Targeted disruption of pi–pi stacking in Malaysian banana lectin reduces mitogenicity while preserving antiviral activity

Covés-Datson, Evelyn M.; King, Serina; Legendre, Maureen; Swanson, Meghan R.; Gupta, Auroni; Claes, Sandra; Meagher, Jennifer L.; Boonen, Arnaud; Zhang, Lihong; Kalveram, Birte; Raglow, Zoe; Freiberg, Alexander N.; Prichard, Mark N.; Stuckey, Jeanne A.; Schols, Dominique; Markovitz, David M.

doi:10.1038/s41598-020-80577-7

Cited by 19 publications

(23 citation statements)

References 34 publications

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“…Wild-type BanLec is active against additional pathogens, including bovine viral diarrheal virus (BVDV) and bovine alphaherpesvirus 1 (BoHV-1) 24 and Salmonella 25 . Interestingly, when a change similar to that which converted BanLec to H84T BanLec was made in the related Malaysian banana lectin, producing F84T Malay BanLec, broad-spectrum antiviral activity was retained and mitogenicity was reduced in a manner comparable to H84T BanLec 26 .…”

Section: Introductionmentioning

confidence: 99%

H84T BanLec has broad spectrum antiviral activity against human herpesviruses in cells, skin, and mice

Lloyd

Liu

Legendre

et al. 2022

Sci Rep

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H84T BanLec is a molecularly engineered lectin cloned from bananas with broad-spectrum antiviral activity against several RNA viruses. H84T BanLec dimers bind glycoproteins containing high-mannose N-glycans on the virion envelope, blocking attachment, entry, uncoating, and spread. It was unknown whether H84T BanLec is effective against human herpesviruses varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and herpes simplex virus 1 (HSV-1), which express high-mannose N-linked glycoproteins on their envelopes. We evaluated H84T BanLec against VZV-ORF57-Luc, TB40/E HCMV-fLuc-eGFP, and HSV-1 R8411 in cells, skin organ culture, and mice. The H84T BanLec EC50 was 0.025 µM for VZV (SI50 = 4000) in human foreskin fibroblasts (HFFs), 0.23 µM for HCMV (SI50 = 441) in HFFs, and 0.33 µM for HSV-1 (SI50 = 308) in Vero cells. Human skin was obtained from reduction mammoplasties and prepared for culture. Skin was infected and cultured up to 14 days. H84T BanLec prevented VZV, HCMV and HSV-1 spread in skin at 10 µM in the culture medium, and also exhibited dose-dependent antiviral effects. Additionally, H84T BanLec arrested virus spread when treatment was delayed. Histopathology of HCMV-infected skin showed no overt toxicity when H84T BanLec was present in the media. In athymic nude mice with human skin xenografts (NuSkin mice), H84T BanLec reduced VZV spread when administered subcutaneously prior to intraxenograft virus inoculation. This is the first demonstration of H84T BanLec effectiveness against DNA viruses. H84T BanLec may have additional unexplored activity against other, clinically relevant, glycosylated viruses.

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Section: Introductionmentioning

confidence: 99%

H84T BanLec has broad spectrum antiviral activity against human herpesviruses in cells, skin, and mice

Lloyd

Liu

Legendre

et al. 2022

Sci Rep

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“…Due to the fact of their high molecular size, which favors the synthesis of anti-lectin antibodies, and their mitogenic/cytotoxic properties, which interfere with the cytokine response of infected individuals, their use is limited to external treatments. However, the promising results obtained with a single-mutated engineered banana lectin, BanLec, which retains its carbohydrate-binding ability but loses its mitogenic property [46,47], could pave the way for the forthcoming production of innocuous mutated plant lectins available for a therapeutic use.…”

Section: Discussionmentioning

confidence: 99%

“…The effects of plant lectins on other pathogenic enveloped viruses have been more scarcely investigated. Plant lectins were identified as blocking agents for the entry of IV [45,52,57], HSV [57], HCMV [47,53,54], EBOV [47,48], LASV [47], and the coronaviruses MERS-CoV [51], SARS-CoV [42,51,54,62,63,104], and SARS-CoV-2 [50][51][52]58,60,61,66] in their corresponding host cells. However, depending on the viruses, the envelope glycoprotein(s) targeted by plant lectins are extremely diverse as mentioned in Table 2.…”

