A flavonoid compound library screen revealed potent antiviral activity of plant-derived flavonoids on human enterovirus A71 replication

Min, Nyo; Leong, Pok Thim; Lee, Regina Ching Hua; Khuan, Jeffery Seng Eng; Chu, Justin Jang Hann

doi:10.1016/j.antiviral.2017.12.003

Cited by 35 publications

(24 citation statements)

References 30 publications

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“…It is a methoxyphenyl acetate, a derivative of a flavonoid which was found to possess anti-EV-A71 activity in a recent screening of a flavonoid library. The antiviral activity of pulicarine was associated with inhibition of the 3D polymerase expression in EV-A71 replication process [81].…”

Section: Peracetate Pulicarinementioning

confidence: 96%

“…Quercetagetin, a synthetic derivative of quercetin, was identified to inhibit the RNA replication machinery and viral translation. The flavonoid was found to reduce the activity of the 3D polymerase in vitro [81]. Similarly, chrysosplenetin, a methylated derivative of quercetagetin, was identified to potently inhibit EV-A71 by reducing the production of viral RNA and proteins [80].…”

Section: Quercetin and Its Derivativesmentioning

confidence: 99%

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Flavonoids as Antiviral Agents for Enterovirus A71 (EV-A71)

Lalani

Poh

2020

Viruses

155

101

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Flavonoids are natural biomolecules that are known to be effective antivirals. These biomolecules can act at different stages of viral infection, particularly at the molecular level to inhibit viral growth. Enterovirus A71 (EV-A71), a non-enveloped RNA virus, is one of the causative agents of hand, foot and mouth disease (HFMD), which is prevalent in Asia. Despite much effort, no clinically approved antiviral treatment is available for children suffering from HFMD. Flavonoids from plants serve as a vast reservoir of therapeutically active constituents that have been explored as potential antiviral candidates against RNA and DNA viruses. Here, we reviewed flavonoids as evidence-based natural sources of antivirals against non-picornaviruses and picornaviruses. The detailed molecular mechanisms involved in the inhibition of EV-A71 infections are discussed.

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Section: Peracetate Pulicarinementioning

confidence: 96%

Section: Quercetin and Its Derivativesmentioning

confidence: 99%

Flavonoids as Antiviral Agents for Enterovirus A71 (EV-A71)

Lalani

Poh

2020

Viruses

155

101

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“…Fisetin and quercetagetin fall under the category of flavonols, and are exploited for their antiviral activities (Zakaryan et al 2017). Fisetin was successfully reported to inhibit the replication of dengue virus and enterovirus A71 in vitro (Min et al 2018). The inhibition of hepatitis C virus and the human (2016), Gómez-Calderón et al (2017) cytomegalovirus (HCMV) infection was done by the activity of quercetagetin (Zakaryan et al 2017).…”

Section: Flavonoids As Antiviral Agentsmentioning

confidence: 99%

Phytochemicals as Antiviral Agents: Recent Updates

Ghildiyal

Prakash

Chaudhary

et al. 2020

Plant-Derived Bioactives

124

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“…As antivirals, flavonoids have been shown to execute antiviral activities against many human viruses, including DNA viruses, RNA viruses, and retroviruses, and these have been observed in cell culture and animals (68). Mechanistically, flavonoids function in various pathways of the virus life cycle, including virus entry (69), RNA transcription of the viral genome (70,71), and viral RNA translation (72,73). Flavonoids can inhibit viral protease activity (74,75), viral helicase activity (76,77), and viral (HIV) reverse transcriptase (78,79).…”

Section: B19v Ns1 Endonuclease As a Target For Anti-b19v Drugsmentioning

confidence: 99%

Endonuclease Activity Inhibition of the NS1 Protein of Parvovirus B19 as a Novel Target for Antiviral Drug Development

Peng

Ganaie

Wang

et al. 2019

Antimicrob Agents Chemother

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Human parvovirus B19 (B19V), a member of the genus Erythroparvovirus of the family Parvoviridae, is a small nonenveloped virus that has a single-stranded DNA (ssDNA) genome of 5.6 kb with two inverted terminal repeats (ITRs). B19V infection often results in severe hematological disorders and fetal death in humans. B19V replication follows a model of rolling hairpin-dependent DNA replication, in which the large nonstructural protein NS1 introduces a site-specific single-strand nick in the viral DNA replication origins, which locate at the ITRs. NS1 executes endonuclease activity through the N-terminal origin-binding domain. Nicking of the viral replication origin is a pivotal step in rolling hairpin-dependent viral DNA replication. Here, we developed a fluorophore-based in vitro nicking assay of the replication origin using the origin-binding domain of NS1 and compared it with the radioactive in vitro nicking assay. We used both assays to screen a set of small-molecule compounds (n ϭ 96) that have potential antinuclease activity. We found that the fluorophore-based in vitro nicking assay demonstrates sensitivity and specificity values as high as those of the radioactive assay. Among the 96 compounds, we identified 8 which have an inhibition of Ͼ80% at 10 M in both the fluorophore-based and radioactive in vitro nicking assays. We further tested 3 compounds that have a flavonoid-like structure and an in vitro 50% inhibitory concentration that fell in the range of 1 to 3 M. Importantly, they also exhibited inhibition of B19V DNA replication in UT7/Epo-S1 cells and ex vivo-expanded human erythroid progenitor cells.

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A flavonoid compound library screen revealed potent antiviral activity of plant-derived flavonoids on human enterovirus A71 replication

Cited by 35 publications

References 30 publications

Flavonoids as Antiviral Agents for Enterovirus A71 (EV-A71)

Flavonoids as Antiviral Agents for Enterovirus A71 (EV-A71)

Phytochemicals as Antiviral Agents: Recent Updates

Endonuclease Activity Inhibition of the NS1 Protein of Parvovirus B19 as a Novel Target for Antiviral Drug Development

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