Viral inhibitors derived from macroalgae, microalgae, and cyanobacteria: A review of antiviral potential throughout pathogenesis

Abstract

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.

Promising Antiviral Activities of Natural Flavonoids against SARS-CoV-2 Targets: Systematic Review

“…While in silico approaches such as molecular dynamics and structure-based virtual screening represent some of the early steps of drug discovery, in vitro studies utilize the findings to narrow down further and experiment with the most promising compounds in cell-based or cell-free methodologies. Flavonoids represent potential candidates to interfere with the coronavirus life cycle because of their safe administration with lack of systemic toxicity, their ability to work in synergy even with other drugs, and the capacity of their functional groups to interact with different cellular targets and intercept multiple pathways [24,25]. Flavonoids as natural substances represent potential candidates against the actual pandemic because of their biological availability and the participation of most countries (194 countries) on national-level policy for herbal medicines [26].…”

Antiviral Activities of Algal-Based Sulfated Polysaccharides

“…The mechanisms were observed by the decrease in IC 50 on the addition of fucoidan after 1 h of virus infection by 14, 5.1, and 55 µg/mL IC 50 against HSV-1, HSV-2, and influenza A virus, respectively (Table 4) [95]. Furthermore, Song et al reported that ι-carrageenan inhibited only 50-60% SARS-CoV-2 infection on Vero E6 Cells at ≥125 µg/mL [86,89]. Sulfated polysaccharides isolated from sea cucumber Stichopus japonicus (SCSP), which is mainly composed of fucosylated chondroitin sulfate and fucoidan, had an IC 50 of 9.10 µg/mL, and fucoidan itself inhibited 60% of viral infection at ≥15.6 µg/mL.…”

“…A few algal-based sulfated polysaccharides are already well-known for their application as food additives and in the cosmeceutical industry by utilizing their antioxidative, anti-inflammatory, and anticoagulative properties, along with their potency to inhibit adipogenesis [23,63,83]. As a result of their multiple biological activities and their safety, they have gained attention as an antiviral agent [84][85][86]. In particular, such attention is driven by the urge to obtain a suitable agent to prevent further casualties of respiratory infection caused by the SARS-CoV-2 strain and to protect against new and re-emerging viruses [87].…”

Antiviral Strategies Using Natural Source-Derived Sulfated Polysaccharides in the Light of the COVID-19 Pandemic and Major Human Pathogenic Viruses

“…Seaweeds, including brown (Phaeophyceae), green (Chlorophyta), and red (Rhodophyta), biosynthesize various sulfated polysaccharides as a key component of their cell walls [116][117][118][119]. The structures of these polymers vary greatly, and many of them exhibited a wide spectrum of antiviral activity [29,31,67,120,121]. The following section will explore a number of promising naturally occurring sulfated polysaccharides analysing the antiviral activity of these polymers.…”

“…The results obtained demonstrated that direct local administration of ι-carrageenan with nasal sprays significantly reduced the duration of RV-associated cold symptoms. Carrageenan binds to viral glycoproteins, forming a physical barrier that prevents virions from infecting their target cells [121]. Fewer viruses were able to reproduce as limited viruses have access to epithelial tissue, resulting in lower viral titers and faster symptom relief.…”