Abstract
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.
Highlights
Arthropod-borne viruses, mainly described as arboviruses, pose a significant threat to human and animal health in many parts of the world
These data are representative when we consider that the dolastane, which showed the best antiviral potential, is www.nature.com/scientificreports a compound isolated from the C. cervicornis seaweed that displays an interesting anti-Zika virus (ZIKV) and anti-Chikungunya virus (CHIKV) activity, similar to that observed for the other compounds tested, but with high inhibitory potential[24,25,26]
We evaluated the combination of the tested compounds, both the C. cervicornis extract and the isolated dolastane combined with ribavirin, both at low concentrations, i.e., concentrations that were not able to expressively inhibit the replication of ZIKV or CHIKV, inhibiting only up to 20% of viral replication if added separately
Summary
Arthropod-borne viruses, mainly described as arboviruses, pose a significant threat to human and animal health in many parts of the world. The Zika virus (ZIKV), so named in reference to the Ugandan forest, was first isolated in 1947 and is a flavivirus closely related to dengue It was initially recognized as causing an asymptomatic infection or producing a febrile disease in humans and, for decades, did not express major public health concerns[6]. During the outbreak in French Polynesia, it was observed that 42 patients with symptoms of ZIKV infection presented Guillain-Barré syndrome, which represented a considerable increase in the number of cases. These observations had already been related to flavivirus at another time, but not to ZIKV infection. We demonstrated the potential of two dolastanes and a secodolastane isolated from C. cervicornis against HIV-113
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