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27 pages, 3210 KiB

Open AccessArticle

Development of Provesicular Nanodelivery System of Curcumin as a Safe and Effective Antiviral Agent: Statistical Optimization, In Vitro Characterization, and Antiviral Effectiveness

by Farid A. Badria, Abdelaziz E. Abdelaziz, Amira H. Hassan, Abdullah A. Elgazar and Eman A. Mazyed

Molecules 2020, 25(23), 5668; https://doi.org/10.3390/molecules25235668 - 01 Dec 2020

Cited by 30 | Viewed by 2960

Abstract

Curcumin is a natural compound that has many medical applications. However, its low solubility and poor stability could impede its clinical applications. The present study aimed to formulate dry proniosomes to overcome these pitfalls and improve the therapeutic efficacy of Curcumin. Curcumin-loaded proniosomes [...] Read more.

Curcumin is a natural compound that has many medical applications. However, its low solubility and poor stability could impede its clinical applications. The present study aimed to formulate dry proniosomes to overcome these pitfalls and improve the therapeutic efficacy of Curcumin. Curcumin-loaded proniosomes were fabricated by the slurry method according to 3² factorial design using Design-Expert software to demonstrate the impact of different independent variables on entrapment efficiency (EE%) and % drug released after 12 h (Q_12h). The optimized formula (F5) was selected according to the desirability criteria. F5 exhibited good flowability and appeared, after reconstitution, as spherical nanovesicles with EE% of 89.94 ± 2.31% and Q_12h of 70.89 ± 1.62%. F5 demonstrated higher stability and a significant enhancement of Q_12h than the corresponding niosomes. The docking study investigated the ability of Curcumin to bind effectively with the active site of DNA polymerase of Herpes simplex virus (HSV). The antiviral activity and the safety of F5 were significantly higher than Curcumin. F5 improved the safety of Acyclovir (ACV) and reduced its effective dose that produced a 100% reduction of viral plaques. Proniosomes could be promising stable carriers of Curcumin to be used as a safe and efficient antiviral agent. Full article

(This article belongs to the Special Issue Herbal Medicines as Antivirals)

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16 pages, 2068 KiB

Open AccessArticle

Dibromopinocembrin and Dibromopinostrobin Are Potential Anti-Dengue Leads with Mild Animal Toxicity

by Siwaporn Boonyasuppayakorn, Thanaphon Saelee, Peerapat Visitchanakun, Asada Leelahavanichkul, Kowit Hengphasatporn, Yasuteru Shigeta, Thao Nguyen Thanh Huynh, Justin Jang Hann Chu, Thanyada Rungrotmongkol and Warinthorn Chavasiri

Molecules 2020, 25(18), 4154; https://doi.org/10.3390/molecules25184154 - 11 Sep 2020

Cited by 16 | Viewed by 3167

Abstract

Dengue infection is one of the most deleterious public health concerns for two-billion world population being at risk. Plasma leakage, hemorrhage, and shock in severe cases were caused by immunological derangement from secondary heterotypic infection. Flavanone, commonly found in medicinal plants, previously showed [...] Read more.

Dengue infection is one of the most deleterious public health concerns for two-billion world population being at risk. Plasma leakage, hemorrhage, and shock in severe cases were caused by immunological derangement from secondary heterotypic infection. Flavanone, commonly found in medicinal plants, previously showed potential as anti-dengue inhibitors for its direct antiviral effects and suppressing the pro-inflammatory cytokine from dengue immunopathogenesis. Here, we chemically modified flavanones, pinocembrin and pinostrobin, by halogenation and characterized them as potential dengue 2 inhibitors and performed toxicity tests in human-derived cells and in vivo animal model. Dibromopinocembrin and dibromopinostrobin inhibited dengue serotype 2 at the EC₅₀s of 2.0640 ± 0.7537 and 5.8567 ± 0.5074 µM with at the CC₅₀s of 67.2082 ± 0.9731 and >100 µM, respectively. Both of the compounds also showed minimal toxicity against adult C57BL/6 mice assessed by ALT and Cr levels in day one, three, and eight post-intravenous administration. Computational studies suggested the potential target be likely the NS5 methyltransferase at SAM-binding pocket. Taken together, these two brominated flavanones are potential leads for further drug discovery investigation. Full article

