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Viral Inhibitors Derived from Macroalgae, Microalgae, and Cyanobacteria: A review of antiviral potential throughout pathogenesis

Journal Article · · Algal Research

Viruses are abiotic obligate parasites utilizing complex mechanisms to hijack cellular machinery and reproduce, causing multiple harmful effects in the process. Viruses represent a growing global health concern; at the time of writing, COVID-19 has killed at least two million people around the world and devastated global economies. Lingering concern regarding the virus’ prevalence yet hampers return to normalcy. While catastrophic in and of itself, COVID-19 further heralds in a new era of human-disease interaction characterized by the emergence of novel viruses from natural sources with heretofore unseen frequency. Due to deforestation, population growth, and climate change, we are encountering more viruses that can infect larger groups of people with greater ease and increasingly severe outcomes. The devastation of COVID-19 and forecasts of future human/disease interactions call for a creative reconsideration of global response to infectious disease. There is an urgent need for accessible, cost-effective antiviral (AV) drugs that can be mass-produced and widely distributed to large populations. Development of AV drugs should be informed by a thorough understanding of viral structure and function as well as human biology. To maximize efficacy, minimize cost, and reduce development of drug-resistance, these drugs would ideally operate through a varied set of mechanisms at multiple stages throughout the course of infection. Due to their abundance and diversity, natural compounds are ideal for such comprehensive therapeutic interventions. Promising sources of such drugs are found throughout nature; especially remarkable are the algae, a polyphyletic grouping of phototrophs that produce diverse bioactive compounds. While not much literature has been published on the subject, studies have shown that these compounds exert antiviral effects at different stages of viral pathogenesis. In this review, we follow the course of viral infection in the human body and evaluate the AV effects of algae-derived compounds at each stage. Specifically, we examine the AV activities of algae-derived compounds at the entry of viruses into the body, transport through the body via the lymph and blood, infection of target cells, and immune response. We discuss what is known about algae-derived compounds that may interfere with the infection pathways of SARS-CoV-2; and review which algae are promising sources for AV agents or AV precursors that, with further investigation, may yield life-saving drugs due to their diversity of mechanisms and exceptional pharmaceutical potential.

Research Organization:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Organization:
USDOE
DOE Contract Number:
AC05-76RL01830
OSTI ID:
1784622
Report Number(s):
PNNL-SA-161240
Journal Information:
Algal Research, Vol. 57
Country of Publication:
United States
Language:
English

References (181)

If the world fails to protect the economy, COVID-19 will damage health not just now but also in the future April 2020
Global trends in emerging infectious diseases February 2008
COVID-19: a novel zoonotic disease caused by a coronavirus from China: what we know and what we don't January 2020
Evolution and Emergence of Pathogenic Viruses: Past, Present, and Future January 2017
Urbanization and Disease Emergence: Dynamics at the Wildlife–Livestock–Human Interface January 2017
Risk factors for human disease emergence July 2001
Emerging Infectious Diseases of Wildlife-- Threats to Biodiversity and Human Health January 2000
Livestock infectious diseases and zoonoses September 2009
Climate change and emerging infectious diseases July 2001
Climate Change and Respiratory Infections August 2016
The ecology of Anopheles mosquitoes under climate change: case studies from the effects of deforestation in East African highlands: Ecology of anopheles under climate change February 2012
Why is tick-borne encephalitis increasing? A review of the key factors causing the increasing incidence of human TBE in Sweden August 2012
What Makes Ticks Tick? Climate Change, Ticks, and Tick‐Borne Diseases January 2008
Clinical features and laboratory diagnosis of emerging arthropod-transmitted viruses November 2020
Seasonality and the dynamics of infectious diseases March 2006
Approved Antiviral Drugs over the Past 50 Years June 2016
Antiviral therapy: old and current issues August 2012
Systems biology and combination therapy in the quest for clinical efficacy August 2006
