Effective Inhibition of SARS-CoV-2 Entry by Heparin and Enoxaparin Derivatives.

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.

journal_name

J Virol

journal_title

Journal of virology

authors

Tandon R,Sharp JS,Zhang F,Pomin VH,Ashpole NM,Mitra D,McCandless MG,Jin W,Liu H,Sharma P,Linhardt RJ

doi

10.1128/JVI.01987-20

subject

Has Abstract

pub_date

2021-01-13 00:00:00

issue

3

eissn

0022-538X

issn

1098-5514

pii

JVI.01987-20

journal_volume

95

pub_type

杂志文章
  • Loss of viral gene expression and retention of tumorigenicity by Abelson lymphoma cells.

    abstract::Lymphomas induced by the Abelson murine leukemia virus (A-MuLV) were examined for the expression of biochemical and biological markers associated with A-MuLV transformation before and after in vivo growth in genetically distinguishable host mice. Although all tumors and clonal lines derived from them initially express...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.43.1.92-103.1982

    authors: Grunwald DJ,Dale B,Dudley J,Lamph W,Sugden B,Ozanne B,Risser R

    更新日期:1982-07-01 00:00:00

  • The effect of clade-specific sequence polymorphisms on HIV-1 protease activity and inhibitor resistance pathways.

    abstract::The majority of HIV-1 infections around the world result from non-B clade HIV-1 strains. The CRF01_AE (AE) strain is seen principally in Southeast Asia. AE protease differs by approximately 10% in amino acid sequence from clade B protease and carries several naturally occurring polymorphisms that are associated with d...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.00505-10

    authors: Bandaranayake RM,Kolli M,King NM,Nalivaika EA,Heroux A,Kakizawa J,Sugiura W,Schiffer CA

    更新日期:2010-10-01 00:00:00

  • Kaposi's sarcoma-associated herpesvirus lytic origin (ori-Lyt)-dependent DNA replication: identification of the ori-Lyt and association of K8 bZip protein with the origin.

    abstract::Herpesviruses utilize different origins of replication during lytic versus latent infection. Latent DNA replication depends on host cellular DNA replication machinery, whereas lytic cycle DNA replication requires virally encoded replication proteins. In lytic DNA replication, the lytic origin (ori-Lyt) is bound by a v...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/jvi.77.10.5578-5588.2003

    authors: Lin CL,Li H,Wang Y,Zhu FX,Kudchodkar S,Yuan Y

    更新日期:2003-05-01 00:00:00

  • Role of the Rous sarcoma virus p10 domain in shape determination of gag virus-like particles assembled in vitro and within Escherichia coli.

    abstract::Purified retrovirus Gag proteins can assemble in vitro into virus-like particles (VLPs) in the presence of RNA. It was shown previously that a Rous sarcoma virus Gag protein missing only the protease domain forms spherical particles resembling immature virions lacking a membrane but that a similar protein missing the ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/jvi.74.21.10260-10268.2000

    authors: Joshi SM,Vogt VM

    更新日期:2000-11-01 00:00:00

  • Molecular cloning and characterization of human papilloma virus DNA derived from a laryngeal papilloma.

    abstract::Papilloma virus DNA from a laryngeal papilloma was cloned in phage lambda L 47 and characterized after cleavage with different restriction enzymes. Hybridization with the DNAs of human papilloma virus types 1, 2, 3, 4, 5, and 8 showed no homology under stringent hybridization conditions. Human papilloma virus type 6 D...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.44.1.393-400.1982

    authors: Gissmann L,Diehl V,Schultz-Coulon HJ,zur Hausen H

    更新日期:1982-10-01 00:00:00

  • Posttranslational modification at the N terminus of the human adenovirus type 12 E1A 235R tumor antigen.

    abstract::The adenovirus E1A transforming region, which encodes immortalization, partial cell transformation, and gene activation functions, expresses two early mRNAs, 13S and 12S. Multiple-T antigen species with different electrophoretic mobilities are formed from each mRNA, presumably by unknown posttranslational modification...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.58.2.592-599.1986

    authors: Lucher LA,Brackmann KH,Symington JS,Green M

    更新日期:1986-05-01 00:00:00

  • Suppression of cellular proliferation by the papillomavirus E2 protein.

    abstract::Carcinogenic progression of a human papillomavirus (HPV)-infected cell is often associated with integration of the viral genome in a manner which results in the loss of expression of the viral regulatory protein E2. One function of E2 is the regulation of expression of the viral oncogenes, E6 and E7. Introduction of t...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.69.12.7791-7799.1995

    authors: Dowhanick JJ,McBride AA,Howley PM

    更新日期:1995-12-01 00:00:00

  • Design and intracellular activity of a human single-chain antibody to human immunodeficiency virus type 1 conserved gp41 epitope.

