Marine Snails and Slugs: a Great Place To Look for Antiviral Drugs

Vinh, Dang; Benkendorff, Kirsten; Green, Timothy J.; Speck, Peter

doi:10.1128/jvi.00287-15

Cited by 50 publications

(55 citation statements)

References 61 publications

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“…Due to their filtering activity, marine bivalves are in contact with a high number of viruses, which commonly reach 10 7 particles per milliliter in the ocean, including putative pathogens (36). Due to this fact, they should have a constitutive "ready-to-use" repertoire of antimicrobial molecules that can act in dangerous situations.…”

Section: Discussionmentioning

confidence: 99%

“…Mollusks have the potential to be a source of antimicrobial and antiviral compounds, but most members of the phylum Mollusca have not yet been examined for the presence of these bioactive molecules (36). Myticins are examples of the biotechnological and therapeutic potential of bivalves, which are currently limited to serving as a food supply, and may represent an added value for their culture.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Antiviral Activity of Myticin C Peptide from Mussel: an Ancient Defense against Herpesviruses

Novoa

Romero

Álvarez

et al. 2016

J Virol

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Little is known about the antiviral response in mollusks. As in other invertebrates, the interferon signaling pathways have not been identified, and in fact, there is a debate about whether invertebrates possess antiviral immunity similar to that of vertebrates. In marine bivalves, due to their filtering activity, interaction with putative pathogens, including viruses, is very high, suggesting that they should have mechanisms to address these infections. In this study, we confirmed that constitutively expressed molecules in naive mussels confer resistance in oysters to ostreid herpesvirus 1 (OsHV-1) when oyster hemocytes are incubated with mussel hemolymph. Using a proteomic approach, myticin C peptides were identified in both mussel hemolymph and hemocytes. Myticins, antimicrobial peptides that have been previously characterized, were constitutively expressed in a fraction of mussel hemocytes and showed antiviral activity against OsHV-1, suggesting that these molecules could be responsible for the antiviral activity of mussel hemolymph. For the first time, a molecule from a bivalve has shown antiviral activity against a virus affecting mollusks. Moreover, myticin C peptides showed antiviral activity against human herpes simplex viruses 1 (HSV-1) and 2 (HSV-2). In summary, our work sheds light on the invertebrate antiviral immune response with the identification of a molecule with potential biotechnological applications. IMPORTANCESeveral bioactive molecules that have potential pharmaceutical or industrial applications have been identified and isolated from marine invertebrates. Myticin C, an antimicrobial peptide from the Mediterranean mussel (Mytilus galloprovincialis) that was identified by proteomic techniques in both mussel hemolymph and hemocytes, showed potential as an antiviral agent against ostreid herpesvirus 1 (OsHV-1), which represents a major threat to the oyster-farming sector. Both hemolymph from mussels and a myticin C peptide inhibited OsHV-1 replication in oyster hemocytes. Additionally, a modified peptide derived from myticin C or the nanoencapsulated normal peptide also showed antiviral activity against the human herpesviruses HSV-1 and HSV-2. Therefore, myticin C is an example of the biotechnological and therapeutic potential of mollusks.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Antiviral Activity of Myticin C Peptide from Mussel: an Ancient Defense against Herpesviruses

Novoa

Romero

Álvarez

et al. 2016

J Virol

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“…During the last decade, hundreds of marine-based bioactive molecules have been discovered with several undergoing clinical trials (Mayer, Rodríguez, Taglialatela-Scafati, & Fusetani, 2013;Suleria, Masci, & Globe, 2015). These bioactive molecules show anti-bacterial, anti-fungal, anti-cancer, anti-viral, as well as anti-inflammatory activities that can be used to promote the health status of humankind (Dang, Benkendorff, Green, & Speck, 2015;Sugiura, Nagayama, Kinoshita, Tanaka, & Matsushita, 2015), however, the biological activity of most of the marine compounds is still unclear and under investigation (Blunt et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

In vitro anti-inflammatory activities of blacklip abalone (Haliotis rubra) in RAW 264.7 macrophages

Suleria

Addepalli

Masci

et al. 2017

Food and Agricultural Immunology

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Abalone (Haliotis sp) has been used as a traditional functional food for many years by different cultures believing that consumption provides health benefits. We investigated the antiinflammatory activity from blacklip abalone visceral waste. An extract was prepared from the viscera using digestion with the food grade proteases papain and bromelain followed by anion exchange chromatography (AEC). The anti-inflammatory potential of the extract and AEC fractions were investigated in comparison to a plant-derived positive control (quercetin) through the inhibition of lipopolysaccharide-stimulated nitric oxide production in RAW 264.7 monocytes. Significant antiinflammatory activity was observed in response to the abalone extract and the unbound AEC material over a concentration (based on collagen) range of 12-96 µg/mL. Overall, results indicated that blacklip abalone extract has anti-inflammatory activity in vitro, warranting further investigation into the bioactive constituents that may be potential anti-inflammatory therapeutics.ARTICLE HISTORY