Synergistic antiviral effects against SARS-CoV-2 by plant-based molecules June 2020
Systematic identification of synergistic drug pairs targeting HIV October 2012
Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2 March 2020
Antiviral Natural Products and Herbal Medicines January 2014
The influence of natural products upon drug discovery (Antiquity to late 1999) January 2000
Marine cyanobacteria—a prolific source of natural products November 2001
Bioproducts from Seaweeds: A Review with Special Focus on the Iberian Peninsula May 2014
Microalgae for Biofuels and Animal Feeds November 2013
Carrageenan nasal spray in virus confirmed common cold: individual patient data analysis of two randomized controlled trials January 2014
Efficacy of a Carrageenan nasal spray in patients with common cold: a randomized controlled trial January 2013
Efficacy and safety of an antiviral Iota-Carrageenan nasal spray: a randomized, double-blind, placebo-controlled exploratory study in volunteers with early symptoms of the common cold August 2010
The Intranasal Application of Zanamivir and Carrageenan Is Synergistically Active against Influenza A Virus in the Murine Model June 2015
Inhibition of Influenza A Virus Infection by Fucoidan Targeting Viral Neuraminidase and Cellular EGFR Pathway January 2017
Oral Fucoidan Attenuates Lung Pathology and Clinical Signs in a Severe Influenza A Mouse Model May 2020
The effectiveness of Carraguard, a vaginal microbicide, in protecting women against high-risk human papillomavirus infection January 2011
Efficacy of Carraguard for prevention of HIV infection in women in South Africa: a randomised, double-blind, placebo-controlled trial December 2008
An intravaginal ring that releases three antiviral agents and a contraceptive blocks SHIV-RT infection, reduces HSV-2 shedding, and suppresses hormonal cycling in rhesus macaques June 2017
Algal Lectins as Potential HIV Microbicide Candidates July 2012
In vitro and in vivo anti-herpes simplex virus activity of monogalactosyl diacylglyceride from Coccomyxa sp. KJ (IPOD FERM BP-22254), a green microalga July 2019
Therapeutic efficacy in BALB/C mice of extract from marine alga Canistrocarpus cervicornis (Phaeophyceae) against herpes simplex virus type 1 May 2016
Antiviral Activity of the Marine Alga Symphyocladia latiuscula against Herpes Simplex Virus (HSV-1) in Vitro and Its Therapeutic Efficacy against HSV-1 Infection in Mice January 2005
The inhibitory effects and mechanisms of polymannuroguluronate sulfate against human papillomavirus infection in vitro and in vivo August 2020
Carrageenans: Biological properties, chemical modifications and structural analysis – A review June 2009
Crossing barriers: infections of the lung and the gut December 2008
Inactivation of Enveloped Viruses in Human Bodily Fluids by Purified Lipids May 1994
Diterpenes from the Marine Algae of the Genus Dictyota May 2018
Comparative study on the antiviral activity of selected monoterpenes derived from essential oils: ANTIVIRAL ACTIVITY OF MONOTERPENES DERIVED FROM ESSENTIAL OILS August 2009
The eye as the discrete but defensible portal of coronavirus infection January 2021
Mask use during COVID-19: A risk adjusted strategy November 2020
Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19 December 2020
Geraniin extracted from the rind of Nephelium lappaceum binds to dengue virus type-2 envelope protein and inhibits early stage of virus replication November 2017
Broad-spectrum non-toxic antiviral nanoparticles with a virucidal inhibition mechanism December 2017
Multiple Antiviral Activities in Extracts of Seaweeds from British Columbia January 1999
Drug Therapy in Dental Practice: General Principles: Part 1—Pharmacokinetic Considerations December 2006
Anesthesia for the 21st Century January 2000
Drug Delivery Systems: Entering the Mainstream March 2004
Antiviral activity of 7-keto-stigmasterol obtained from green Antarctic algae Prasiola crispa against equine herpesvirus 1 September 2016
Anti-HIV / HCV Activity of Cyanobacterial Phycobiliproteins by a New Standardized Method Using Bacteriophage Surrogates October 2019
Discovery of cyanovirin-N, a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycoprotein gp120: potential applications to microbicide development. July 1997
Middle East respiratory syndrome coronavirus infection is inhibited by griffithsin September 2016
In vitro inhibitory effect of carrageenan oligosaccharide on influenza A H1N1 virus November 2011
The Comparative Analysis of Antiviral Activity of Native and Modified Fucoidans from Brown Algae Fucus evanescens In Vitro and In Vivo April 2020
Antiviral Activity against Avian Leucosis Virus Subgroup J of Degraded Polysaccharides from Ulva pertusa August 2018
