A Highly Potent SARS-CoV-2 Blocking Lectin Protein

Ahan, Recep Erdem; Hanifehnezhad, Alireza; Kehribar, Ebru Şahin; Oğuzoğlu, Tuba Çiğdem; Földes, Katalin; Özçelik, Cemile Elif; Filazi, Nazlican; Öztop, Sıdıka; Önder, Sevgen; Bozkurt, Eray Ulaş; Ergünay, Koray; Özkul, Aykut; Şeker, Urartu Özgür Şafak

doi:10.1101/2021.07.22.453309

Cited by 3 publications

(4 citation statements)

References 56 publications

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“…The IC 50 values of the weight concentration (1.6 lgÁmL À1 for both the strains), which is typically used for comparisons among antibodies, were comparable to the value of 0.71 lgÁmL À1 obtained for FRIL by a similar PRNT assay [19]. The values were also comparable to the 0.42 lgÁmL À1 obtained for GRFT based on a quantitative reverse-transcription/real-time PCR (qRT-PCR) assay [20], and much stronger than the 50-100 lgÁmL À1 for CLEC4G or CD209C obtained by qRT-PCR [18]. Therefore, PhoSL is among the most potent lectins for inhibition of SARS-CoV-2 infection.…”

Section: Neutralisation Of Sars-cov-2 Infection By Phoslsupporting

confidence: 73%

“…C‐type lectins related to the above, namely, CD209 antigen‐like protein C (CD209C) and C‐type lectin domain family 4 member G (CLEC4G), were found to show high affinities with S protein and inhibitory effects on SARS‐CoV‐2 infection [18]. These activities have also been demonstrated for lectins of non‐mammalian origins, namely, Flt3 receptor‐interacting lectin (FRIL) isolated from hyacinth bean [19], and Griffithsin (GRFT) isolated from red alga [20]. To use these lectins as drugs, the off‐target effects, including blood coagulation, should be reduced.…”

Section: Introductionmentioning

confidence: 99%

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Core fucose‐specific Pholiota squarrosa lectin (PhoSL) as a potent broad‐spectrum inhibitor of SARS‐CoV‐2 infection

et al. 2022

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Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) spike protein (S protein) is highly N‐glycosylated, and a “glycan shield” is formed to limit the access of other molecules; however, a small open area coincides with the interface to the host's receptor and also neutralising antibodies. Most of the variants of concern have mutations in this area, which could reduce the efficacy of existing antibodies. In contrast, N‐glycosylation sites are relatively invariant, and some are essential for infection. Here, we observed that the S proteins of the ancestral (Wuhan) and Omicron strains bind with Pholiota squarrosa lectin (PhoSL), a 40‐amino‐acid chemically synthesised peptide specific to core‐fucosylated N‐glycans. The affinities were at a low nanomolar level, which were ~ 1000‐fold stronger than those between PhoSL and the core‐fucosylated N‐glycans at the micromolar level. We demonstrated that PhoSL inhibited infection by both strains at similar submicromolar levels, suggesting its broad‐spectrum effect on SARS‐CoV‐2 variants. Cryogenic electron microscopy revealed that PhoSL caused an aggregation of the S protein, which was likely due to the multivalence of both the trimeric PhoSL and S protein. This characteristic is likely relevant to the inhibitory mechanism. Structural modelling of the PhoSL–S protein complex indicated that PhoSL was in contact with the amino acids of the S protein, which explains the enhanced affinity with S protein and also indicates the significant potential for developing specific binders by the engineering of PhoSL.