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“…The hemolymph contains hemocyanin as its major constituent (16). However, endogenous antimicrobial peptides are also present or synthesized and secreted into hemolymph upon microbial challenge (11,(17)(18)(19). Several studies reported that the antiviral activity of hemolymph against HSV-1 is related to hemocyanin (20)(21)(22).…”

mentioning

confidence: 99%

“…Recently, it was shown that hemolymph from molluscs has antiviral activity against herpes simplex virus 1 (HSV-1) (11)(12)(13)(14)(15). The hemolymph contains hemocyanin as its major constituent (16).…”

mentioning

confidence: 99%

Abalone Hemocyanin Blocks the Entry of Herpes Simplex Virus 1 into Cells: a Potential New Antiviral Strategy

Zanjani

Miranda-Saksena

Valtchev

et al. 2016

Antimicrob Agents Chemother

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A marine-derived compound, abalone hemocyanin, from Haliotis rubra was shown to have a unique mechanism of antiviral activity against herpes simplex virus 1 (HSV-1) infections. In vitro assays demonstrated the dose-dependent and inhibitory effect of purified hemocyanin against HSV-1 infection in Vero cells with a 50% effective dose (ED 50 ) of 40 to 50 nM and no significant toxicity. In addition, hemocyanin specifically inhibited viral attachment and entry by binding selectively to the viral surface glycoproteins gD, gB, and gC, probably by mimicking their receptors. However, hemocyanin had no effect on postentry events and did not block infection by binding to cellular receptors for HSV. By the use of different mutants of gD and gB and a competitive heparin binding assay, both protein charge and conformation were shown to be the driving forces of the interaction between hemocyanin and viral glycoproteins. These findings also suggested that hemocyanin may have different motifs for binding to each of the viral glycoproteins B and D. The dimer subunit of hemocyanin with a 10-fold-smaller molecular mass exhibited similar binding to viral surface glycoproteins, showing that the observed inhibition did not require the entire multimer. Therefore, a small hemocyanin analogue could serve as a new antiviral candidate for HSV infections.T he predominant antiviral therapies for herpes simplex virus (HSV) infections are nucleoside analogue inhibitors, such as acyclovir, its prodrug valacyclovir, famciclovir (a prodrug of penciclovir), and the second line of drugs for resistant virus, foscarnet and cidofovir. These drugs are all inhibitors of viral DNA polymerase (1). The variety is limited despite the fact that HSV has more than 80 genes that are required for its functionality and, therefore, could potentially be targeted by multiple types of inhibitors (2). Thus, improving the efficacy of current HSV treatment relies on the discovery of new antiviral compounds targeting various functions of the virus, preferably earlier stages of the HSV viral life cycle such as viral attachment and entry. Viral attachment and entry are regulated by surface glycoproteins gC, gB, gD, and gH-gL (3, 4). Attachment is a two-step process involving the primary interaction of gC and/or gB with heparan sulfate proteoglycans (HSPG), followed by the secondary gD-mediated binding to its receptors, such as herpesvirus entry mediator (HVEM), nectin-1, or 3-O-sulfated heparan sulfate. This interaction triggers the activation of gH-gL and gB, which leads to the fusion of viral envelope and plasma membrane of the host cell either at the surface or in the endosomes (3, 4). Many steps in the entry process of HSV remain unclear; however, it is known that gD determines HSV tropism and that the conformational changes in gD upon binding to its receptors are critical in triggering an activation cascade (5, 6).Viral attachment or entry could be inhibited by mimicking cellular receptors that are involved in these events. For example, heparin interacts with HSPG bi...

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Marine Snails and Slugs: a Great Place To Look for Antiviral Drugs

Cited by 50 publications

References 61 publications

Antiviral Activity of Myticin C Peptide from Mussel: an Ancient Defense against Herpesviruses

Antiviral Activity of Myticin C Peptide from Mussel: an Ancient Defense against Herpesviruses

In vitro anti-inflammatory activities of blacklip abalone (Haliotis rubra) in RAW 264.7 macrophages

Abalone Hemocyanin Blocks the Entry of Herpes Simplex Virus 1 into Cells: a Potential New Antiviral Strategy

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