Additionally sulfated xylomannan sulfates from Scinaia hatei and their antiviral activities October 2015
Immunomodulatory and Anti-IBDV Activities of the Polysaccharide AEX from Coccomyxa gloeobotrydiformis February 2017
Loliolide in marine algae March 2009
Virucidal and Synergistic Activity of Polyphenol-Rich Extracts of Seaweeds against Measles Virus August 2018
In vitro Studies on The Inhibition of Replication of Zika and Chikungunya Viruses by Dolastane Isolated from Seaweed Canistrocarpus cervicornis May 2020
In vitro bioavailability of chlorophyll pigments from edible seaweeds February 2018
DAG tales: the multiple faces of diacylglycerol—stereochemistry, metabolism, and signaling July 2015
Effects of triacylglycerol and diacylglycerol oils on blood clearance, tissue uptake, and hepatic apolipoprotein B secretion in mice May 2007
Controversial role of plant sterol esters in the management of hypercholesterolaemia September 2008
Phytosterols, Lipid Administration, and Liver Disease During Parenteral Nutrition July 2015
Loliolide, a Carotenoid Metabolite, Is a Potential Endogenous Inducer of Herbivore Resistance January 2019
New Loliolide Derivatives from the Brown Alga Undaria pinnatifida January 2002
Loliolide - the most ubiquitous lactone December 2015
The lectin–cell interaction and its implications to intestinal lectin-mediated drug delivery March 2004
Investigation of lectin-modified insulin liposomes as carriers for oral administration April 2005
Improving Efficacy, Oral Bioavailability, and Delivery of Paclitaxel Using Protein-Grafted Solid Lipid Nanoparticles October 2016
In vitro antiviral activity of phlorotannins isolated from Ecklonia cava against porcine epidemic diarrhea coronavirus infection and hemagglutination August 2013
Polyphenols: food sources and bioavailability May 2004
Hepatoprotective Effect of C-Phycocyanin: Protection for Carbon Tetrachloride andR-(+)-Pulegone-Mediated Hepatotoxicty in Rats August 1998
Effect of phycocyanin in zymosan-induced arthritis in mice?phycocyanin as an antiarthritic compound October 1999
The Antiviral Activities and Mechanisms of Marine Polysaccharides: An Overview December 2012
Herpes simplex virus type 1 variants arising after selection with an antiviral carrageenan: Lack of correlation between drug susceptibility and syn phenotype July 2002
Antiviral Activity of a Carrageenan from Gigartina skottsbergii against Intraperitoneal Murine Herpes simplex Virus Infection November 2006
Inhibitory Effects of Laminaria japonica Fucoidans Against Noroviruses September 2020
Structural characterization and antiviral activity of two fucoidans from the brown algae Sargassum henslowianum February 2020
Sulfated polysaccharides effectively inhibit SARS-CoV-2 in vitro July 2020
Sulphated Polysaccharides from Ulva clathrata and Cladosiphon okamuranus Seaweeds both Inhibit Viral Attachment/Entry and Cell-Cell Fusion, in NDV Infection January 2015
Immune Activation of RAW264.7 Macrophages by Low Molecular Weight Fucoidan Extracted from New Zealand Undaria pinnatifida September 2018
Neutrophils in viral infections: Current concepts and caveats July 2015
Structural characteristics and in vitro macrophage activation of acetyl fucoidan from Cladosiphon okamuranus February 2009
Stimulation of turbot phagocytes by Ulva rigida C. Agardh polysaccharides April 2006
The immunomodulatory effect of LPS, laminaran and sulphated laminaran [beta(l,3)-D-glucan] on Atlantic salmon, Salmo salar L., macrophages in vitro March 1995
Effects of κ-Carrageenan on the Non-Specific Defense System of Carp Cyprinus carpio January 1997
Carrageenan Primes Leukocytes To Enhance Lipopolysaccharide-Induced Tumor Necrosis Factor Alpha Production July 1999
Biocompatibility of Wound Management Products: A Study of the Effects of Various Polysaccharides on Murine L929 Fibroblast Proliferation and Macrophage Respiratory Burst June 1993
Antiviral efficacy of orally delivered neoagarohexaose, a nonconventional TLR4 agonist, against norovirus infection in mice December 2020
Activation of Murine Macrophages by Polysaccharide Fractions from Marine Algae ( Porphyra yezoensis ) January 1993
Macrophage Stimulation Activity of the Polysaccharide Fraction from a Marine Alga ( Porphyra yezoensis ): Structure-Function Relationships and Improved Solubility January 1995
Fucoidan Isolated from Laminaria angustata var. longissima Induced Macrophage Activation September 2010
Immunomodulating Activity of Arabinogalactan and Fucoidan In Vitro December 2005
Synthesis and immunomodulatory activity of the sulfated tetrasaccharide motif of type B ulvanobiuronic acid 3-sulfate January 2020
