thrombocytopenia can also occur in some patients administered certain coronavirus vaccines. The role of platelet factor 4 in vaccine-induced thrombosis with thrombocytopenia syndrome further reinforces the importance the platelet factor 4/polyanion immune complexes and the complications that this might pose to susceptible individuals. These findings demonstrate, how auxiliary factors can complicate heparin therapy and drug development. An increasing interest in biomanufacturing heparins from non-animal sources has driven a growing interest in understanding the biology of immune-mediated heparin-induced thrombocytopenia, and therefore, the development of safe and effective biosynthetic heparins. SHORT CONCLUSION: In conclusion, these findings further reinforce the importance of the binding of platelet factor 4 with known and unknown polyanions, and the complications that these might pose to susceptible patients. In parallel, these findings also demonstrate how auxiliary factors can complicate the heparin drug development.

9.
Front Mol Biosci ; 8: 649575, 2021.
Article in English | MEDLINE | ID: covidwho-1285315

ABSTRACT

The severe acute respiratory syndrome (SARS)-like coronavirus disease (COVID-19) is caused by SARS-CoV-2 and has been a serious threat to global public health with limited treatment. Cellular heparan sulfate (HS) has been found to bind SARS-CoV-2 spike protein (SV2-S) and co-operate with cell surface receptor angiotensin-converting enzyme 2 (ACE2) to mediate SARS-CoV-2 infection of host cells. In this study, we determined that host cell surface SV2-S binding depends on and correlates with host cell surface HS expression. This binding is required for SARS-Cov-2 virus to infect host cells and can be blocked by heparin lyase, HS antagonist surfen, heparin, and heparin derivatives. The binding of heparin/HS to SV2-S is mainly determined by its overall sulfation with potential, minor contribution of specific SV2-S binding motifs. The higher binding affinity of SV2-S G614 mutant to heparin and upregulated HS expression may be one of the mechanisms underlying the higher infectivity of the SARS-CoV-2 G614 variant and the high vulnerability of lung cancer patients to SARS-CoV-2 infection, respectively. The higher host cell infection by SARS-CoV-2 G614 variant pseudovirus and the increased infection caused by upregulated HS expression both can be effectively blocked by heparin lyase and heparin, and possibly surfen and heparin derivatives too. Our findings support blocking HS-SV2-S interaction may provide one addition to achieve effective prevention and/treatment of COVID-19.

10.
Carbohydr Polym ; 260: 117797, 2021 May 15.
Article in English | MEDLINE | ID: covidwho-1084646

ABSTRACT

Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has resulted in a pandemic and continues to spread at an unprecedented rate around the world. Although a vaccine has recently been approved, there are currently few effective therapeutics to fight its associated disease in humans, COVID-19. SARS-CoV-2 and the related severe acute respiratory syndrome (SARS-CoV-1), and Middle East respiratory syndrome (MERS-CoV) result from zoonotic respiratory viruses that have bats as the primary host and an as yet unknown secondary host. While each of these viruses has different protein-based cell-surface receptors, each rely on the glycosaminoglycan, heparan sulfate as a co-receptor. In this study we compare, for the first time, differences and similarities in the structure of heparan sulfate in human and bat lungs. Furthermore, we show that the spike glycoprotein of COVID-19 binds 3.5 times stronger to human lung heparan sulfate than bat lung heparan sulfate.


Subject(s)
Heparitin Sulfate/metabolism , Lung/chemistry , Receptors, Virus/metabolism , SARS-CoV-2/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Animals , Chiroptera , Female , Heparitin Sulfate/chemistry , Heparitin Sulfate/isolation & purification , Humans , Male , Molecular Structure , Molecular Weight , Protein Binding , Receptors, Virus/chemistry , Receptors, Virus/isolation & purification
11.
J Virol ; 95(3)2021 01 13.
Article in English | MEDLINE | ID: covidwho-1048660

ABSTRACT

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has caused a pandemic of historic proportions and continues to spread globally, with enormous consequences to human health. Currently there is no vaccine, effective therapeutic, or prophylactic. As with other betacoronaviruses, attachment and entry of SARS-CoV-2 are mediated by the spike glycoprotein (SGP). In addition to its well-documented interaction with its receptor, human angiotensin-converting enzyme 2 (hACE2), SGP has been found to bind to glycosaminoglycans like heparan sulfate, which is found on the surface of virtually all mammalian cells. Here, we pseudotyped SARS-CoV-2 SGP on a third-generation lentiviral (pLV) vector and tested the impact of various sulfated polysaccharides on transduction efficiency in mammalian cells. The pLV vector pseudotyped SGP efficiently and produced high titers on HEK293T cells. Various sulfated polysaccharides potently neutralized pLV-S pseudotyped virus with clear structure-based differences in antiviral activity and affinity to SGP. Concentration-response curves showed that pLV-S particles were efficiently neutralized by a range of concentrations of unfractionated heparin (UFH), enoxaparin, 6-O-desulfated UFH, and 6-O-desulfated enoxaparin with 50% inhibitory concentrations (IC50s) of 5.99 µg/liter, 1.08 mg/liter, 1.77 µg/liter, and 5.86 mg/liter, respectively. In summary, several sulfated polysaccharides show potent anti-SARS-CoV-2 activity and can be developed for prophylactic as well as therapeutic purposes.IMPORTANCE The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV-2) in Wuhan, China, in late 2019 and its subsequent spread to the rest of the world has created a pandemic situation unprecedented in modern history. While ACE2 has been identified as the viral receptor, cellular polysaccharides have also been implicated in virus entry. The SARS-CoV-2 spike glycoprotein (SGP) binds to glycosaminoglycans like heparan sulfate, which is found on the surface of virtually all mammalian cells. Here, we report structure-based differences in antiviral activity and affinity to SGP for several sulfated polysaccharides, including both well-characterized FDA-approved drugs and novel marine sulfated polysaccharides, which can be developed for prophylactic as well as therapeutic purposes.