    abstract::A human lymphoid cell line (F172-D8) excreting a human immunodeficiency virus type 1 (HIV-1) anti-gp41 monoclonal antibody was used to construct a plasmid containing the cDNA of the single-chain variable fragment (scFvD8) corresponding to this antibody. A stable human osteosarcoma cell line was obtained which expresse...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/jvi.74.12.5712-5715.2000

    authors: Legastelois I,Desgranges C

    更新日期:2000-06-01 00:00:00

  • Cell-specific expression of RANTES, MCP-1, and MIP-1alpha by lower airway epithelial cells and eosinophils infected with respiratory syncytial virus.

    abstract::Respiratory syncytial virus (RSV) is the major cause of acute bronchiolitis in infancy, a syndrome characterized by wheezing, respiratory distress, and the pathologic findings of peribronchial mononuclear cell infiltration and release of inflammatory mediators by basophil and eosinophil leukocytes. Composition and act...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.72.6.4756-4764.1998

    authors: Olszewska-Pazdrak B,Casola A,Saito T,Alam R,Crowe SE,Mei F,Ogra PL,Garofalo RP

    更新日期:1998-06-01 00:00:00

  • Cross-reactivity between hepatitis C virus and Influenza A virus determinant-specific cytotoxic T cells.

    abstract::The cellular immune response contributes to viral clearance as well as to liver injury in acute and chronic hepatitis C virus (HCV) infection. An immunodominant determinant frequently recognized by liver-infiltrating and circulating CD8(+) T cells of HCV-infected patients is the HCV(NS3-1073) peptide CVNGVCWTV. Using ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.75.23.11392-11400.2001

    authors: Wedemeyer H,Mizukoshi E,Davis AR,Bennink JR,Rehermann B

    更新日期:2001-12-01 00:00:00

  • New genes from old: redeployment of dUTPase by herpesviruses.

    abstract::Published work (D. J. McGeoch, Nucleic Acids Res. 18:4105-4110, 1990; J. E. McGeehan, N. W. Depledge, and D. J. McGeoch, Curr. Protein Peptide Sci. 2:325-333, 2001) has indicated that evolution of dUTPase in the class of herpesviruses that infect mammals and birds involved capture of a host gene followed by a duplicat...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.79.20.12880-12892.2005

    authors: Davison AJ,Stow ND

    更新日期:2005-10-01 00:00:00

  • Effective ex vivo neutralization of human immunodeficiency virus type 1 in plasma by recombinant immunoglobulin molecules.

    abstract::We tested the ability of human monoclonal antibodies (immunoglobulin G1b12 [IgG1b12] and 19b) and CD4-based molecules (CD4-IgG2 and soluble CD4 [sCD4]) to neutralize human immunodeficiency virus type 1 directly from the plasma of seropositive donors in an ex vivo neutralization assay. IgG1b12 and CD4-IgG2, at concentr...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.70.4.2586-2592.1996

    authors: Gauduin MC,Allaway GP,Maddon PJ,Barbas CF 3rd,Burton DR,Koup RA

    更新日期:1996-04-01 00:00:00

  • Mutations in multiple domains activate paramyxovirus F protein-induced fusion.

    abstract::SER virus, a paramyxovirus that is closely related to simian virus 5 (SV5), is unusual in that it fails to induce syncytium formation. The SER virus F protein has an unusually long cytoplasmic tail (CT), and it was previously observed that truncations or specific mutations of this domain result in enhanced syncytium f...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.78.16.8513-8523.2004

    authors: Seth S,Goodman AL,Compans RW

    更新日期:2004-08-01 00:00:00

  • Chromosomal sites for hepatitis B virus integration in human hepatocellular carcinoma.

    abstract::The discovery that hepatitis B virus (HBV) integrates into host chromosomes raises the question of whether such viral DNA integration correlates directly with the activation of specific oncogenes or the inactivation of anti-oncogenes. To obtain insight into this problem, we randomly collected HBV integrant samples fro...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.65.12.6761-6764.1991

    authors: Tokino T,Matsubara K

    更新日期:1991-12-01 00:00:00

  • The human papillomavirus type 8 E2 protein suppresses beta4-integrin expression in primary human keratinocytes.

