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      Antiviral Potential of Algal Metabolites—A Comprehensive Review

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          Abstract

          Historically, algae have stimulated significant economic interest particularly as a source of fertilizers, feeds, foods and pharmaceutical precursors. However, there is increasing interest in exploiting algal diversity for their antiviral potential. Here, we present an overview of 50-years of scientific and technological developments in the field of algae antivirals. After bibliometric analysis of 999 scientific references, a survey of 16 clinical trials and analysis of 84 patents, it was possible to identify the dominant algae, molecules and viruses that have been shaping and driving this promising field of research. A description of the most promising discoveries is presented according to molecule class. We observed a diverse range of algae and respective molecules displaying significant antiviral effects against an equally diverse range of viruses. Some natural algae molecules, like carrageenan, cyanovirin or griffithsin, are now considered prime reference molecules for their outstanding antiviral capacity. Crucially, while many algae antiviral applications have already reached successful commercialization, the large spectrum of algae antiviral capacities already identified suggests a strong potential for future expansion of this field.

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          Most cited references173

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          World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19)

          An unprecedented outbreak of pneumonia of unknown aetiology in Wuhan City, Hubei province in China emerged in December 2019. A novel coronavirus was identified as the causative agent and was subsequently termed COVID-19 by the World Health Organization (WHO). Considered a relative of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), COVID-19 is caused by a betacoronavirus named SARS-CoV-2 that affects the lower respiratory tract and manifests as pneumonia in humans. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 continues to rise, with 90,870 laboratory-confirmed cases and over 3,000 deaths worldwide. In response to this global outbreak, we summarise the current state of knowledge surrounding COVID-19.
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            Ebola virus disease

            Ebola virus disease (EVD) is a severe and frequently lethal disease caused by Ebola virus (EBOV). EVD outbreaks typically start from a single case of probable zoonotic transmission, followed by human-to-human transmission via direct contact or contact with infected bodily fluids or contaminated fomites. EVD has a high case–fatality rate; it is characterized by fever, gastrointestinal signs and multiple organ dysfunction syndrome. Diagnosis requires a combination of case definition and laboratory tests, typically real-time reverse transcription PCR to detect viral RNA or rapid diagnostic tests based on immunoassays to detect EBOV antigens. Recent advances in medical countermeasure research resulted in the recent approval of an EBOV-targeted vaccine by European and US regulatory agencies. The results of a randomized clinical trial of investigational therapeutics for EVD demonstrated survival benefits from two monoclonal antibody products targeting the EBOV membrane glycoprotein. New observations emerging from the unprecedented 2013–2016 Western African EVD outbreak (the largest in history) and the ongoing EVD outbreak in the Democratic Republic of the Congo have substantially improved the understanding of EVD and viral persistence in survivors of EVD, resulting in new strategies toward prevention of infection and optimization of clinical management, acute illness outcomes and attendance to the clinical care needs of patients.
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              Isolation and characterization of griffithsin, a novel HIV-inactivating protein, from the red alga Griffithsia sp.

              Griffithsin (GRFT), a novel anti-HIV protein, was isolated from an aqueous extract of the red alga Griffithsia sp. The 121-amino acid sequence of GRFT has been determined, and biologically active GRFT was subsequently produced by expression of a corresponding DNA sequence in Escherichia coli. Both native and recombinant GRFT displayed potent antiviral activity against laboratory strains and primary isolates of T- and M- tropic HIV-1 with EC50 values ranging from 0.043 to 0.63 nM. GRFT also aborted cell-to-cell fusion and transmission of HIV-1 infection at similar concentrations. High concentrations (e.g. 783 nM) of GRFT were not lethal to any tested host cell types. GRFT blocked CD4-dependent glycoprotein (gp) 120 binding to receptor-expressing cells and bound to viral coat glycoproteins (gp120, gp41, and gp160) in a glycosylation-dependent manner. GRFT preferentially inhibited gp120 binding of the monoclonal antibody (mAb) 2G12, which recognizes a carbohydrate-dependent motif, and the (mAb) 48d, which binds to CD4-induced epitope. In addition, GRFT moderately interfered with the binding of gp120 to sCD4. Further data showed that the binding of GRFT to soluble gp120 was inhibited by the monosaccharides glucose, mannose, and N-acetylglucosamine but not by galactose, xylose, fucose, N-acetylgalactosamine, or sialic acid-containing glycoproteins. Taken together these data suggest that GRFT is a new type of lectin that binds to various viral glycoproteins in a monosaccharide-dependent manner. GRFT could be a potential candidate microbicide to prevent the sexual transmission of HIV and AIDS.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Mar Drugs
                Mar Drugs
                marinedrugs
                Marine Drugs
                MDPI
                1660-3397
                06 February 2021
                February 2021
                : 19
                : 2
                : 94
                Affiliations
                [1 ]Edificio TecLabs, Faculdade de Ciências, Biosystems and Integrative Sciences Institute (BioISI), Universidade de Lisboa, Campus da FCUL, Campo Grande, 1749-016 Lisboa, Portugal
                [2 ]Algae for Future, SA, Rua Eng. Clément Dumoulin Business Park, 2625-106 Póvoa de Santa Iria, Portugal; vitor.verdelho@ 123456gmail.com
                [3 ]Institute of Biochemistry, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany; ramos.anasofiaferreira@ 123456gmail.com
                [4 ]NORCE Norwegian Research Centre, Postboks 22 Nygårdstangen, 5838 Bergen, Norway; papu@ 123456norceresearch.no
                [5 ]Plymouth Marine Laboratory, Plymouth PL1 3DH, UK; mija@ 123456pml.ac.uk
                [6 ]College of Life and Environmental Sciences, University of Exeter, Exeter EX4 4QD, UK
                [7 ]European Algae Biomass Association, Viale Belfiore, 10-50144 Florence, Italy
                Author notes
                [* ]Correspondence: pagarete@ 123456gmail.com ; Tel.: +47-4744-2063
                Author information
                https://orcid.org/0000-0003-1347-0282
                https://orcid.org/0000-0003-0093-7816
                https://orcid.org/0000-0001-8504-7171
                Article
                marinedrugs-19-00094
                10.3390/md19020094
                7914423
                33562153
                9658711a-0688-479b-acbf-0036ba882fb6
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 02 December 2020
                : 02 February 2021
                Categories
                Review

                Pharmacology & Pharmaceutical medicine
                algae,cyanobacteria,immunomodulatory effects,sulfated polysaccharides,lectins,hiv,coronaviruses

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