(This article belongs to the Special Issue Herbal Medicines as Antivirals)

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14 pages, 2536 KiB

Open AccessArticle

Harringtonine Inhibits Zika Virus Infection through Multiple Mechanisms

by Zheng-Zong Lai, Yi-Jung Ho and Jeng-Wei Lu

Molecules 2020, 25(18), 4082; https://doi.org/10.3390/molecules25184082 - 07 Sep 2020

Cited by 12 | Viewed by 2961

Abstract

Mosquito-borne Zika virus (ZIKV) is a Flavivirus that came under intense study from 2014 to 2016 for its well-known ability to cause congenital microcephaly in fetuses and neurological Guillain–Barré disease in adults. Substantial research on screening antiviral agents against ZIKV and preventing ZIKV [...] Read more.

Mosquito-borne Zika virus (ZIKV) is a Flavivirus that came under intense study from 2014 to 2016 for its well-known ability to cause congenital microcephaly in fetuses and neurological Guillain–Barré disease in adults. Substantial research on screening antiviral agents against ZIKV and preventing ZIKV infection are globally underway, but Food and Drug Administration (FDA)-approved treatments are not available yet. Compounds from Chinese medicinal herbs may offer an opportunity for potential therapies for anti-ZIKV infection. In this study, we evaluated the antiviral efficacy of harringtonine against ZIKV. Harringtonine possessed anti-ZIKV properties against the binding, entry, replication, and release stage through the virus life cycle. In addition, harringtonine have strong virucidal effects in ZIKV and exhibited prophylaxis antiviral ability prior ZIKV infection. The antiviral activity also observed in the treatment against Japanese encephalitis reporter virus (RP9-GFP strain). Overall, this study demonstrated that harringtonine would be a favorable potential candidate for the development of anti-ZIKV infection therapies. Full article

(This article belongs to the Special Issue Herbal Medicines as Antivirals)

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14 pages, 2191 KiB

Open AccessArticle

Putative SARS-CoV-2 M^pro Inhibitors from an In-House Library of Natural and Nature-Inspired Products: A Virtual Screening and Molecular Docking Study

by Stefania Mazzini, Loana Musso, Sabrina Dallavalle and Roberto Artali

Molecules 2020, 25(16), 3745; https://doi.org/10.3390/molecules25163745 - 17 Aug 2020

Cited by 30 | Viewed by 4621

Abstract

A novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) has been the cause of a recent global pandemic. The highly contagious nature of this life-threatening virus makes it imperative to find therapies to counteract its diffusion. The main protease (M^pro) [...] Read more.

A novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) has been the cause of a recent global pandemic. The highly contagious nature of this life-threatening virus makes it imperative to find therapies to counteract its diffusion. The main protease (M^pro) of SARS-CoV-2 is a promising drug target due to its indispensable role in viral replication inside the host. Using a combined two-steps approach of virtual screening and molecular docking techniques, we have screened an in-house collection of small molecules, mainly composed of natural and nature-inspired compounds. The molecules were selected with high structural diversity to cover a wide range of chemical space into the enzyme pockets. Virtual screening experiments were performed using the blind docking mode of the AutoDock Vina software. Virtual screening allowed the selection of structurally heterogeneous compounds capable of interacting effectively with the enzymatic site of SARS-CoV-2 M^pro. The compounds showing the best interaction with the protein were re-scored by molecular docking as implemented in AutoDock, while the stability of the complexes was tested by molecular dynamics. The most promising candidates revealed a good ability to fit into the protein binding pocket and to reach the catalytic dyad. There is a high probability that at least one of the selected scaffolds could be promising for further research Full article