Immunomodulatory effect of dietary Saccharomyces cerevisiae, β-glucan and laminaran in mercuric chloride treated Nile tilapia (Oreochromis niloticus) and experimentally infected with Aeromonas hydrophila May 2010
Carrageenans as Broad-Spectrum Microbicides: Current Status and Challenges August 2020
Palmitic Acid Is a Novel CD4 Fusion Inhibitor That Blocks HIV Entry and Infection December 2009
Isolation, chemical investigation and antiviral activity of polysaccharides from Gracilaria corticata (Gracilariaceae, Rhodophyta) December 2002
Calcium Spirulan, an Inhibitor of Enveloped Virus Replication, from a Blue-Green Alga Spirulina platensis January 1996
Effects of Structural Modification of Calcium Spirulan, a Sulfated Polysaccharide from Spirulina Platensis, on Antiviral Activity. January 2001
Anti-herpes Simplex Virus Target of an Acidic Polysaccharide, Nostoflan, from the Edible Blue-Green Alga Nostoc flagelliforme January 2007
Pressurized Liquid Extraction as an Alternative Process To Obtain Antiviral Agents from the Edible Microalga Chlorella vulgaris August 2010
Antiviral compounds obtained from microalgae commonly used as carotenoid sources May 2011
A Natural Sulfated Polysaccharide, Calcium Spirulan, Isolated from Spirulina platensis: In Vitro and ex Vivo Evaluation of Anti-Herpes Simplex Virus and Anti-Human Immunodeficiency Virus Activities October 1996
Sulfated polymannuroguluronate, a novel anti-acquired immune deficiency syndrome (AIDS) drug candidate, targeting CD4 in lymphocytes August 2004
The potential molecular targets of marine sulfated polymannuroguluronate interfering with HIV-1 entryInteraction between SPMG and HIV-1 rgp120 and CD4 molecule July 2003
Antiviral activity against enterovirus 71 of sulfated rhamnan isolated from the green alga Monostroma latissimum November 2018
A sulfated glucuronorhamnan from the green seaweed Monostroma nitidum: Characteristics of its structure and antiviral activity January 2020
Sulfated polymannuroguluronate, a novel anti-AIDS drug candidate, inhibits HIV-1 Tat-induced angiogenesis in Kaposi's sarcoma cells November 2007
HIV: Cell Binding and Entry April 2012
A comprehensive pathway map of epidermal growth factor receptor signaling January 2005
The Epidermal Growth Factor Receptor (EGFR) Promotes Uptake of Influenza A Viruses (IAV) into Host Cells September 2010
Proteins and Carbohydrates from Red Seaweeds: Evidence for Beneficial Effects on Gut Function and Microbiota August 2015
Structure and anti-dengue virus activity of sulfated polysaccharide from a marine alga November 2008
Interference in dengue virus adsorption and uncoating by carrageenans July 2007
The antiviral activity of sulfated polysaccharides against dengue virus is dependent on virus serotype and host cell June 2005
Anti-Chikungunya Viral Activities of Aplysiatoxin-Related Compounds from the Marine Cyanobacterium Trichodesmium erythraeum January 2014
Dolastatin 3 and Two Novel Cyclic Peptides from a Palauan Collection of Lyngbya m ajuscula February 2000
Inhibition of HIV-1 Reverse Transcriptase and Protease by Phlorotannins from the Brown Alga Ecklonia cava January 2004
Inhibitory activity on HIV-1 reverse transcriptase and integrase of a carmalol derivative from a brown Alga,Ishige okamurae January 2006
Overview on the antiviral activities and mechanisms of marine polysaccharides from seaweeds December 2017
Antiviral Potential of Algae Polysaccharides Isolated from Marine Sources: A Review January 2015
Purification and characterization of an avian myeloblastosis and human immunodeficiency virus reverse transcriptase inhibitor, sulfated polysaccharides extracted from sea algae. October 1987
Sulfoquinovosyldiacylglycerol, KM043, a New Potent Inhibitor of Eukaryotic DNA Polymerases and HIV-Reverse Transcriptase Type 1 from a Marine Red Alga, Gigartina tenella. January 1998
Inhibition of Reverse Transcriptase Activity by Extracts of Cultured Blue-Green Algae (Cyanophyta) April 1993
Use of microalgae Chlamydomonas reinhardtii for production of double-stranded RNA against shrimp virus May 2016
Advances in algal drug research with emphasis on enzyme inhibitors December 2014
Evaluation of HIV-1 inhibition by stereoisomers and analogues of the sesquiterpenoid hydroquinone peyssonol A April 2013
The hepatitis B virus October 1985
The Potential of Algal Biotechnology to Produce Antiviral Compounds and Biopharmaceuticals September 2020
Dieckol, a SARS-CoV 3CLpro inhibitor, isolated from the edible brown algae Ecklonia cava July 2013
Cyclic Depsipeptides, Ichthyopeptins A and B, from Microcystis ichthyoblabe July 2007
Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and plant-derived phenolic compounds October 2005
