Exploration of natural compounds against the human mpox virus DNA-dependent RNA polymerase in silico

Abduljalil, Jameel M.; Elfiky, Abdo A.; Elgohary, Alaa M.

doi:10.1016/j.jiph.2023.04.019

Cited by 10 publications

(8 citation statements)

References 37 publications

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“…The binding energy ≤-7.0 kcal/mol indicates the stable binding between components and targets. 32 Hence, 21 out of the 34 components may bind tightly with the core targets and play an anti-EV71 role as the average binding energy with the three targets was ≤ −7.0 kcal/mol. As not all the components were available, only nine including rutin, gallic acid, astragalin, rosmarinic acid, caffeic acid, neochlorogenic acid, cryptochlorogenic acid, chlorogenic acid, and hyperoside were selected for pharmacodynamic verification in vitro.…”

Section: Resultsmentioning

confidence: 98%

“…It is generally considered that binding energy less than −7.0 kcal/mol indicates a strong binding activity between the ligand and the receptor. 32 The binding energy between rosmarinic acid and two core targets (AKT1 and ALB) was much lower than −7.0 kcal/mol, indicating it could bind tightly to the target proteins, thereby proving the anti-EV71 activity of rosmarinic acid from the molecular point of view. Besides the anti-EV71 activity, rosmarinic acid was reported to be efficient against a variety of other viruses, including severe acute respiratory syndrome coronavirus, herpes simplex virus, dengue virus, influenza A virus, and hepatitis B virus.…”

Section: Discussionmentioning

confidence: 96%

“…The binding energy ≤-7.0 kcal/ mol indicates the stable binding between components and targets. 32 Hence, 21 out of the 34 components may bind tightly with…”

Section: Network Pharmacologymentioning

confidence: 99%

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Exploration of the in vitro Antiviral Effects and the Active Components of Changyanning Tablets Against Enterovirus 71

Ge,

Zhang,

Cao

et al. 2024

DDDT

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Purpose This study aims to investigate the in vitro antiviral effects of the aqueous solution of Changyanning (CYN) tablets on Enterovirus 71 (EV71), and to analyze its active components. Methods The in vitro anti-EV71 effects of CYN solution and its herbal ingredients were assessed by testing the relative viral RNA (vRNA) expression level and the cell viability rates. Material basis analysis was performed using HPLC-Q-TOF-MS/MS detection. Potential targets and active components were identified by network pharmacology and molecular docking. The screened components were verified by in vitro antiviral experiments. Results CYN solution exerted anti-EV71 activities as the vRNA is markedly reduced after treatment, with a half maximal inhibitory concentration (IC 50 ) of 996.85 μg/mL. Of its five herbal ingredients, aqueous extract of Mosla chinensis (AEMC) and leaves of Liquidambar formosana Hance (AELLF) significantly inhibited the intracellular replication of EV71, and the IC 50 was tested as 202.57 μg/mL and 174.77 μg/mL, respectively. Based on HPLC-Q-TOF-MS/MS results, as well as the comparison with the material basis of CYN solution, a total of 44 components were identified from AEMC and AELLF. Through network pharmacology, AKT1, ALB, and SRC were identified as core targets. Molecular docking performed between core targets and the components indicated that 21 components may have anti-EV71 effects. Of these, nine were selected for in vitro pharmacodynamic verification, and only rosmarinic acid manifested in vitro anti-EV71 activity, with an IC 50 of 11.90 μg/mL. Moreover, rosmarinic acid can stably bind with three core targets by forming hydrogen bonds. Conclusion CYN solution has inhibitory effects on EV71 replication in vitro, and its active component was identified as rosmarinic acid. Our study provides a new approach for screening and confirmation of the effective components in Chinese herbal preparation.

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Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 96%

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Exploration of the in vitro Antiviral Effects and the Active Components of Changyanning Tablets Against Enterovirus 71

Ge,

Zhang,

Cao

et al. 2024

DDDT

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“…Recent studies indicated that vRNAP has emerged as a promising drug target for developing effective antiviral drugs against DNA viruses ( Abduljalil and Elfiky, 2022 ). For example, two natural compounds (Comp289 (CNP0158693) NA and Comp441 (CNP0267280) Salpichrolide J) have been recently reported to be the drug target against the DNA-dependent RNA polymerase of human Mpox virus in silico ( Abduljalil et al, 2023 ). Using molecular modeling approach, betulinic acid (BA), a pentacyclic triterpene, has also been found to be a potential inhibitor against DNA-dependent RNA polymerase ( Dutt et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Genistein is effective in inhibiting Orf virus infection in vitro by targeting viral RNA polymerase subunit RPO30 protein

Lv,

Fang,

Guan

et al. 2024

Front. Microbiol.