    abstract::Human papillomaviruses (HPVs) infect keratinocytes of skin and mucosa. Homeostasis of these constantly renewing, stratified epithelia is maintained by balanced keratinocyte proliferation and terminal differentiation. Instructions from the extracellular matrix engaging integrins strongly regulate these keratinocyte fun...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.78.19.10738-10746.2004

    authors: Oldak M,Smola H,Aumailley M,Rivero F,Pfister H,Smola-Hess S

    更新日期:2004-10-01 00:00:00

  • Dengue virus-specific human CD4+ T-lymphocyte responses in a recipient of an experimental live-attenuated dengue virus type 1 vaccine: bulk culture proliferation, clonal analysis, and precursor frequency determination.

    abstract::We analyzed the CD4+ T-lymphocyte responses to dengue, West Nile, and yellow fever viruses 4 months after immunization of a volunteer with an experimental live-attenuated dengue virus type 1 vaccine (DEN-1 45AZ5). We examined bulk culture proliferation to noninfectious antigens, determined the precursor frequency of s...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.67.10.5962-5967.1993

    authors: Green S,Kurane I,Edelman R,Tacket CO,Eckels KH,Vaughn DW,Hoke CH Jr,Ennis FA

    更新日期:1993-10-01 00:00:00

  • Vesicular stomatitis virus matrix protein impairs CD1d-mediated antigen presentation through activation of the p38 MAPK pathway.

    abstract::Natural killer T (NKT) cells are unique T lymphocytes that recognize CD1d-bound lipid antigens and play an important role in both innate and acquired immune responses against infectious diseases and tumors. We have already shown that a vesicular stomatitis virus (VSV) infection results in the rapid inhibition of murin...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.00881-08

    authors: Renukaradhya GJ,Khan MA,Shaji D,Brutkiewicz RR

    更新日期:2008-12-01 00:00:00

  • Characterization of the protease of a fish retrovirus, walleye dermal sarcoma virus.

    abstract::Three fish retroviruses infecting walleyes constitute the recently recognized genus called epsilonretrovirus. The founding member of this group, walleye dermal sarcoma virus (WDSV), induces benign skin tumors in the infected fish and replicates near 4 degrees C. While the viral genomic sequence is known, biochemical c...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/jvi.76.9.4341-4349.2002

    authors: Fodor SK,Vogt VM

    更新日期:2002-05-01 00:00:00

  • Mutations of the RNase H C helix of the Moloney murine leukemia virus reverse transcriptase reveal defects in polypurine tract recognition.

    abstract::Both the RNase H domain of Moloney murine leukemia virus (Mo-MLV) reverse transcriptase (RT) and Escherichia coli RNase H possess a positively charged alpha-helix (C helix) and a loop that are not present in the RNase H domains of human immunodeficiency virus (HIV) RT or avian sarcoma virus RT. Although a mutant Mo-ML...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/jvi.76.16.8360-8373.2002

    authors: Lim D,Orlova M,Goff SP

    更新日期:2002-08-01 00:00:00

  • Replication of hepatitis delta virus RNA: effect of mutations of the autocatalytic cleavage sites.

    abstract::Hepatitis delta virus (HDV) contains a circular RNA genome of 1.7 kb. HDV RNA replication is thought to proceed via a rolling-circle mechanism that is dependent on autocatalytic cleavage and ligation reactions. However, it has never been established that these ribozyme activities are indeed involved in HDV RNA replica...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.67.4.2228-2234.1993

    authors: Macnaughton TB,Wang YJ,Lai MM

    更新日期:1993-04-01 00:00:00

  • Inter- and intragenus structural variations in caliciviruses and their functional implications.

    abstract::The family Caliciviridae is divided into four genera and consists of single-stranded RNA viruses with hosts ranging from humans to a wide variety of animals. Human caliciviruses are the major cause of outbreaks of acute nonbacterial gastroenteritis, whereas animal caliciviruses cause various host-dependent illnesses w...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.78.12.6469-6479.2004

    authors: Chen R,Neill JD,Noel JS,Hutson AM,Glass RI,Estes MK,Prasad BV

    更新日期:2004-06-01 00:00:00

  • L protein requirement for in vitro RNA synthesis by vesicular stomatitis virus.

    abstract::The endogenous transcriptase present in purified vesicular stomatitis (VS) virions was solubilized with a Triton X-100 high-salt solution. The polymerase activity was purified on glycerol gradients and by phosphocellulose column chromatography; the viral proteins present in the active enzyme fractions were identified ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.12.6.1325-1335.1973

    authors: Emerson SU,Wagner RR

    更新日期:1973-12-01 00:00:00

  • Late-phase expression of a murine cytomegalovirus immediate-early antigen recognized by cytolytic T lymphocytes.

