Natural Products Isolated from Oriental Medicinal Herbs Inactivate Zika Virus

Batista, Mariana Nogueira; Braga, Ana Cláudia Silva; Campos, Guilherme Rodrigues Fernandes; Souza, Marcos Michel de; Matos, Renata Prandini Adum de; Lopes, Tairine Zara; Cândido, Natália Maria; Lima, Maria Letícia Duarte; Machado, Francielly Cristina; Andrade, Stephane Tereza Queiroz de; Bittar, Cíntia; Nogueira, Maurício Lacerda; Carneiro, Bruno Moreira; Mariutti, Ricardo Barros; Arni, Raghuvir K.; Calmon, Marília Freitas; Rahal, Paula

doi:10.3390/v11010049

Cited by 54 publications

(44 citation statements)

References 56 publications

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“…Moreover, some compounds, such as lycorine, emodin, and procyanidin, have been proven to be effective in inhibiting flavivirus or HCV infections via different mechanisms (16)(17)(18)(19)(20). Our high-content screening assay design could identify compounds that inhibit JEV viral entry, translation, and RNA synthesis.…”

Section: Ouabain Blocks Jev Infectionmentioning

confidence: 99%

Screening of Natural Extracts for Inhibitors against Japanese Encephalitis Virus Infection

Guo

Jia

Liu

et al. 2020

Antimicrob Agents Chemother

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The mosquito-borne Japanese encephalitis virus (JEV) causes serious illness worldwide that is associated with high morbidity and mortality. Currently, there are no effective drugs approved for the treatment of JEV infection. Drug-repurposing screening is an alternative approach to discover potential antiviral agents. In this study, high-content screening (HCS) of a natural extracts library was performed, and two hit FDA-approved Na ϩ /K ϩ -ATPase inhibitors, ouabain and digoxin, were identified as having robust efficiency against JEV infection with the selectivity indexes over 1,000. The results indicated that ouabain and digoxin blocked the JEV infection at the replication stage by targeting the Na ϩ /K ϩ -ATPase. Furthermore, it was proven that ouabain significantly reduced the morbidity and mortality caused by JEV in a BALB/c mouse model. This work demonstrated that Na ϩ /K ϩ -ATPase could serve as the target of treatment of JEV infection, and ouabain has the potential to be developed as an effective anti-JEV drug.Ethics statements and mice. All animal experimental procedures were carried out according to ethical guidelines and were approved by the Animal Care Committee of the Wuhan Institute of Virology (permit number, WIVA25201705).Cells and viruses. BHK-21, Vero, and Huh-7 cells were maintained in Dulbecco modified Eagle medium (DMEM) (HyClone, Logan, UT, USA) supplement with 10% fetal bovine serum (FBS) (Gibco, Grand Island, NY, USA). U251 cells were maintained in minimum essential medium (MEM) (HyClone) supplement with 10% FBS. JEV AT31 and SA14 strains were generated by using the infectious clones of pMWJEAT-AT31 (kindly provided by T. Wakita, Tokyo Metropolitan Institute for Neuroscience) and pACYC-JEV-SA14 (GenBank accession no. U14163) as previously described (32), respectively. The infectious clone plasmids were linearized, subjected to in vitro transcription, and electroporated into BHK-21 cells. Three days later, the supernatant was collected and stored at Ϫ80°C in aliquots (33, 34). The virus stocks were propagated and titrated by a plaque assay in BHK-21 cells.Optimization of HCS assay conditions. The cell density, infective dose, and assay endpoint were optimized for the HCS assay. Different densities (2,000 to 10,000 cells per well) of Vero cells were infected at MOI values ranging from 0.2 to 1. Cell viability was detected at different times (24 to 72 h) after JEV inoculation. The appropriate cell density, infective dose, and assay endpoint for the HCS assay were selected by comparing the signal-to-basal ratio (S/B), the coefficient of variation (CV), and z values under different conditions as previously described (11); 10 M manidipine and 0.5% DMSO were used as positive and negative controls, respectively.HCS assay of drug library screening. A library of 1,034 compounds from natural extracts was purchased from Weikeqi Biotech (Sichuan, China). Compounds were stored as 10 mM stock solutions in DMSO at -80°C until use. As shown in Fig. 1A, Vero cells were dissociated and seeded at a density of ...