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Section: Neutralisation Of Sars-cov-2 Infection By Phoslsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Core fucose‐specific Pholiota squarrosa lectin (PhoSL) as a potent broad‐spectrum inhibitor of SARS‐CoV‐2 infection

et al. 2022

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“…BOA and OAA belong to the same structural family and bind to identical sugar substructures of high mannose glycans ( 22, 24 ), whereas GRFT is structurally very different and binds to the terminal sugars in the D2 and D3 arms of high mannose glycans ( 25 ). Unfortunately, conflicting reports on GRFT’s activity towards SARS-CoV-2 infection exist, describing very different EC 50 values of 6 nM ( 41 ) or 300 nM ( 42 ). Since we did not observe any inhibition at 80 nM GRFT concentration, our results are in line with the data reported by the Jiang lab (26).…”

Section: Discussionmentioning

confidence: 99%

Targeting Spike Glycans to Inhibit SARS-CoV2 Viral Entry

Guseman

Rennick

Nambulli

et al. 2022

Preprint

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SARS-CoV-2 Spike harbors glycans which function as ligands for lectins. Therefore, it should be possible to exploit lectins to target SARS-CoV-2 and inhibit cellular entry by binding glycans on the Spike protein. Burkholderia oklahomensis agglutinin (BOA) is an antiviral lectin that interacts with viral glycoproteins via N-linked high mannose glycans. Here, we show that BOA binds to the Spike protein and is a potent inhibitor of SARS-CoV-2 viral entry at nanomolar concentrations. Using a variety of biophysical tools, we demonstrate that the interaction is avidity driven and that BOA crosslinks the Spike protein into soluble aggregates. Furthermore, using virus neutralization assays, we demonstrate that BOA effectively inhibits all tested variants of concern as well as SARS-CoV 2003, establishing that glycan-targeting molecules have the potential to be pan-coronavirus inhibitors.

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“…For the surface coating, the chip was incubated in 20 mM 110mercaptoundecanoic acid (11-MUA) at room temperature overnight. The activation of the surface was performed by EDC/NHS coupling reaction, and then protein immobilization was achieved, as previously described 50 . Each analysis was done by immobilization of 50 μg of S protein, which was followed by surface deactivation.…”

Section: Qcm Measurements For Determining Peptide-protein Interaction...mentioning

confidence: 99%

Screening Peptide Drug Candidates to Neutralize Whole Viral Agents : A Case study with SARS-CoV-2 Virus

Özçelik,

Araz,

Yılmaz

et al. 2023

Preprint

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Covid19 pandemic revealed the reality for the need of therapeutic and pharmaceutical molecule development in a short time with different approaches. Although the enhancement of immunological memory by vaccination was the quicker and robust strategy, still medication is required for immediate treatment for a patient. For this purpose, one of the approaches is developing new therapeutic molecule development like peptide-based drugs. Also, peptides can be used developing other molecules like nanobodies. Here, M13 phage display library was used for selecting SARS-CoV-2 interacting peptides for developing a neutralizing molecule for further use. Biopanning was applied with four iterative cycles to select phages displaying different 12-amino acid-long peptides. Then, the M13 phage genomic region where peptide sequences expressed were analyzed and sequences were obtained. Randomly selected peptide sequences were synthesized by solid-state peptide synthesis method. These peptides were analyzed by quartz crystal microbalance method in terms or peptide interaction capacity with specifically wild-type S protein. Next, QCM data was further validated by enzyme-linked immunosorbent assay (ELISA) in order to check peptides according to their neutralizing capacity rather than binding to S1 protein. The results showed that, phage display served an opportunity for selecting peptides which can be used and developed further as pharmaceutical molecules. More specifically, scpep3, scpep8 and scpep10 had both binding and neutralizing capacity for S1 protein as a candidate for therapeutic molecule.

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A Highly Potent SARS-CoV-2 Blocking Lectin Protein

Cited by 3 publications

References 56 publications

Core fucose‐specific Pholiota squarrosa lectin (PhoSL) as a potent broad‐spectrum inhibitor of SARS‐CoV‐2 infection

Core fucose‐specific Pholiota squarrosa lectin (PhoSL) as a potent broad‐spectrum inhibitor of SARS‐CoV‐2 infection

Targeting Spike Glycans to Inhibit SARS-CoV2 Viral Entry

Screening Peptide Drug Candidates to Neutralize Whole Viral Agents : A Case study with SARS-CoV-2 Virus

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