Sterols in red algae (Rhodophyceae)1 April 1968
SARS-CoV 3CL protease cleaves its C-terminal autoprocessing site by novel subsite cooperativity October 2016
Lead- and drug-like compounds: the rule-of-five revolution December 2004
ADMET—turning chemicals into drugs August 2001
Results of a Large Scale Screen of Microalgae for the Production of Protease Inhibitors February 1988
Mechanisms of Viral Membrane Fusion and Its Inhibition June 2001
Influenza Virus Neuraminidase Inhibitory Activity of Phlorotannins from the Edible Brown Alga Ecklonia cava June 2011
Cyanovirin-N potently inhibits human immunodeficiency virus type 1 infection in cellular and cervical explant models January 2009
Microvirin, a Novel α(1,2)-Mannose-specific Lectin Isolated from Microcystis aeruginosa, Has Anti-HIV-1 Activity Comparable with That of Cyanovirin-N but a Much Higher Safety Profile August 2010
Influenza Neuraminidase: A Neglected Protein and Its Potential for a Better Influenza Vaccine July 2020
Roles of neuraminidase in the initial stage of influenza virus infection April 2006
Myristoylation as a target for inhibiting HIV assembly: Unsaturated fatty acids block viral budding September 2002
Antimycobacterial Activity of the Red Alga Polysiphonia virgata . January 2008
Interference with HIV-induced syncytium formation and viral infectivity by inhibitors of trimming glucosidase November 1987
Inhibition of HIV-1 Replication by an Aqueous Extract of Spirulina platensis (Arthrospira platensis) January 1998
Micro RNA Expression after Ingestion of Fucoidan; A Clinical Study February 2020
Sulfated glycans induce rapid hematopoietic progenitor cell mobilization: evidence for selectin-dependent and independent mechanisms October 2000
Fucoidan from sea cucumber Holothuria polii: Structural elucidation and stimulation of hematopoietic activity July 2020
Therapeutic effects of an orally administered edible seaweed-derived polysaccharide preparation, ascophyllan HS, on a Streptococcus pneumoniae infection mouse model July 2020
Ascophyllan Purified from Ascophyllum nodosum Induces Th1 and Tc1 Immune Responses by Promoting Dendritic Cell Maturation July 2014
The potent activity of sulfated polysaccharide, ascophyllan, isolated from Ascophyllum nodosum to induce nitric oxide and cytokine production from mouse macrophage RAW264.7 cells: Comparison between ascophyllan and fucoidan November 2011
Oral administration of a Spirulina extract enriched for Braun-type lipoproteins protects mice against influenza A (H1N1) virus infection February 2015
Immolina, a High–Molecular-Weight Polysaccharide Fraction of Spirulina, Enhances Chemokine Expression in Human Monocytic THP-1 Cells June 2006
Oral administration of Euglena gracilis Z and its carbohydrate storage substance provides survival protection against influenza virus infection in mice December 2017
Nanoparticles assembled from fucoidan and trimethylchitosan as anthrax vaccine adjuvant: In vitro and in vivo efficacy in comparison to CpG May 2020
Nitric oxide and virus infection: NO and virus infection November 2000
MHC Class I Molecules Exacerbate Viral Infection by Disrupting Type I Interferon Signaling September 2019
Marine Algal Antioxidants as Potential Vectors for Controlling Viral Diseases May 2020
Oxidative stress influences positive strand RNA virus genome synthesis and capping January 2015
Challenges at the Time of COVID-19: Opportunities and Innovations in Antivirals from Nature May 2020
Antiviral and Antioxidant Properties of Echinochrome A December 2018
Antioxidant Therapy as a Potential Approach to Severe Influenza-Associated Complications February 2011
Inhibitory effect of diphlorethohydroxycarmalol on melanogenesis and its protective effect against UV-B radiation-induced cell damage May 2010
Evaluation of diphlorethohydroxycarmalol isolated from Ishige okamurae for radical scavenging activity and its protective effect against H2O2-induced cell damage April 2009
Antioxidant role of astaxanthin in the green alga Haematococcus pluvialis September 1997
The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus February 2020
Remdesivir for the Treatment of Covid-19 — Final Report November 2020
Man-Specific, GalNAc/T/Tn-Specific and Neu5Ac-Specific Seaweed Lectins as Glycan Probes for the SARS-CoV-2 (COVID-19) Coronavirus October 2020
The structure-activity relationship of the interactions of SARS-CoV-2 spike glycoproteins with glucuronomannan and sulfated galactofucan from Saccharina japonica November 2020
COVID-19: consider cytokine storm syndromes and immunosuppression March 2020

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