Els J. M. Van Damme

Pierre Rougé

Frontiers in Cellular and Infection Microbiology

PubMed

Van Damme, Els J. M.

Rougé, Pierre

PubMed Central

Editorial: Lectins from plants, algae, fungi, bacteria and animal therapeutic tools for SARS-CoV-2 and other pathogenic enveloped viruses, in a “one-health” perspective

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Frontiers in Cellular and Infection MicrobiologyOPEN ACCESSEDITED AND REVIEWED BYCurtis Brandt,University of Wisconsin-Madison,United States*CORRESPONDENCEEls J. M. Van DammeElsJM.VanDamme@ugent.beSPECIALTY SECTIONThis article was submitted toVirus and Host,a section of the journalFrontiers in Cellular andInfection MicrobiologyRECEIVED 07 January 2023ACCEPTED 13 January 2023PUBLISHED 23 January 2023CITATIONVan Damme EJM and Rougé P(2023) Editorial: Lectins from plants,algae, fungi, bacteria and animaltherapeutic tools for SARS-CoV-2and other pathogenic envelopedviruses, in a “one-health” perspective.Front. Cell. Infect. Microbiol. 13:1139691.doi: 10.3389/fcimb.2023.1139691COPYRIGHT© 2023 Van Damme and Rougé. This is anopen-access article distributed under theterms of the Creative Commons AttributionLicense (CC BY). The use, distribution orreproduction in other forums is permitted,provided the original author(s) and thecopyright owner(s) are credited and thatthe original publication in this journal iscited, in accordance with acceptedacademic practice. No use, distribution orreproduction is permitted which does notcomply with these terms.TYPE EditorialPUBLISHED 23 January 2023DOI 10.3389/fcimb.2023.1139691Editorial: Lectins from plants,algae, fungi, bacteria and animaltherapeutic tools for SARS-CoV-2and other pathogenicenveloped viruses, in a“one-health” perspectiveEls J. M. Van Damme1* and Pierre Rougé21Biotechnology, Ghent University, Ghent, Belgium, 2Pharmadev, Université Toulouse III Paul Sabatier,Toulouse, FranceKEYWORDSenveloped virus, lectin, glycan, carbohydrate recognition, carbohydrate-binding agentEditorial on the Research TopicLectins from plants, algae, fungi, bacteria and animals as potential ther-apeutic tools for SARS-CoV-2 and other pathogenic enveloped viruses, ina “one-health” perspectiveLectins or carbohydrate-binding agents (CBAs) from diverse sources including plants,algae, fungi, cyanobacteria and animals, can recognize the glycan chains decoratingpathogenic enveloped viruses, and consequently offer an interesting alternative toantibodies and antiviral drugs for combating viral infections. Most of the pathogenicenveloped viruses are highly N-glycosylated and exhibit surface glycoproteins containingdifferent types of N-glycans, including complex-type glycans, high-mannose- oroligomannoside-type glycans, and hybrid-type glycans, representing potential targets forlectins with different carbohydrate-binding specificities (Barre et al., 2022). In this regard,the perspective paper from Maier, demonstrated that natural cyanovirin-N (CV-N), themannose-specific lectin from the cyanobacterium Nostoc ellipsosporum, specificallyrecognizes N-glycans of the high-mannose type occurring on the surface ofhemagglutinin from influenza virus, gp120 from human immunodeficiency virus 1(HIV-1) and spike protein S from SARS-CoV and SARS-CoV-2. In addition, anengineered recombinant cyanovirin-N (CV-N) domain-swapped dimer with enhancedbinding capacities towards SARS-CoV-2 showed increased binding affinity to the highly N-glycosylated spike protein and hemagglutinin. These engineered CV-N dimers withenhanced binding capacities could be used to improve the neutralization ability of thelectin towards pathogenic enveloped viruses by reducing both the internalization and thespreading of the viruses.However, the antiviral activity of lectins is not limited to hampering or preventing therecognition and subsequent anchorage of the viral particles to the host cells. The OriginalResearch article of Vanhulle et al., brings interesting insights into the antiviral activity of thestinging nettle (Urtica dioica) lectin UDA, a small monomeric lectin with a specificity forfrontiersin.org01Van Damme and Rougé 10.3389/fcimb.2023.1139691GlcNAc, towards the SARS-CoV-2 Wuhan-Hu-1 strain and otherSARS-CoV-2 variants of concern (VOCs). At nanomolarconcentration, UDA prevented the viral replication of the SARS-CoV-2 Wuhan in Vero E6 cells but also the replication of SARS-CoV-2 VOCs Alpha, Beta and Gamma. Similarly, UDA inhibited the viralreplication of VOCs Delta and Omicron in U87.ACE2+ cells. Theseresults demonstrate that the antiviral activity of UDA relies primarilyon the recognition of the glycan shield, which is apparently similarlyN- and O-glycosylated in the SARS-CoV-2 WT and the VOCs.However, in addition to interfere with the anchorage andsubsequent entry of SARS-CoV-2 WT and VOCs into the hostcells, UDA also appears as a potent fusion inhibitor for thebetacoronaviruses, as shown from cell-cell fusion