Natural Products and Derivatives as Potential Zika virus Inhibitors: A Comprehensive Review

Zika virus (ZIKV) is an arbovirus whose infection in humans can lead to severe outcomes. This article reviews studies reporting the anti-ZIKV activity of natural products (NPs) and derivatives published from 1997 to 2022, which were carried out with NPs obtained from plants (82.4%) or semisynthetic/synthetic derivatives, fungi (3.1%), bacteria (7.6%), animals (1.2%) and marine organisms (1.9%) along with miscellaneous compounds (3.8%). Classes of NPs reported to present antiZIKV activity include polyphenols, triterpenes, alkaloids, and steroids, among others. The highest values of the selectivity index, the ratio between cytotoxicity and antiviral activity (SI = CC50/EC50), were reported for epigallocatechin gallate (SI >= 25,000) and anisomycin (SI >= 11,900) obtained from Streptomyces bacteria, dolastane (SI = 1246) isolated from the marine seaweed Canistrocarpus cervicorni, and the flavonol myricetin (SI >= 862). NPs mostly act at the stages of viral adsorption and internalization in addition to presenting virucidal effect. The data demonstrate the potential of NPs for developing new anti-ZIKV agents and highlight the lack of studies addressing their molecular mechanisms of action and pre-clinical studies of efficacy and safety in animal models. To the best of our knowledge, none of the active compounds has been submitted to clinical studies.

Automated summary

This article reviews studies on the anti-ZIKV activity of natural products (NPs) and derivatives from 1997 to 2022. The majority of the studies used NPs from plants (82.4%) or semisynthetic/synthetic derivatives, followed by fungi (3.1%), bacteria (7.6%), animals (1.2%), and marine organisms (1.9%). Different classes of NPs, such as polyphenols, triterpenes, alkaloids, and steroids, have been reported to exhibit anti-ZIKV activity. NPs mainly act at the stages of viral adsorption and internalization, and some compounds show high selectivity index values. However, further research is needed to understand their mechanisms of action and evaluate their safety and efficacy in animal models.