    abstract::The cloned murine cytolytic T-lymphocyte line IE1-IL and several sublines detect a murine cytomegalovirus immediate-early (IE) membrane determinant in conjunction with Ld class I major histocompatibility glycoprotein. The lines retained cytolytic activity, strict antigen specificity, and self-restriction even when ada...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.60.3.1125-1129.1986

    authors: Reddehase MJ,Fibi MR,Keil GM,Koszinowski UH

    更新日期:1986-12-01 00:00:00

  • A carboxy-terminally truncated human CPSF6 lacking residues encoded by exon 6 inhibits HIV-1 cDNA synthesis and promotes capsid disassembly.

    abstract::Since HIV-1 replication is modulated at multiple stages by host cell factors, identification and characterization of those host cell factors are expected to contribute to the development of novel anti-HIV therapeutics. Previous studies showed that a C-terminally truncated cytosolic form of cleavage and polyadenylation...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.00124-13

    authors: Hori T,Takeuchi H,Saito H,Sakuma R,Inagaki Y,Yamaoka S

    更新日期:2013-07-01 00:00:00

  • A hairpin structure in the R region of the human immunodeficiency virus type 1 RNA genome is instrumental in polyadenylation site selection.

    abstract::Some retroviruses with an extended repeat (R) region encode the polyadenylation signal within the R region such that this signal is present at both the 5' and 3' ends of the viral transcript. This necessitates differential regulation to either repress recognition of the 5' polyadenylation signal or enhance usage of th...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.73.1.81-91.1999

    authors: Das AT,Klaver B,Berkhout B

    更新日期:1999-01-01 00:00:00

  • Interactions of the cytoplasmic domains of human and simian retroviral transmembrane proteins with components of the clathrin adaptor complexes modulate intracellular and cell surface expression of envelope glycoproteins.

    abstract::The cytoplasmic domains of the transmembrane (TM) envelope proteins (TM-CDs) of most retroviruses have a Tyr-based motif, YXXO, in their membrane-proximal regions. This signal is involved in the trafficking and endocytosis of membrane receptors via clathrin-associated AP-1 and AP-2 adaptor complexes. We have used CD8-...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.73.2.1350-1361.1999

    authors: Berlioz-Torrent C,Shacklett BL,Erdtmann L,Delamarre L,Bouchaert I,Sonigo P,Dokhelar MC,Benarous R

    更新日期:1999-02-01 00:00:00

  • Analysis of DNA sequences which regulate the transcription of a herpes simplex virus immediate early gene.

    abstract::The locations and functions of DNA sequences involved in transcription of the gene encoding herpes simplex virus type 1 immediate early (IE) mRNAs 4 and 5 were analyzed by use of a transient-expression assay. The region upstream of the genes encoding IE mRNAs 4 and 5 was fused to the thymidine kinase gene coding seque...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.50.3.708-716.1984

    authors: Preston CM,Cordingley MG,Stow ND

    更新日期:1984-06-01 00:00:00

  • Measles virus fusion: role of the cysteine-rich region of the fusion glycoprotein.

    abstract::Measles virus (MV) fusion requires the participation of both the fusion (F) and hemagglutinin (H) glycoproteins. The canine distemper virus fusion protein (CDVF) cannot substitute for the measles virus fusion protein (MVF) in this process. Introduction of restriction enzyme sites into the cDNAs of CDVF and MVF by site...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.68.11.7546-7548.1994

    authors: Wild TF,Fayolle J,Beauverger P,Buckland R

    更新日期:1994-11-01 00:00:00

  • Tryptic peptide analysis of gag gene proteins of endogenous mouse type C viruses.

    abstract::Tryptic digests of the internal proteins p30, p15, p12, and p10 of mouse xenotropic, ecotropic, and amphotropic type C viruses were subjected to cation-exchange chromatography. Analysis of these maps revealed that the p30 proteins from representative isolates of all three viral subgroups were distinguishable. The p15 ...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.29.1.102-113.1979

    authors: Albino A,Korngold L,Mellors RC

    更新日期:1979-01-01 00:00:00

  • Severe acute respiratory syndrome coronavirus papain-like protease ubiquitin-like domain and catalytic domain regulate antagonism of IRF3 and NF-kappaB signaling.

    abstract::The outcome of a viral infection is regulated in part by the complex coordination of viral and host interactions that compete for the control and optimization of virus replication. Severe acute respiratory syndrome coronavirus (SARS-CoV) intimately engages and regulates the host innate immune responses during infectio...

    journal_title:Journal of virology

    pub_type: 杂志文章

    doi:10.1128/JVI.02220-08

    authors: Frieman M,Ratia K,Johnston RE,Mesecar AD,Baric RS

    更新日期:2009-07-01 00:00:00