According to an article published in the journal Reviews in Medical Virology, the effectiveness of mollusc-derived antiviral agents has been proven in many different laboratory and animal studies, while its efficacy against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has also been proposed by recent in silico studies.
Since the start of the coronavirus disease 2019 (COVID-19) pandemic, several different SARS-CoV-2 variants of concern (including the most recent and pervasive delta strain) have emerged with notable changes in viral epidemiology and transmissibility.
Naturally, this threatens the efficacy of vaccines that we have on our disposal, but also antiviral drugs that are currently in clinical trials or on the brink of approval. Hence, while the science community continues to tackle this moving target, ongoing work on identifying novel antiviral compounds against SARS-CoV-2 is pivotal and should not stop.
Unexplored potential of marine invertebrates
One of the realistic possibilities are marine invertebrates that represent an unexploited source of medicinal compounds. More specifically, marine organisms of the phylum Mollusca have miraculous innate immunity, which also entails the production of powerful antiviral compounds.
The only antiviral drug derived from marine invertebrates that is currently available on the market is known as vidarabine; however, this compound subsequently inspired the design of acyclovir (drug that we used against herpesviruses) and zidovudine (one of the first drugs used in the treatment of HIV-infection).
The success of these drugs thus exemplifies how marine invertebrates are not only a direct source of antiviral compounds but can also inspire the synthesis of entirely new ones. And taking into account the fact that there are approximately 100,000 species in the aforementioned phylum, we barely scratched the surface on the opportunity here.
Molluscs that can inhibit viruses
Still, despite the proven activity of many mollusc-derived antivirals in vitro (which includes human viruses), as well as their diverse mechanisms of action, they were not used clinically yet. One of the reasons is that their modes of action are not entirely elucidated.
However, we know that the lipophilic digestive gland extract and the circulatory fluid of greenlip abalone (Haliotis laevigata) can inhibit the entry or hamper early intracellular stage of the infection with the herpes simplex virus type 1 in Vero cells (i.e., kidney epithelial cells extracted from an African green monkey).
The inhibition of herpes simplex virus type 1 has also been seen in vitro with the extracts from the European flat oyster (Ostrea edulis), common cockle (Cerastoderma edule), the common whelk (Buccinum undatum), Japanese carpet shell (Ruditapes philippinarum), blacklip abalone (Haliotis rubra), the Mediterranean mussel (Mytilus galloprovincialis) and veined rapa whelk (Rapanosa venosa).
Rapanosa venosa. Image Credit: Tana Dan84
The antiviral activity of certain molluscs also extends to other herpesviruses (such as Epstein-Barr virus), while oyster hemolymph also harbors compounds active against infectious pancreatic necrosis virus and human adenovirus type 5.
We know that intracellular zinc shows high inhibitory activity against various coronaviral enzymes – most notably 3C-like and papain-like proteases and RNA-dependent RNA polymerase pivotal for viral replication. Therefore, zinc has the propensity to act as a therapeutic agent for SARS-CoV-2, which can be improved by coupling with a metal chaperone.
As the Pacific oyster (Crassostrea gigas) has a high zinc content and also contains cavortin (its major hemolymph protein) as a metal chaperone, it is indeed possible that there is a potential antiviral activity against SARS-CoV-2. Furthermore, it may also act as a metal chaperone which enables the movement of zinc into host cells.
Nonetheless, the specific mechanism behind cavortin’s antiviral activity is still unknown, and there is also a question of its bioavailability in cell culture and animal models. However, the unexplored potential for a new antiviral compound against SARS-CoV-2 is definitely tempting.
Finally, there is a problem of a stringent biosafety level for laboratories working with SARS-CoV-2. However, during the initial screening endeavors, common cold coronaviruses can be used in order to screen compounds with potential universal action. In any case, the remarkable diversity of molluscs may again play in our favor.