Eleusine indica Inhibits Early and Late Phases of Herpes Simplex Virus Type 1 Replication Cycle and Reduces Progeny Infectivity

Iberahim, Rashidah; Nor, Norefrina Shafinaz Md; Yaacob, Wan Zuhairi Wan; Ibrahim, Nazlina

doi:10.17576/jsm-2018-4707-10

Cited by 3 publications

(4 citation statements)

References 21 publications

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“…Rosmarinic acid content in O. stamineus leaves water extract may also contribute to the antiviral activity against dengue virus type 2 (Wahab et al, 2018). Flavonoids such as naringenin, caffeic acid, p-coumaric acid are found in Eleusine indica and have been previously shown to display virucidal activity (Iberahim et al, 2018). Flavonoids are known to abrogate HHV-1 replication by blocking virus binding to the cell (Bisignano et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Orthosiphon stamineus water extracts inhibit human herpes virus 1 KOS-1 and acyclovir-resistant strains by virucidal activity and suppressing virus early infection

Habboo¹,

Nor²,

Ibrahim³

2020

MJM

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Aim: To determine the efficacy and mode of action of hot and cold water extracts of Orthosiphon stamineus leaves against two strains of human herpes virus 1 (HHV-1) i.e. KOS-1 and acyclovir (ACV)-resistant UKM-1 (UKM-1) strains. Methodology and results: Hot and cold water extracts of O. stamineus were not cytotoxic to vero cells as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) (MTT) assay with 50% cytotoxicity concentration (CC50) values of 3.4 and 3.3 mg/mL respectively. Antiviral activity was determined by plaque reduction assay in post-treatment, pre-treatment and virucidal assays followed by time-addition and time removal assay to relate with the stages during the viral infection cycle. Both extracts displayed antiviral activity against HHV-1 KOS-1 and HHV-1 UKM-1 strains with 50% effective concentration (EC50) values between 0.12-0.15 mg/mL in reducing plaque formation. The calculated selectivity indices (SI) were 23 and 28 for hot and cold water extract respectively, indicating that they have good potential as antiviral agent. The extracts were virucidal towards both HHV-1 KOS-1 and HHV-1 UKM-1 strains which may directly affects the virus structure. This is supported with the fact that exposure of the extracts inhibit viral attachment and penetration to the vero cells. In time-of addition assay, both extracts were effective during the early stage of virus infection cycle for HHV-1 KOS-1 strain which is in parallel with the results from the attachment and penetration studies. For HHV-1 UKM-1 strain, contact to the extracts at any time during post-infection inhibits virus replication and also progeny release. Conclusion, significance and impact of study: Cold and hot water extracts of O. stamineus have good potential as antiviral agent against HHV-1 strain KOS-1 and more importantly against UKM-1 strain which is ACV-resistant. The extracts displayed virucidal effect and inhibition of early virus replication cycle involving viral attachment and penetration to cells.

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Section: Discussionmentioning

confidence: 99%

Orthosiphon stamineus water extracts inhibit human herpes virus 1 KOS-1 and acyclovir-resistant strains by virucidal activity and suppressing virus early infection

Habboo¹,

Nor²,

Ibrahim³

2020

MJM

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“…This assay was conducted according to a published procedure [ 69 ], with minor modifications. Quantitative RT-PCR was performed to determine the effect of the SPD on the transcription of the selected DENV-2 E gene at different replication stages.…”

Section: Methodsmentioning

confidence: 99%

Styrylpyrone Derivative (SPD) Extracted from Goniothalamus umbrosus Binds to Dengue Virus Serotype-2 Envelope Protein and Inhibits Early Stage of Virus Replication