experiments.Finally, the S1 N-terminal part of the SARS-CoV-2 spike proteinwas identified as the main target for UDA since SARS-CoV-2 mutantsexhibiting N-glycosylation deletions in the S2 C-terminal portion ofthe spike protein, remained sensitive to the antiviral activity of UDA.Another well-known algal lectin with a specificity for mannose,griffithsin (GRFT), was investigated for its antiviral properties in vitroand in vivo towards the Hantaan virus (HTNV) responsible forhemorrhagic fever in East Asia, in the Original Research articlefrom Zhao et al.. In vitro experiments using recombinant vesicularstomatitis virus (rVSV) bearing HTNV glycoproteins revealed thatGRFT inhibited the entry of rVSV-HTNV in cultured host cells, bybinding to the HTNV N-glycans and preventing the virus frominteracting with the cellular receptors and subsequent entry in thecells. In addition, a reduction in mouse mortality of suckling miceinfected by HTNV, was obtained after GRFT treatment. These resultssuggest that GRFT could be a promising therapeutic agent forpreventing and treating the HTNV infection.Finally, the Original Research article from Nabeta et al., addressesthe antifungal activity of an engineered griffithsin (Q-GRFT) with animproved stability, for inhibiting Candida infection in murine modelsof vaginal candidiasis. In vivo experiments showed that Q-GRFTtreatment of infected mice significantly lowered the fungal burden,compared with the infected non-treated mice. In addition, a repeatedQ-GRFT treatment over 7 days enhanced the clearance of vaginalcandidiasis in previously infected mice. A histological control ofvaginal tissues confirmed the efficacy of the Q-GRFT treatment oninfected mice. These in vivo results demonstrate that griffithsin caninhibit Candida growth, and in vitro experiments suggest that theinhibitory effect is independent of the inflammatory immuneresponse caused by candidiasis. Although the binding of griffithsinFrontiers in Cellular and Infection Microbiology 02to the Candida cells is based on the recognition of mannose-containing glycans present on the cell surface, this article addressesthe anti-fungal activity of griffithsin rather than its antiviral activityagainst enveloped viruses.Although the articles of the Research Topic bring new interestinginformation on the antiviral properties of cyanobacterial, algal andplant lectins, it is regrettable that animal lectins and in particular, C-lectins, have not been considered as CBAs for enveloped viruses inthis topic. In this respect, some of the molecules forming the humoralarm of innate immunity recognize various pathogenic envelopedviruses including influenza A virus, HIV-1, Herpes simplex virusand hepatitis C virus (Holmskov et al., 2003). Accordingly, recentresults showed that pentraxin 3 (PTX3) and mannose-binding lectin(MBL) readily anchor to the nucleocapsid and spike proteins ofSARS-CoV-2 and its Omicron VOC, respectively. At nanomolarconcentration, the collectin MBL binds to the SARS-CoV-2 spikeprotein in a glycan-dependent manner and inhibits the infection ofprimary respiratory cells by SARS-CoV-2. Moreover, the bound MBLtriggers the activation of the lectin pathway of complement activation(Stravalaci et al., 2022).Author contributionsAll authors listed have made a substantial, direct, and intellectualcontribution to the work and approved it for publication.Conflict of interestThe authors declare that the research was conducted in theabsence of any commercial or financial relationships that could beconstrued as a potential conflict of interest.Publisher’s noteAll claims expressed in this article are solely those of the authorsand do not necessarily represent those of their affiliatedorganizations, or those of the publisher, the editors and thereviewers. Any product that may be evaluated in this article, orclaim that may be made by its manufacturer, is not guaranteed orendorsed by the publisher.ReferencesBarre, A., Van Damme, E. J. M., Klonjkowski, B., Simplicien, M., Sudor, J., Benoist, H.,et al. (2022). Legume lectins with different specificities as potential glycan probes forpathogenic enveloped viruses. Cells 11, 339. doi: 10.3390/cells11030339Holmskov, U., Thiel, S., and Jensenius, J. C. (2003). Collections and ficolins: humorallectins of the innate immune defense. Annu. Rev. Immunol. 21, 547–578. doi: 10.1146/annurev.immunol.21.120601.140954Stravalaci, M., Pagani, I., Paraboschi, E. M., Pedotti, M., Doni, A., Scavello, F.,et al. (2022). Recognition and inhibition of SARS-CoV-2 by humoral innateimmunity pattern recognition molecules. Nat. Immunol. 23, 275–286. doi:10.1038/s41590-021-01114-wfrontiersin.org

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Editorial: Lectins from plants, algae, fungi, bacteria and animal therapeutic tools for SARS-CoV-2 and other pathogenic enveloped viruses, in a “one-health” perspective

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