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Section: Ouabain Blocks Jev Infectionmentioning

confidence: 99%

Screening of Natural Extracts for Inhibitors against Japanese Encephalitis Virus Infection

Guo

Jia

Liu

et al. 2020

Antimicrob Agents Chemother

View full text Add to dashboard Cite

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“…In February 2016, the World Health Organization (WHO) declared ZIKV to be a Public Health Emergency of International Concern (PHEIC) [13]. Strategies of fighting ZIKV infection include the development of vaccines and the screening of antiviral agents that inhibit different stages of the viral life cycle [14]. Unfortunately, no approved antiviral ZIKV agents are currently available.…”

Section: Introductionmentioning

confidence: 99%

Cephalotaxine inhibits Zika infection by impeding viral replication and stability

Lai

2020

Biochemical and Biophysical Research Communications

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a b s t r a c tThe Zika virus (ZIKV) is a mosquito-borne flavivirus that has reemerged as a serious public health problem around the world. Syndromes of infected people range from asymptomatic infections to severe neurological disorders, such as Guillain-Barr e syndrome and microcephaly. Screening anti-ZIKV drugs derived from Chinese medicinal herbs is one method of identifying antiviral agents. In this paper, we report that (1) Cephalotaxine (CET), an alkaloid isolated from Cephalotaxus drupacea, was effective in inhibiting ZIKV activity in vitro (i.e., in Vero and A549 cell lines) and (2) the mechanisms which underlie these effects involve virucidal activity and a decrease in viral replication. Specifically, CET was found to decrease ZIKV RNA and viral protein expression, inhibit ZIKV replication, and inhibit ZIKV mRNA/protein production. We also determined that CET is effective in inhibiting dengue virus 1e4 (DENV1-4). Taken together, our findings indicate that CET could be an effective lead compound in the treatment of ZIKV and also suggest that further investigation and development of CET-derived drugs may lead to a new class of anti-Flavivirus medications.

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“…The development of plant-derived substances used as nutraceuticals and capable of inhibiting the infection of emerging viruses represents an attractive and eco-friendly strategy [ 41 ]. Indeed, several studies have shown that plants represent a promising source of antivirals against emerging viruses [ 17 , 18 , 19 , 22 , 23 , 24 , 30 , 42 , 43 ]. In this study, we showed for the first time that papaya fruit pulp inhibited the infection of A549 cells by the epidemic ZIKV without reducing cell viability.…”

Section: Resultsmentioning

confidence: 99%

“…Neither an effective treatment nor a vaccine is available for ZIKV. Given that several countries around the world are at risk of ZIKV outbreaks, it is still of high importance to develop antiviral strategies that include the use of nutraceuticals that can be used to prevent ZIKV infection [17][18][19][20][21]. Several polyphenol-rich extracts from Reunion Island have been reported to prevent ZIKV infection in vitro [22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Papaya Fruit Pulp and Resulting Lactic Fermented Pulp Exert Antiviral Activity against Zika Virus

et al. 2020

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There are a several emerging and re-emerging RNA viruses that are prevalent around the world for which there are no licensed vaccines or antiviral drugs. Zika virus (ZIKV) is an example of an emerging virus that has become a significant concern worldwide because of its association with severe congenital malformations and neurological disorders in adults. Several polyphenol-rich extracts from plants were used as nutraceuticals which exhibit potent in vitro antiviral effects. Here, we demonstrated that the papaya pulp extracted from Carica papaya fruit inhibits the infection of ZIKV in human cells without loss of cell viability. At the non-cytotoxic concentrations, papaya pulp extract has the ability to reduce the virus progeny production in ZIKV-infected human cells by at least 4-log, regardless of viral strains tested. Time-of-drug-addition assays revealed that papaya pulp extract interfered with the attachment of viral particles to the host cells. With a view of preserving the properties of papaya pulp over time, lactic fermentation based on the use of bacterial strains Weissella cibaria 64, Lactobacillus plantarum 75 and Leuconostoc pseudomesenteroides 56 was performed and the resulting fermented papaya pulp samples were tested on ZIKV. We found that lactic fermentation of papaya pulp causes a moderate loss of antiviral activity against ZIKV in a bacterial strain-dependent manner. Whereas IC50 of the papaya pulp extract was 0.3 mg/mL, we found that fermentation resulted in IC50 up to 4 mg/mL. We can conclude that papaya pulp possesses antiviral activity against ZIKV and the fermentation process has a moderate effect on the antiviral effect.

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Natural Products Isolated from Oriental Medicinal Herbs Inactivate Zika Virus

Cited by 54 publications

References 56 publications

Screening of Natural Extracts for Inhibitors against Japanese Encephalitis Virus Infection

Screening of Natural Extracts for Inhibitors against Japanese Encephalitis Virus Infection

Cephalotaxine inhibits Zika infection by impeding viral replication and stability

Papaya Fruit Pulp and Resulting Lactic Fermented Pulp Exert Antiviral Activity against Zika Virus

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