Curcumin (Yellow Mustard) and Brilacidin as a Broad-Spectrum Inhibitor of Enveloped, Acutely Infectious Viruses, Fungal, and Bacterial Infections
by
Carol A. Anderson, Michael D. Barrera, Niloufar A. Boghdeh, Miata Smith, Farhang Alem, and
Aarthi Narayanan
Center for Infectious Disease Research, School of Systems Biology, George Mason University, Manassas, VA 20110, USA Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Microorganisms 2024, 12(1), 54; https://doi.org/10.3390/microorganisms12010054
Submission received: 24 October 2023 / Revised: 7 December 2023 / Accepted: 26 December 2023 / Published: 28 December 2023
(This article belongs to the Special Issue Emerging Viruses and Antiviral Drugs, 2nd Edition)
Abstract
Alphaviruses, belonging to the Togaviridae family, and bunyaviruses, belonging to the Paramyxoviridae family, are a global health problem and lack FDA-approved vaccines and therapeutics.
The alphaviruses Venezuelan equine encephalitis virus (VEEV) and eastern equine encephalitis virus (EEEV) are known to cause severe encephalitis, whereas Sindbis virus (SINV) causes arthralgia potentially persisting for years after initial infection. The bunyavirus Rift Valley Fever virus (RVFV) can lead to blindness, liver failure, and hemorrhagic fever. Brilacidin, a small molecule that was designed de novo based on naturally occurring host defensins, was investigated for its antiviral activity against these viruses in human small airway epithelial cells (HSAECs) and African green monkey kidney cells (Veros). This testing was further expanded into a non-enveloped Echovirus, a Picornavirus, to further demonstrate brilacidin’s effect on early steps of the viral infectious cycle that leads to inhibition of viral load. Brilacidin demonstrated antiviral activity against alphaviruses VEEV TC-83, VEEV TrD, SINV, EEEV, and bunyavirus RVFV.
The inhibitory potential of brilacidin against the viruses tested in this study was dependent on the dosing strategy which necessitated compound addition pre- and post-infection, with addition only at the post-infection stage not eliciting a robust inhibitory response. The inhibitory activity of brilacidin was only modest in the context of the non-enveloped Picornavirus Echovirus, suggesting brilacidin may be less potent against non-enveloped viruses.
However Brilacidin key feature is to destroy bacterial membranes and enveloped viruses protective outer layer. It also destroys protein spikes. This makes viruses and bacteria extremely vulnerable to common therapeutics such as curcumin.
“Something a simple as yellow mustard combined with Brilacidin will induce self inoculation in the human immune system.”
Curcumin is a powerful Antiviral, Anti Bacterial, Anti Fungal Agent
Morgan R Jennings 1,2, Robin J Parks 1,2,3,4,*
•
• PMCID: PMC7693600PMID: 33142686
Abstract
Curcumin, the primary curcuminoid compound found in turmeric spice, has shown broad activity as an antimicrobial agent, limiting the replication of many different fungi, bacteria and viruses. In this review, we summarize recent studies supporting the development of curcumin and its derivatives as broad-spectrum antiviral agents.
Keywords: curcumin, antiviral, broad-spectrum, phytochemical
1. Introduction
Curcumin (diferuloylmethane) is the primary curcuminoid derived from the rhizome of Curcuma longa plant [1,2], and is typically used both as a strong food dye and consumed as a spice in the form of turmeric [1]. In addition, curcumin has seen wide use in traditional medicine throughout Asia, due to its anti-inflammatory and wound-healing properties [3,4]. Modern research has also demonstrated that curcumin has diverse biological functions, with reported anti-cancer, antioxidant and anti-microbial properties [3,5,6]. Curcumin can act not only as an anti-fungal and anti-bacterial compound, but also as an anti-viral compound, inhibiting replication in a wide-range of viruses [7], as summarized in Table 1. In this review, recent research into the antiviral properties of curcumin, its derivatives, and formulations will be discussed.
Table 1.
Pathways/processes impacted by curcumin and analogues, and their effect on viruses.
Pathway/Process and Antiviral Activity.
Viral entry - Dengue virus, Viral hemorrhagic septicemia virus
Replication - Dengue virus
Anti-inflammation Replication- Human immunodeficiency virus
Antioxidation Replication - Human immunodeficiency virus (HIV)
APE1 redox reactions Replication- Kaposi’s sarcoma-associated herpesvirus
Cell lipogenesis Replication - Dengue virus
Cleavage of eIF4G Protein expression- Enterovirus 71
Conformation of viral/cellular surface proteins Viral attachment - Zika virus, Chikungunya virus, Vesicular stomatitis virus, Human respiratory syncytial virus
HSC71 expression,Viral entry, - Viral hemorrhagic septicemia virus
NF-κB signalling Replication - Influenza A virus
Viral egress- Herpes simplex virus 2
PKCδ phosphorylation Protein expression - Enterovirus 71
ROS production Viricidal - Norovirus
Lipid raft formation - Bovine herpes virus 1
Viral enzymes Viral egress Viral protease - Influenza A virus Dengue virus
Viral proteins Viral entry - Influenza A virus
Porcine reproductive and respiratory syndrome virus
Viral protein degradation - HIV
Viricidal - Norovirus
by
Carol A. Anderson, Michael D. Barrera, Niloufar A. Boghdeh, Miata Smith, Farhang Alem, and
Aarthi Narayanan
Center for Infectious Disease Research, School of Systems Biology, George Mason University, Manassas, VA 20110, USA Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Microorganisms 2024, 12(1), 54; https://doi.org/10.3390/microorganisms12010054
Submission received: 24 October 2023 / Revised: 7 December 2023 / Accepted: 26 December 2023 / Published: 28 December 2023
(This article belongs to the Special Issue Emerging Viruses and Antiviral Drugs, 2nd Edition)
Abstract
Alphaviruses, belonging to the Togaviridae family, and bunyaviruses, belonging to the Paramyxoviridae family, are a global health problem and lack FDA-approved vaccines and therapeutics.
