Natural products isolated from seaweeds have shown great antiviral potential against numerous viruses such as human type 1 herpes, human immunodeficiency virus, and dengue. Diterpenes produced by the brown seaweeds Dictyota and Canistrocarpus, in particular, have shown antiviral or virucidal activity. Recently, the Zika virus (ZIKV) has become a major public health concern due to its widespread dissemination throughout the Americas. Since no vaccines are available, and no drugs have effectively treated recent cases of infection, our group evaluated products from Dictyota menstrualis for their antiviral potential, alone and in combination with Ribavirin. We first evaluated the compounds’ cytotoxicity at high concentrations, and then evaluated the inhibition of ZIKV replication by crude extracts and acetylated crude extracts and their fractions at 20 μg/mL. The F-6 and FAc-2 fractions, rich in cyclic diterpenes with aldehyde groupings, inhibited ZIKV replication by >74%, with inhibition behaving in a dose-dependent manner and the 50% effective concentration (EC50) values of 2.80 (F-6) and 0.81 (FAc-2) μg/mL. Regarding the mechanism of action, FAc-2 had strong virucidal potential, and F-6 inhibited viral adsorption. Associating FAc-2 with Ribavirin at suboptimal dosages produced a strong synergistic effect that completely inhibited viral replication. Our results indicate that these natural products have excellent inhibitory potential against ZIKV replication and may be promising for developing affective therapies.

The discovery of new substances that present innumerable biological activities for the development of drugs is increasingly difficult. Natural marine products are a source of substances with a diversified chemical structure, a broad spectrum of biological activities and low cytotoxicity, which are the essential characteristics for the development of a new drug. An increasing number of reports of Chikungunya virus (CHIKV) infections, in addition to the lack of specific antiviral therapy or vaccines, emphasizes the importance of searching for effective therapy. Studies with the marine green alga Caulerpa racemosa showed antiviral potential. Hence, the aim of this work was to evaluate the anti-CHIKV activity of a marine alkaloid isolated from green alga C. racemosa. Vero cells were used in antiviral assays, submitted to CHIKV, and treated with different concentrations of caulerpin. In the antiviral activity, we observed that the isolated compound showed a much significant and promising EC50 inhibitory effect of 0.8 µM. When evaluating the virucidal activity, we observed that caulerpin was very efficient against CHIKV, being able to inhibit around 90% of the viral infectivity when treated with 5 μM of the compound. We observed that caulerpin added at times 0, 1, 2, and 3 postinfection still maintains a 100% inhibitory potential of viral replication for CHIKV. These studies suggest that the said compounds might be potentially studied for use in the prevention and treatment of CHIKV infections. Derivatives can be considered as a promising new anti-CHIKV drug and can be used for clinical testing.

Chikungunya virus (CHIKV) infection is one of the most challenging re-emergent diseases caused by a virus, and with no specific antiviral treatment it has now become a major public health concern. In this investigation, 25 blood samples were collected from patients with characteristic CHIKV symptoms and submitted to a virus isolation protocol, which detected 3 CHIKV isolates. These samples were evaluated by sequencing for the characterization of the strains and any homology to viruses circulating in Brazil during a recent outbreak. These viruses were used for the development of antiviral assays. Subsequently, the inhibitory effects of seaweed extracts on CHIKV replication were studied. The marine species of algae tested were Bryothamnion triquetrum, Caulerpa racemosa, Laurencia dendroidea, Osmundaria obtusiloba, Ulva fasciata, and Kappaphycus alvarezii, all of which are found in different countries including Brazil. The results revealed high levels of CHIKV inhibition, including extracts of O. obtusiloba with inhibition values of 1.25 μg/mL and a selectivity index of 420. Viral inhibition was dependent on the time of addition of extract of O. obtusiloba to the infected cells, with the optimal inhibition occurring up to 16 h after infection. Neuron evaluations with O. obtusiloba were performed and demonstrated low toxicity, and in infected neurons we observed high inhibitory activity in a dose-dependent manner. These results indicate that the algal extracts may be promising novel candidates for the development of therapeutic agents against CHIKV infections.

The lack of vaccines and antiviral treatment, along with the increasing number of cases of Zika virus (ZIKV) and Chikungunya virus (CHIKV) infections, emphasize the need for searching for new therapeutic strategies. In this context, the marine brown seaweed Canistrocarpus cervicornis has been proved to hold great antiviral potential. Hence, the aim of this work was to evaluate the anti-ZIKV and anti-CHIKV activity of a marine dolastane isolated from brown seaweed C. cervicornis and its crude extract. Vero cells were used in antiviral assays, submitted to ZIKV and CHIKV, and treated with different concentrations of C. cervicornis extract or dolastane. The crude extract of C. cervicornis showed inhibitory activities for both ZIKV and CHIKV, with EC50 values of 3.3 μg/mL and 3.1 μg/mL, respectively. However, the isolated dolastane showed a more significant and promising inhibitory effect (EC50 = 0.95 µM for ZIKV and 1.3 µM for CHIKV) when compared to both the crude extract and ribavirin, which was used as control. Also, the dolastane showed a very potent virucidal activity against CHIKV and was able to inhibit around 90% of the virus infectivity at 10 μM. For the ZIKV, the effects were somewhat lower, although interesting, at approximately 64% in this same concentration. Further, we observed that both the extract and the dolastane were able to inhibit the replication of ZIKV and CHIKV at different times of addition post-infection, remaining efficient even if added after 8 hours post-infection, but declining soon after. A synergistic effect using sub-doses of the extract and isolates was associated with ribavirin, inhibiting above 80% replication even at the lowest concentrations. Therefore, this work has unveiled the anti-ZIKV and CHIKV potential of C. cervicornis crude extract and an isolated dolastane, which, in turn, can be used as a preventive or therapeutic strategy in the future.

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