(This article belongs to the Special Issue Herbal Medicines as Antivirals)

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17 pages, 2318 KiB

Open AccessArticle

The Geraniin-Rich Extract from Reunion Island Endemic Medicinal Plant Phyllanthus phillyreifolius Inhibits Zika and Dengue Virus Infection at Non-Toxic Effect Doses in Zebrafish

by Juliano G. Haddad, Dovilė Grauzdytė, Andrea Cristine Koishi, Wildriss Viranaicken, Petras Rimantas Venskutonis, Claudia Nunes Duarte dos Santos, Philippe Desprès, Nicolas Diotel and Chaker El Kalamouni

Molecules 2020, 25(10), 2316; https://doi.org/10.3390/molecules25102316 - 15 May 2020

Cited by 19 | Viewed by 3713

Abstract

The mosquito-borne viruses dengue (DENV) and Zika (ZIKV) viruses are two medically important pathogens in tropical and subtropical regions of the world. There is an urgent need of therapeutics against DENV and ZIKV, and medicinal plants are considered as a promising source of [...] Read more.

The mosquito-borne viruses dengue (DENV) and Zika (ZIKV) viruses are two medically important pathogens in tropical and subtropical regions of the world. There is an urgent need of therapeutics against DENV and ZIKV, and medicinal plants are considered as a promising source of antiviral bioactive metabolites. In the present study, we evaluated the ability of Phyllanthus phillyreifolius, an endemic medicinal plant from Reunion Island, to prevent DENV and ZIKV infection in human cells. At non-cytotoxic concentration in vitro, incubation of infected A549 cells with a P. phillyreifolius extract or its major active phytochemical geraniin resulted in a dramatic reduction of virus progeny production for ZIKV as well as four serotypes of DENV. Virological assays showed that P. phillyreifolius extract-mediated virus inhibition relates to a blockade in internalization of virus particles into the host cell. Infectivity studies on ZIKV showed that both P. phillyreifolius and geraniin cause a loss of infectivity of the viral particles. Using a zebrafish model, we demonstrated that administration of P. phillyreifolius and geraniin has no effect on zebrafish locomotor activity while no morbidity nor mortality was observed up to 5 days post-inoculation. Thus, P. phillyreifolius could act as an important source of plant metabolite geraniin which is a promising antiviral compound in the fight against DENV and ZIKV. Full article

(This article belongs to the Special Issue Herbal Medicines as Antivirals)

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18 pages, 8473 KiB

Open AccessArticle

Discordant Activity of Kaempferol Towards Dengue Virus and Japanese Encephalitis Virus

by Chit Care, Wannapa Sornjai, Janejira Jaratsittisin, Atitaya Hitakarun, Nitwara Wikan, Kanokporn Triwitayakorn and Duncan R. Smith

Molecules 2020, 25(5), 1246; https://doi.org/10.3390/molecules25051246 - 10 Mar 2020

Cited by 25 | Viewed by 3681

Abstract

Kaempferol, a plant-derived flavonoid, has been reported to have activity against Japanese encephalitis virus (JEV) in BHK-21 cells. To determine the broader utility of this compound, we initially evaluated the activity of kaempferol against JEV and dengue virus (DENV) in HEK293T/17 cells. Results [...] Read more.

Kaempferol, a plant-derived flavonoid, has been reported to have activity against Japanese encephalitis virus (JEV) in BHK-21 cells. To determine the broader utility of this compound, we initially evaluated the activity of kaempferol against JEV and dengue virus (DENV) in HEK293T/17 cells. Results showed no significant antiviral activity against either virus. We subsequently investigated the activity of kaempferol against both JEV and DENV in BHK-21 cells. Results showed a significant inhibition of JEV infection but, surprisingly, a significant enhancement of DENV infection. The effect of kaempferol on both host protein expression and transcription was investigated and both transcriptional and translational inhibitory effects were observed, although a more marked effect was observed on host cell protein expression. Markedly, while GRP78 was increased in DENV infected cells treated with kaempferol, it was not increased in JEV infected cells treated with kaempferol. These results show that cellular alteration induced by one compound can have opposite effects on viruses from the same family, suggesting the presence of distinct replication strategies for these two viruses. Full article