The alphaviruses Venezuelan equine encephalitis virus (VEEV) and eastern equine encephalitis virus (EEEV) are known to cause severe encephalitis, whereas Sindbis virus (SINV) causes arthralgia potentially persisting for years after initial infection. The bunyavirus Rift Valley Fever virus (RVFV) can lead to blindness, liver failure, and hemorrhagic fever. Brilacidin, a small molecule that was designed de novo based on naturally occurring host defensins, was investigated for its antiviral activity against these viruses in human small airway epithelial cells (HSAECs) and African green monkey kidney cells (Veros). This testing was further expanded into a non-enveloped Echovirus, a Picornavirus, to further demonstrate brilacidin’s effect on early steps of the viral infectious cycle that leads to inhibition of viral load. Brilacidin demonstrated antiviral activity against alphaviruses VEEV TC-83, VEEV TrD, SINV, EEEV, and bunyavirus RVFV.
The inhibitory potential of brilacidin against the viruses tested in this study was dependent on the dosing strategy which necessitated compound addition pre- and post-infection, with addition only at the post-infection stage not eliciting a robust inhibitory response. The inhibitory activity of brilacidin was only modest in the context of the non-enveloped Picornavirus Echovirus, suggesting brilacidin may be less potent against non-enveloped viruses.
However Brilacidin key feature is to destroy bacterial membranes and enveloped viruses protective outer layer. It also destroys protein spikes. This makes viruses and bacteria extremely vulnerable to common therapeutics such as curcumin.
“Something a simple as yellow mustard combined with Brilacidin will induce self inoculation in the human immune system.”
Curcumin is a powerful Antiviral, Anti Bacterial, Anti Fungal Agent
Morgan R Jennings 1,2, Robin J Parks 1,2,3,4,*
•
• PMCID: PMC7693600PMID: 33142686
Abstract
Curcumin, the primary curcuminoid compound found in turmeric spice, has shown broad activity as an antimicrobial agent, limiting the replication of many different fungi, bacteria and viruses. In this review, we summarize recent studies supporting the development of curcumin and its derivatives as broad-spectrum antiviral agents.
Keywords: curcumin, antiviral, broad-spectrum, phytochemical
1. Introduction
Curcumin (diferuloylmethane) is the primary curcuminoid derived from the rhizome of Curcuma longa plant [1,2], and is typically used both as a strong food dye and consumed as a spice in the form of turmeric [1]. In addition, curcumin has seen wide use in traditional medicine throughout Asia, due to its anti-inflammatory and wound-healing properties [3,4]. Modern research has also demonstrated that curcumin has diverse biological functions, with reported anti-cancer, antioxidant and anti-microbial properties [3,5,6]. Curcumin can act not only as an anti-fungal and anti-bacterial compound, but also as an anti-viral compound, inhibiting replication in a wide-range of viruses [7], as summarized in Table 1. In this review, recent research into the antiviral properties of curcumin, its derivatives, and formulations will be discussed.
Table 1.
Pathways/processes impacted by curcumin and analogues, and their effect on viruses.
Pathway/Process and Antiviral Activity.
Viral entry - Dengue virus, Viral hemorrhagic septicemia virus
Replication - Dengue virus
Anti-inflammation Replication- Human immunodeficiency virus
Antioxidation Replication - Human immunodeficiency virus (HIV)
APE1 redox reactions Replication- Kaposi’s sarcoma-associated herpesvirus
Cell lipogenesis Replication - Dengue virus
Cleavage of eIF4G Protein expression- Enterovirus 71
Conformation of viral/cellular surface proteins Viral attachment - Zika virus, Chikungunya virus, Vesicular stomatitis virus, Human respiratory syncytial virus
HSC71 expression,Viral entry, - Viral hemorrhagic septicemia virus
NF-κB signalling Replication - Influenza A virus
Viral egress- Herpes simplex virus 2
PKCδ phosphorylation Protein expression - Enterovirus 71
ROS production Viricidal - Norovirus
Lipid raft formation - Bovine herpes virus 1
Viral enzymes Viral egress Viral protease - Influenza A virus Dengue virus
Viral proteins Viral entry - Influenza A virus
Porcine reproductive and respiratory syndrome virus
Viral protein degradation - HIV
Viricidal - Norovirus
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