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 anti-ZIKV 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.

RESUMO As plantas produzem uma grande variedade de metabólitos secundários que frequentemente são relacionados a mecanismos de proteção da planta contra predadores e patógenos. As espécies tóxicas são aquelas capazes de produzirem compostos que podem causar alterações metabólicas prejudiciais ao homem e aos animais. A toxicidade apresentada por uma espécie vegetal pode estar relacionada a fatores associados ao indivíduo, à planta, ao modo de exposição e a questões ambientais. A intoxicação, aguda ou crônica, causada por plantas é difícil de ser diagnosticada assim como a associação entre os sintomas e o consumo e/ou contato com algumas espécies é difícil de ser estabelecida. No âmbito da saúde pública, as intoxicações causadas por plantas possuem impacto expressivo. No Brasil foram registrados 1026 casos em 2012, sendo que a maior parte deles ocorreu com crianças de 0 a 4 anos, de acordo com os dados do SINITOX. O objetivo deste trabalho foi realizar um levantamento bibliográfico de espécies vegetais, brasileiras e exóticas aclimatadas, citadas como tóxicas apesar de serem utilizadas com fins ornamentais e medicinais.

This paper reports the in silico prediction of biological activities of lignans from Diphylleia cymosa and Podophyllum hexandrum combined with an in vitro bioassays. The extracts from the leaves, roots and rhizomes of both species were evaluated for their antibacterial, anticholinesterasic, antioxidant and cytotoxic activities. A group of 27 lignans was selected for biological activities prediction using the Active-IT system with 1987 ligand-based bioactivity models. The in silico approach was properly validated and several ethnopharmacological uses and known biological activities were confirmed, whilst others should be investigated for new drugs with potential clinical use. The extracts from roots of D. cymosa and from rhizomes and roots of P. hexandrum were very effective against Bacillus cereus and Staphylococcus aureus, while podophyllotoxin inhibited the growth of Staphylococcus aureus and Escherichia coli. D. cymosa leaves and roots showed anticholinesterasic and antioxidant activities, respectively. The evaluated extracts showed to be moderately toxic to THP-1 cells. The chromatographic characterization indicated that podophyllotoxin was the major constituent of P. hexandrum extract while kaempferol and its hexoside were the main constituents of D. cymosa leaves and roots, respectively. These results suggest that the podophyllotoxin could be the major antibacterial lignan, while flavonoids could be responsible for the antioxidant activity.