Antiviral effects and possible mechanisms of action of constituents from Brazilian propolis and related compounds

Kwon, Min Jung; Shin, He Min; Perumalsamy, Haribalan; Wang, Xue; Ahn, Young‐Joon

doi:10.1080/00218839.2019.1695715

Cited by 59 publications

(56 citation statements)

References 64 publications

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“…In the same context, our promising candidates like p-coumaric acid, ellagic acid, kaemferol and quercetin were previously found to have potential antiviral activity against the common cold human rhinovirus which is RNA virus like SARS-CoV2. Surprisingly the mentioned bioactive compounds were suggested in the same study to block or reduce the viral entry into the cells to protect the cells from the virus cytopathic effects and subside virus replication (Kwon et al 2019), supporting our virtual screening. Moreover, quercetin and its derivatives were previously confirmed to inhibit the SARS-CoV proteases (Nguyen et al 2012).…”

Section: Resultssupporting

confidence: 81%

In Silico Screening of Potent Bioactive Compounds from Honey Bee Products Against COVID-19 Target Enzymes

Shaldam¹,

Yahya²,

Mohamed³

et al. 2020

Preprint

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From the early days of the COVID-19 pandemic, side by side to immense investigates to design specific drugs or to develop a potential vaccine for the novel coronavirus. Myriads of FDA approved drugs are massively repurposed for COVID-19 treatment based on molecular docking of selected protein targets that play vital for the replication cycle of the virus. Honey bee products are well known of their nutritional values and medicinal effects. Antimicrobial activity of bee products and natural honey have been documented in several clinical studies and was considered a good alternative for antiviral medications to treat some viral infections. Bee products contain bioactive compounds in the form of a collection of phenolic acids, flavonoids and terpenes of natural origin. We revealed by molecular docking the profound binding affinity of 14 selected phenolics and terpenes present in honey and propolis (bees glue) against the main protease (M<sup>pro</sup>) and RNA dependent RNA polymerase (RdRp) enzymes of the novel 2019-nCoV coronavirus. Of these compounds, <i>p</i>-coumaric acid, ellagic acid, kaemferol and quercetin has the strongest interaction with the 2019-nCoV target enzymes, and they may be considered as an effective 2019-nCoV inhibitors.

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Section: Resultssupporting

confidence: 81%

In Silico Screening of Potent Bioactive Compounds from Honey Bee Products Against COVID-19 Target Enzymes

Shaldam¹,

Yahya²,

Mohamed³

et al. 2020

Preprint

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“…Both of these are trusted to boost the immune function, possess a variety of prophylactic and therapeutic activities (Latheef et al, 2017;Munagala et al, 2011). Several studies have provided evidence that honeybee propolis inhibits variety of viruses including herpes simplex virus, sindbis virus, parainfuenze-3 virus, human cytomegalovirus, dengue virus type-2, influenza virus A1 and rhinovirus (Amoros et al, 1994;Kwon et al, 2019;Munagala et al, 2011;Serkedjieva et al, 1992). Withaferin-A (Wi-A), a bioactive withanolide from Ashwagandha, was shown to possess inhibitory activity for HPV and influenza viruses (Cai et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Withanone and Withaferin-A are predicted to interact with transmembrane protease serine 2 (TMPRSS2) and block entry of SARS-CoV-2 into cells

Kumar

Dhanjal

Bhargava

et al. 2020

Journal of Biomolecular Structure and Dynamics

148

143

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Coronavirus disease 2019 (COVID-19) initiated in December 2019 in Wuhan, China and became pandemic causing high fatality and disrupted normal life calling world almost to a halt. Causative agent is a novel coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2/2019-nCoV). While new line of drug/vaccine development has been initiated worldwide , in the current scenario of high infected numbers, severity of the disease and high morbidity, repurposing of the existing drugs is heavily explored. Here, we used a homology-based structural model of transmembrane protease serine 2 (TMPRSS2), a cell surface receptor, required for entry of virus to the target host cell. Using the strengths of molecular docking and molecular dynamics simulations, we examined the binding potential of Withaferin-A (Wi-A), Withanone (Wi-N) and caffeic acid phenethyl ester to TPMRSS2 in comparison to its known inhibitor, Camostat mesylate. We found that both Wi-A and WiN could bind and stably interact at the catalytic site of TMPRSS2. WiN showed stronger interactions with TMPRSS2 catalytic residues than Wi-A and was also able to induce changes in its allosteric site. Furthermore, we investigated the effect of WiN on TMPRSS2 expression in MCF7 cells and found remarkable downregulation of TMPRSS2 mRNA in treated cells predicting dual action of WiN to block SARS-CoV-2 entry into the host cells. Since the natural compounds are easily available/affordable, they may even offer a timely therapeutic/preventive value for the management of SARS-CoV-2 pandemic. We also report that Wi-A/Wi-N content varies in different parts of Ashwagandha and warrants careful attention for their use.

