*4.9. Antiviral E*ff*ects*

Although the research regarding the antiviral potential of algae against food-borne viruses is gaining interest in recent years, currently, the available data are still scarce. The main compounds from algae that have been proved to have antiviral potential are sulphated polysaccharides, including fucoidan, sulphoglycolipids, carrageenan, and sesquiterpene hydroquinone. Marine-derived polysaccharides and their lower molecular weight oligosaccharide derivatives have been shown to possess a variety of antiviral activities and also exert antioxidant and antimicrobial e ffects. In general, algal polysaccharides can suppress the DNA replication and inhibit the host cell colonization by the virus. For example, the antiviral potential of polysaccharides from brown seaweeds revealed a significant inhibiting activity against hepatitis B virus (HBV) DNA polymerase, therefore a ffecting its replication [175]. The antiviral activity of these polysaccharides is exerted through suppression of virus adhesion to the host cells (*U. pinnatifida*, *Cystoseira indica*, *Ascophylum nodosum*) [176]. Fucoindan extract from *Cladosiphon okamurans* was used to inhibit New Castle Disease Virus in vitro in early stages of viral infection (0–60 min post-infection), the compound displaying high selectivity index (IS50 > 2000) for inhibiting syncytia formation [177]. *Grateloupia indica*, *Scinaia hatei*, *Gracilaria* corticata, *Stoechospermum marginatum*, *Cystoseira indica*, and *Caulerpa racemosa* sulfated polysaccharide extracts were screened for antiviral activity against the four serotypes of dengue virus (DENV). DENV-2 was the most susceptible serotype to all polysulfates, with inhibitory concentration 50% values in the range 0.12–20 μg/mL [178]. Krylova et al. [179] found that modified and native fucoidans from marine macroalgae *Fucus evanescens* presented antiviral properties against herpes virus or human immunodeficiency virus. Eom et al. [180] studied the antiviral activity of phlorotannin from *Eisenia bicyclis.* The results showed a strong antiviral potential against norovirus (murine norovirus, MNV) with EC50 of 0.9 μM [180]. Serkedjieva [181] analyzed the influence of *Ceramium rubrum* water extract on the reproduction of a range of influenza viruses in vitro and in ovo. The results showed that the virus-inhibitory e ffect was selective, dose-dependent, and strain-specific. At a concentration over 0.5 mg/mL, the extract also inhibited the reproduction of herpes simplex virus (HSV) type 1 with MIC90 of 1.4 mg/mL.

However, there is still the need for more research to comprehensively understand the antiviral action mechanisms of algae compounds and to benefit from their use as functional ingredients in pharmaceutical and food industries [124].

#### **5. Conclusions and Future Trends**

Nowadays, macroalgae are gaining more interest due to their demonstrated health promoting properties. They can be seen as a valuable source of bioactive compounds that can sustain the human health, preventing or reducing the convalescence period for various diseases, due to their antioxidant, anti-inflammatory, antiproliferative, antiviral, and antibacterial activities.

Although algae have been extensively analyzed regarding their content in biologically active compounds, the potential beneficial and toxicological e ffects on the human body are still of major interest. The identification of compounds directly responsible for the antimicrobial, antiviral, and anticancer activities of algae is still a relatively incipient domain that must be elucidated. Furthermore, the research must be oriented on their use as a substitute for antibiotics through a viable and sustainable approach, this strategy representing progress in solving the major emerging problems related to antibiotic resistance.

A future valorization strategy can be sustained trough an integrated biorefinery concept developed based on cost-e ffective and environmentally-friendly extraction methods. In this context, more research is needed to evaluate nutritional properties and mechanisms underlying the health benefits of a wide variety of macroalgal products.

**Author Contributions:** Conceptualization, E.-S.B.-D. and A.C.F.; methodology, C.R.P. and A.M.R.; investigation, D.M.; writing—original draft preparation, E.-S.B.-D.; writing—review and editing, A.C.F., S.A.S., and O.L.P.; supervision, M.T.; project administration, A.C.F. and S.A.S. All authors have read and agreed to the published version of the manuscript.

**Funding:** The publication was supported by funds from the National Research Development Projects to finance excellence (PFE)-37/2018–2020 granted by the Romanian Ministry of Research and Innovation.

**Acknowledgments:** The work was supported by two grants of the Ministry of Research and Innovation, CNCS-UEFISCDI, project number PN-III-P1–1.1-PD-2016–0869 and PN-III-P1–1.1-TE-2016–0973, within PNCDI III.

**Conflicts of Interest:** The authors declare no conflict of interest.