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Orf virus (ORFV), a typical member of the genus Parapoxvirus, Poxvirus family, causes a contagious pustular dermatitis in sheep, goats, and humans. Poxviruses encode a multisubunit DNA-dependent RNA polymerase (vRNAP) that carries out viral gene expression in the host cytoplasm, which is a viral factor essential to poxvirus replication. Due to its vital role in viral life, vRNAP has emerged as one of the potential drug targets. In the present study, we investigated the antiviral effect of genistein against ORFV infection. We provided evidence that genistein exerted antiviral effect through blocking viral genome DNA transcription/replication and viral protein synthesis and reducing viral progeny, which were dosedependently decreased in genistein-treated cells. Furthermore, we identified that genistein interacted with the vRNAP RPO30 protein by CETSA, molecular modeling and Fluorescence quenching, a novel antiviral target for ORFV. By blocking vRNAP RPO30 protein using antibody against RPO30, we confirmed that the inhibitory effect exerted by genistein against ORFV infection is mediated through the interaction with RPO30. In conclusion, we demonstrate that genistein effectively inhibits ORFV transcription in host cells by targeting vRNAP RPO30, which might be a promising drug candidate against poxvirus infection.

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“…Several small molecule compounds with inhibitory activity against DdRp have been discovered through computer-assisted drug design. 121 – 123 However, further researches are needed to validate these identified candidate compounds, evaluate their safety and effectiveness, and ultimately progress them to the clinical application stage. The endoplasmic reticulum (ER) plays a crucial role in enveloping and stabilizing the viral genome.…”

Section: The Life Cycle Of Mpox Virus and The Discovery Of Anti-mpox ...mentioning

confidence: 99%

Mpox (formerly monkeypox): pathogenesis, prevention and treatment

Lu,

Xing,

Wang

et al. 2023

Sig Transduct Target Ther

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In 2022, a global outbreak of Mpox (formerly monkeypox) occurred in various countries across Europe and America and rapidly spread to more than 100 countries and regions. The World Health Organization declared the outbreak to be a public health emergency of international concern due to the rapid spread of the Mpox virus. Consequently, nations intensified their efforts to explore treatment strategies aimed at combating the infection and its dissemination. Nevertheless, the available therapeutic options for Mpox virus infection remain limited. So far, only a few numbers of antiviral compounds have been approved by regulatory authorities. Given the high mutability of the Mpox virus, certain mutant strains have shown resistance to existing pharmaceutical interventions. This highlights the urgent need to develop novel antiviral drugs that can combat both drug resistance and the potential threat of bioterrorism. Currently, there is a lack of comprehensive literature on the pathophysiology and treatment of Mpox. To address this issue, we conducted a review covering the physiological and pathological processes of Mpox infection, summarizing the latest progress of anti-Mpox drugs. Our analysis encompasses approved drugs currently employed in clinical settings, as well as newly identified small-molecule compounds and antibody drugs displaying potential antiviral efficacy against Mpox. Furthermore, we have gained valuable insights from the process of Mpox drug development, including strategies for repurposing drugs, the discovery of drug targets driven by artificial intelligence, and preclinical drug development. The purpose of this review is to provide readers with a comprehensive overview of the current knowledge on Mpox.

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Exploration of natural compounds against the human mpox virus DNA-dependent RNA polymerase in silico

Cited by 10 publications

References 37 publications

Exploration of the in vitro Antiviral Effects and the Active Components of Changyanning Tablets Against Enterovirus 71

Exploration of the in vitro Antiviral Effects and the Active Components of Changyanning Tablets Against Enterovirus 71

Genistein is effective in inhibiting Orf virus infection in vitro by targeting viral RNA polymerase subunit RPO30 protein

Mpox (formerly monkeypox): pathogenesis, prevention and treatment

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