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“…Both of these phytochemicals possess multiple survivorship-boosting capabilities, including reducing N. ceranae spore load, upregulating detoxification genes, and increasing pesticide tolerance [ 25 , 26 , 27 , 29 ]. Furthermore, they both inhibit the replication and production of a large number of viruses, such as Canine Distemper Virus [ 30 ], human rhinovirus [ 31 ], herpes simplex virus [ 63 ], and Japanese encephalitis virus [ 64 ], although these tests have thus far been conducted only in mammalian systems. Our current results do not support the hypothesis that these phytochemicals help combat IAPV infection, but it is difficult to rule out whether or not they activate any of the various defense mechanisms honey bees utilize to defend against viral infection without subsequent molecular analyses.…”

Section: Discussionmentioning

confidence: 99%

“…PCA also upregulates antimicrobial peptide gene expression when fed to larval and adult bees [ 25 , 28 ] and improves honey bee survivorship when infected with Nosema ceranae microsporidian gut parasites [ 29 ]. Both PCA and quercetin have also been shown to possess antiviral qualities; however, these studies have primarily been conducted in human pathogen models (e.g., cell culture systems with model human viruses) [ 30 , 31 ] and not pollinators that normally collect and consume these phytochemicals. For example, PCA inhibited the replication of human rhinovirus [ 31 ], which belongs to the order Picornavirales , to which many of the more frequently encountered bee viruses (DWV, Israeli acute paralysis virus or IAPV, Black queen cell virus or BQCV, and others) also belong [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

“…Both PCA and quercetin have also been shown to possess antiviral qualities; however, these studies have primarily been conducted in human pathogen models (e.g., cell culture systems with model human viruses) [ 30 , 31 ] and not pollinators that normally collect and consume these phytochemicals. For example, PCA inhibited the replication of human rhinovirus [ 31 ], which belongs to the order Picornavirales , to which many of the more frequently encountered bee viruses (DWV, Israeli acute paralysis virus or IAPV, Black queen cell virus or BQCV, and others) also belong [ 32 ]. These commonalities, in conjunction with the anti-DWV effect observed by Palmer-Young et al [ 22 ], suggest that there may be a similar antiviral result when PCA and quercetin are administered to honey bees.…”

Section: Introductionmentioning

confidence: 99%

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Ameliorative Effects of Phytochemical Ingestion on Viral Infection in Honey Bees

Hsieh

Berenbaum

Doležal

2020

Insects

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Honey bee viruses are capable of causing a wide variety of devastating effects, but effective treatments have yet to be discovered. Phytochemicals represent a broad range of substances that honey bees frequently encounter and consume, many of which have been shown to improve honey bee health. However, their effect on bee viruses is largely unknown. Here, we tested the therapeutic effectiveness of carvacrol, thymol, p-coumaric acid, quercetin, and caffeine on viral infection by measuring their ability to improve survivorship in honey bees inoculated with Israeli acute paralysis virus (IAPV) using high-throughput cage bioassays. Among these candidates, caffeine was the only phytochemical capable of significantly improving survivorship, with initial screening showing that naturally occurring concentrations of caffeine (25 ppm) were sufficient to produce an ameliorative effect on IAPV infection. Consequently, we measured the scope of caffeine effectiveness in bees inoculated and uninoculated with IAPV by performing the same type of high-throughput bioassay across a wider range of caffeine concentrations. Our results indicate that caffeine may provide benefits that scale with concentration, though the exact mechanism by which caffeine ingestion improves survivorship remains uncertain. Caffeine therefore has the potential to act as an accessible and inexpensive method of treating viral infections, while also serving as a tool to further understanding of honey bee–virus interactions at a physiological and molecular level.

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Antiviral effects and possible mechanisms of action of constituents from Brazilian propolis and related compounds

Cited by 59 publications

References 64 publications

In Silico Screening of Potent Bioactive Compounds from Honey Bee Products Against COVID-19 Target Enzymes

In Silico Screening of Potent Bioactive Compounds from Honey Bee Products Against COVID-19 Target Enzymes

Withanone and Withaferin-A are predicted to interact with transmembrane protease serine 2 (TMPRSS2) and block entry of SARS-CoV-2 into cells

Ameliorative Effects of Phytochemical Ingestion on Viral Infection in Honey Bees

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