(This article belongs to the Special Issue Herbal Medicines as Antivirals)

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Review

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30 pages, 36558 KiB

Open AccessReview

Antiviral Activity of Jamaican Medicinal Plants and Isolated Bioactive Compounds

by Henry Lowe, Blair Steele, Joseph Bryant, Emadelden Fouad, Ngeh Toyang and Wilfred Ngwa

Molecules 2021, 26(3), 607; https://doi.org/10.3390/molecules26030607 - 25 Jan 2021

Cited by 20 | Viewed by 13741

Abstract

Plants have had historical significance in medicine since the beginning of civilization. The oldest medical pharmacopeias of the African, Arabian, and Asian countries solely utilize plants and herbs to treat pain, oral diseases, skin diseases, microbial infections, multiple types of cancers, reproductive disorders [...] Read more.

Plants have had historical significance in medicine since the beginning of civilization. The oldest medical pharmacopeias of the African, Arabian, and Asian countries solely utilize plants and herbs to treat pain, oral diseases, skin diseases, microbial infections, multiple types of cancers, reproductive disorders among a myriad of other ailments. The World Health Organization (WHO) estimates that over 65% of the world population solely utilize botanical preparations as medicine. Due to the abundance of plants, plant-derived medicines are more readily accessible, affordable, convenient, and have safer side-effect profiles than synthetic drugs. Plant-based decoctions have been a significant part of Jamaican traditional folklore medicine. Jamaica is of particular interest because it has approximately 52% of the established medicinal plants that exist on earth. This makes the island particularly welcoming for rigorous scientific research on the medicinal value of plants and the development of phytomedicine thereof. Viral infections caused by the human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2), hepatitis virus B and C, influenza A virus, and the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) present a significant global burden. This is a review of some important Jamaican medicinal plants, with particular reference to their antiviral activity. Full article

(This article belongs to the Special Issue Herbal Medicines as Antivirals)

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21 pages, 11653 KiB

Open AccessFeature PaperReview

Antiviral Natural Products for Arbovirus Infections

by Vanessa Shi Li Goh, Chee-Keng Mok and Justin Jang Hann Chu

Molecules 2020, 25(12), 2796; https://doi.org/10.3390/molecules25122796 - 17 Jun 2020

Cited by 35 | Viewed by 5100

Abstract

Over the course of the last 50 years, the emergence of several arboviruses have resulted in countless outbreaks globally. With a high proportion of infections occurring in tropical and subtropical regions where arthropods tend to be abundant, Asia in particular is a region [...] Read more.

Over the course of the last 50 years, the emergence of several arboviruses have resulted in countless outbreaks globally. With a high proportion of infections occurring in tropical and subtropical regions where arthropods tend to be abundant, Asia in particular is a region that is heavily affected by arboviral diseases caused by dengue, Japanese encephalitis, West Nile, Zika, and chikungunya viruses. Major gaps in protection against the most significant emerging arboviruses remains as there are currently no antivirals available, and vaccines are only available for some. A potential source of antiviral compounds could be discovered in natural products—such as vegetables, fruits, flowers, herbal plants, marine organisms and microorganisms—from which various compounds have been documented to exhibit antiviral activities and are expected to have good tolerability and minimal side effects. Polyphenols and plant extracts have been extensively studied for their antiviral properties against arboviruses and have demonstrated promising results. With an abundance of natural products to screen for new antiviral compounds, it is highly optimistic that natural products will continue to play an important role in contributing to antiviral drug development and in reducing the global infection burden of arboviruses. Full article

(This article belongs to the Special Issue Herbal Medicines as Antivirals)

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