Subject(s)
Antiviral Agents/pharmacology , Heparin/pharmacology , SARS-CoV-2/drug effects , Virus Internalization/drug effects , Animals , Antiviral Agents/chemistry , Antiviral Agents/metabolism , Drug Evaluation, Preclinical , Enoxaparin/chemistry , Enoxaparin/metabolism , Enoxaparin/pharmacology , Genetic Vectors/genetics , HEK293 Cells , Heparin/chemistry , Heparin/metabolism , Heparitin Sulfate/metabolism , Humans , Inhibitory Concentration 50 , Lentivirus/genetics , Molecular Structure , Molecular Weight , Polysaccharides/chemistry , Polysaccharides/metabolism , Polysaccharides/pharmacology , Protein Binding , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Transduction, Genetic , Virus Attachment/drug effects
12.
Int J Biol Macromol ; 163: 1649-1658, 2020 Nov 15.
Article in English | MEDLINE | ID: covidwho-792418

ABSTRACT

The SARS-CoV-2 spike glycoproteins (SGPs) and human angiotensin converting enzyme 2 (ACE2) are the two key targets for the prevention and treatment of COVID-19. Host cell surface heparan sulfate (HS) is believed to interact with SARS-CoV-2 SGPs to facilitate host cell entry. In the current study, a series of polysaccharides from Saccharina japonica were prepared to investigate the structure-activity relationship on the binding abilities of polysaccharides (oligosaccharides) to pseudotype particles, including SARS-CoV-2 SGPs, and ACE2 using surface plasmon resonance. Sulfated galactofucan (SJ-D-S-H) and glucuronomannan (Gn) displayed strongly inhibited interaction between SARS-CoV-2 SGPs and heparin while showing negligible inhibition of the interaction between SARS-CoV-2 SGPs and ACE2. The IC50 values of SJ-D-S-H and Gn in blocking heparin SGP binding were 27 and 231 nM, respectively. NMR analysis showed that the structure of SJ-D-S-H featured with a backbone of 1, 3-linked α-L-Fucp residues sulfated at C4 and C2/C4 and 1, 3-linked α-L-Fucp residues sulfated at C4 and branched with 1, 6-linked ß-D-galacto-biose; Gn had a backbone of alternating 1, 4-linked ß-D-GlcAp residues and 1, 2-linked α-D-Manp residues. The sulfated galactofucan and glucuronomannan showed strong binding ability to SARS-CoV-2 SGPs, suggesting that these polysaccharides might be good candidates for preventing and/or treating SARS-CoV-2.


Subject(s)
Coronavirus Infections/virology , Glucuronates/metabolism , Mannose/analogs & derivatives , Pneumonia, Viral/virology , Polysaccharides/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Angiotensin-Converting Enzyme 2 , Betacoronavirus/chemistry , Betacoronavirus/metabolism , Binding Sites , COVID-19 , Glucuronates/chemistry , Heparin/chemistry , Heparin/metabolism , Humans , Mannose/chemistry , Mannose/metabolism , Oligosaccharides/chemistry , Pandemics , Peptidyl-Dipeptidase A/metabolism , Phaeophyta/chemistry , Polysaccharides/chemistry , Protein Binding , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry , Structure-Activity Relationship
14.
Antiviral Res ; 181: 104873, 2020 09.
Article in English | MEDLINE | ID: covidwho-638553

ABSTRACT

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has resulted in a pandemic and continues to spread around the globe at an unprecedented rate. To date, no effective therapeutic is available to fight its associated disease, COVID-19. Our discovery of a novel insertion of glycosaminoglycan (GAG)-binding motif at S1/S2 proteolytic cleavage site (681-686 (PRRARS)) and two other GAG-binding-like motifs within SARS-CoV-2 spike glycoprotein (SGP) led us to hypothesize that host cell surface GAGs may interact SARS-CoV-2 SGPs to facilitate host cell entry. Using a surface plasmon resonance direct binding assay, we found that both monomeric and trimeric SARS-CoV-2 SGP bind more tightly to immobilized heparin (KD = 40 pM and 73 pM, respectively) than the SARS-CoV and MERS-CoV SGPs (500 nM and 1 nM, respectively). In competitive binding studies, the IC50 of heparin, tri-sulfated non-anticoagulant heparan sulfate, and non-anticoagulant low molecular weight heparin against SARS-CoV-2 SGP binding to immobilized heparin were 0.056 µM, 0.12 µM, and 26.4 µM, respectively. Finally, unbiased computational ligand docking indicates that heparan sulfate interacts with the GAG-binding motif at the S1/S2 site on each monomer interface in the trimeric SARS-CoV-2 SGP, and at another site (453-459 (YRLFRKS)) when the receptor-binding domain is in an open conformation. The current study serves a foundation to further investigate biological roles of GAGs in SARS-CoV-2 pathogenesis. Furthermore, our findings may provide additional basis for further heparin-based interventions for COVID-19 patients exhibiting thrombotic complications.


Subject(s)
Betacoronavirus/metabolism , Coronavirus Infections/virology , Heparin/metabolism , Pandemics , Pneumonia, Viral/virology , Severe Acute Respiratory Syndrome/virology , Spike Glycoprotein, Coronavirus/metabolism , Binding Sites , COVID-19 , Humans , Kinetics , Molecular Docking Simulation , Protein Binding , SARS-CoV-2 , Surface Plasmon Resonance
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