Wahab

Ibrahim

2022

Molecules

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A study was conducted to investigate the anti-viral effect of a styrylpyrone derivative (SPD) called goniothalamin and the effects on the dengue virus serotype 2 (DENV-2) replication cycle. The SPD was prepared from the root of Goniothalamus umbrosus after purification with petroleum ether. The isolated SPD was then subjected to gas chromatography–mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) analyses for structure validation. The cytotoxicity of the SPD was evaluated using a cell viability assay, while the anti-viral activity of the SPD towards DENV-2 was confirmed by conducting a foci reduction assay which involved virus yield reduction, time-of-addition, and time removal assays. Transcriptomic analysis via quantitative real-time polymerase chain reaction (qRT-PCR) using the DENV-2 E gene was conducted to investigate the level of gene transcript. Immunocytochemistry analysis was used to investigate the effects of SPD treatment on protein E expression. Finally, software molecular docking of the SPD and E protein was also performed. The cytotoxicity assay confirmed that the SPD was not toxic to Vero cells, even at the highest concentration tested. In the time-of-addition assay, more than 80% foci reduction was observed when SPDs were administered at 2 h post-infection (hpi), and the reduction percentage then dropped with the delay of the treatment time, suggesting the inhibition of the early replication cycle. However, the time removal assay showed that more than 80% reduction could only be observed after 96 h post-treatment with the SPD. Treatment with the SPD reduced the progeny infectivity when treated for 24 h and was dose-dependent. The result showed that transcript level of the E gene in infected cells treated with the SPD was reduced compared to infected cells without treatment. In immunocytochemistry analysis, the DENV-2 E protein exhibited similar expression trends, shown by the gene transcription level. Molecular docking showed that the SPD can interact with E protein through hydrogen bonds and other interactions. Overall, this study showed that SPDs have the potential to be anti-DENV-2 via a reduction in viral progeny infectivity and a reduction in the expression of the DENV-2 E gene and protein at different phases of viral replication. SPDs should be further researched to be developed into an effective anti-viral treatment, particularly for early-phase dengue viral infection.

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“…The effect of PMFPAE (60 µg/mL) or ACV at 4.5 μg/mL when added at different times beginning from the time of infection was determined according to 23 . Treatments were added to infected cells at time points 2, 4, 6, 8, 10 and 12 hours post-infection (hpi).…”

Section: Time-addition Assaymentioning

confidence: 99%

“…HHV-1 infected cells were treated with PMFPAE at 60 µg/mL or ACV at 4.5 μg/mL and treatment was removed after 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28 and 30 hpi following 23 . Negative control was HHV-1 infected-cells and mock treated with DMEM.…”

Section: Time-removal Assaymentioning

confidence: 99%

Protein from Phaleria macrocarpa Fruit Aqueous Extract Inhibits Early and Late Replication Phases of Human Herpes Virus Type-1

Ismaeel¹,

Dyari²,

Ibrahim³

2022

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Background: Phaleria macrocarpa fruit is known to have protein but the antiviral activity potential has not been explored. Objective: To determine the antiviral activity of Phaleria macrocarpa fruit protein aqueous extract (PMFPAE) and the fractions against human herpesvirus type 1 (HHV-1). Methods: Protein from P. macrocarpa fruit aqueous extract was precipitated using ammonium sulphate and followed by fractionation on Sephadex G-25. Cytotoxicity was determined in Vero cells and followed by determination of antiviral activity by plaque reduction assay against a clinical strain of HHV-1. Effect of PMFPAE on virus replication was determined in pre-treatment, time-addition and time-removal assays. Results: PMFPAE and its fractions were non-cytotoxic to Vero cells with 50% cytotoxic concentration (CC 50 ) values ranged between 96 ± 1.3 to 1450 ± 2 μg/mL. PMFPAE have good anti-HHV-1 activity with Selective Index (SI) of 80.6 but reduces in fractions P 1 to P 6 ranging between 4.2 and 67.9. Fractions with high SI were P 1 and P 2 contained high molecular weight (MW) proteins and P 6 has the lowest MW suggestively peptides. Treatment with PMFPAE to host cells prior to virus infection had little effect on inhibiting HHV-1 replication. Treatment with PMFPAE affects virus early and late replication phase with plaque inhibition percentage increased during 10 th to 16 th hour post-infection. Conclusion: PMFPAE contained non-cytotoxic proteins that affects HHV-1 early and late replication phases. Proteins with high antiviral activity resides in fractions with high MW and very low MW peptides.

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Eleusine indica Inhibits Early and Late Phases of Herpes Simplex Virus Type 1 Replication Cycle and Reduces Progeny Infectivity

Cited by 3 publications

References 21 publications

Orthosiphon stamineus water extracts inhibit human herpes virus 1 KOS-1 and acyclovir-resistant strains by virucidal activity and suppressing virus early infection

Orthosiphon stamineus water extracts inhibit human herpes virus 1 KOS-1 and acyclovir-resistant strains by virucidal activity and suppressing virus early infection

Styrylpyrone Derivative (SPD) Extracted from Goniothalamus umbrosus Binds to Dengue Virus Serotype-2 Envelope Protein and Inhibits Early Stage of Virus Replication

Protein from Phaleria macrocarpa Fruit Aqueous Extract Inhibits Early and Late Replication Phases of Human Herpes Virus Type-1

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