Section: How Can the Infectivity Of Pathogenic Enveloped Viruses Be Affected By Lectins?mentioning

confidence: 99%

“…However, depending on the viruses, the envelope glycoprotein(s) targeted by plant lectins are extremely diverse as mentioned in Table 2. In this respect, an engineered banana lectin, BanLec, which has lost its mitogenic potential but retained its mannose-binding property, interacted with the envelope E-glycoprotein and inhibited both the entry and replication of Ebola virus in cell cultures [47,48]. The cyanobacterial lectin, cyanovirin-N (CV-N), also displayed similar inhibition towards Ebola virus [85].…”

Section: How Can the Infectivity Of Pathogenic Enveloped Viruses Be Affected By Lectins?mentioning

confidence: 99%

“…However, plant lectins readily differ from each other by their capacity to elicit a cytokine production, some of them, such as PHA, Con A, and cyanovirin-N, being more active to induce the synthesis and release of activation markers [144,145], while Man-specific GNA-like lectins, such as GNA and HHA, were virtually incapable of triggering a relevant cytokine production [145,146]. Recently, a single-point mutation performed on an engineered banana lectin, BanLec, and an engineered Malaysian banana lectin, Malay BanLec, allowed to produce an active Man-binding lectin significantly devoid of mitogenic/cytotoxic activity [46,47]. If applicable for other Man-specific lectins, this point mutation approach would be an elegant way to attenuate or suppress the unwanted mitogenic/cytotoxic effects of lectins on target cells.…”

Section: Biomedical Perspectives For Antiviral Lectinsmentioning

confidence: 99%

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Legume Lectins with Different Specificities as Potential Glycan Probes for Pathogenic Enveloped Viruses

Barre

Damme

Klonjkowski

et al. 2022

Cells

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Pathogenic enveloped viruses are covered with a glycan shield that provides a dual function: the glycan structures contribute to virus protection as well as host cell recognition. The three classical types of N-glycans, in particular complex glycans, high-mannose glycans, and hybrid glycans, together with some O-glycans, participate in the glycan shield of the Ebola virus, influenza virus, human cytomegalovirus, herpes virus, human immunodeficiency virus, Lassa virus, and MERS-CoV, SARS-CoV, and SARS-CoV-2, which are responsible for respiratory syndromes. The glycans are linked to glycoproteins that occur as metastable prefusion glycoproteins on the surface of infectious virions such as gp120 of HIV, hemagglutinin of influenza, or spike proteins of beta-coronaviruses. Plant lectins with different carbohydrate-binding specificities and, especially, mannose-specific lectins from the Vicieae tribe, such as pea lectin and lentil lectin, can be used as glycan probes for targeting the glycan shield because of their specific interaction with the α1,6-fucosylated core Man3GlcNAc2, which predominantly occurs in complex and hybrid glycans. Other plant lectins with Neu5Ac specificity or GalNAc/T/Tn specificity can also serve as potential glycan probes for the often sialylated complex glycans and truncated O-glycans, respectively, which are abundantly distributed in the glycan shield of enveloped viruses. The biomedical and therapeutical potential of plant lectins as antiviral drugs is discussed.

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Plant lectins as versatile tools to fight coronavirus outbreaks

et al. 2022

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The S protein forming the homotrimeric spikes of pathogenic beta-coronaviruses, such as MERS-CoV, SARS-CoV and SARS-CoV-2, is a highly glycosylated protein containing mainly N -glycans of the complex and high-mannose type, as well as O -glycans. Similarly, the host cell receptors DPP4 for MERS-CoV and ACE2 for SARS-CoV and SARS-CoV-2, also represent N - and O -glycosylated proteins. All these glycoproteins share common glycosylation patterns, suggesting that plant lectins with different carbohydrate-binding specificities could be used as carbohydrate-binding agents for the spikes and their receptors, to combat COVID19 pandemics. The binding of plant lectins to the spikes and their receptors could mask the non-glycosylated receptor binding domain of the virus and the corresponding region of the receptor, thus preventing a proper interaction of the spike proteins with their receptors. In this review, we analyze (1) the ability of plant lectins to interact with the N - and O -glycans present on the spike proteins and their receptors, (2) the in vitro and in vivo anti-COVID19 activity already reported for plant lectins and, (3) the possible ways for delivery of lectins to block the spikes and/or their receptors.

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Targeted disruption of pi–pi stacking in Malaysian banana lectin reduces mitogenicity while preserving antiviral activity

Cited by 19 publications

References 34 publications

H84T BanLec has broad spectrum antiviral activity against human herpesviruses in cells, skin, and mice

H84T BanLec has broad spectrum antiviral activity against human herpesviruses in cells, skin, and mice

Legume Lectins with Different Specificities as Potential Glycan Probes for Pathogenic Enveloped Viruses

Plant lectins as versatile tools to fight coronavirus outbreaks

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