Targeting Neurological Manifestations of Coronaviruses by Candidate Phytochemicals: A Mechanistic Approach

Fakhri, Sajad; Piri, Sana; Majnooni, Mohammad Bagher; Farzaei, Mohammad Hosein; Echeverría, Javier

doi:10.3389/fphar.2020.621099

Cited by 20 publications

(19 citation statements)

References 266 publications

(339 reference statements)

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“…The present study shows that alkaloids, as one of the most widespread natural compounds, hold out the hope for an effective treatment against COVID-19, due to their simultaneous effects on several therapeutic targets with prominent antiviral effects. Hence, marine/plant-derived alkaloids such as berberine, tetrandrine, cepharanthine, lycorine, ergotamine, crambescidin 786, palmatine, noscapine, and quinine with prominent anti-SARS-CoV-2 effects along with antipyretic, anti-inflammatory, antitussive and lung injury, immunomodulatory, and protective effects against neurotoxicity, cardiotoxicity, nephrotoxicity, and hepatotoxicity could be promising candidates for COVID-19 treatment [ 46 , 48 , 52 , 64 , 68 , 76 , 77 , 79 , 82 , 93 ]. Therefore, according to the contents mentioned, extensive and comprehensive clinical studies on these compounds seem to be useful and necessary.…”

Section: Discussionmentioning

confidence: 99%

“…In their study, inhibition of nucleotide biosynthesis was suggested for the aforementioned antiviral effects [ 51 ]. In addition to its anti-SARS-CoV-2 effects, lycorine also has prominent neuroprotective effects that can play a multifaceted role in the treatment of this disease due to the neurological complications of COVID-19 disease [ 52 , 53 ]. Consequently, Bleasel and Peterson published a commentary on the potential of emetine and ipecac alkaloids as anti-SARS-CoV-2 agents [ 54 ].…”

Section: Alkaloids As Potential Phytochemicals Against Sars-cov-2mentioning

confidence: 99%

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Alkaloids as Potential Phytochemicals against SARS-CoV-2: Approaches to the Associated Pivotal Mechanisms

Majnooni

Fakhri

Bahrami

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Since its inception, the coronavirus disease 2019 (COVID-19) pandemic has infected millions of people around the world. Therefore, it is necessary to find effective treatments against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), as it is the viral source of COVID-19. Alkaloids are one of the most widespread plant-derived natural compounds with prominent antiviral effects. Accordingly, these phytochemicals have been promising candidates towards discovering effective treatments for COVID-19. Alkaloids have shown potential anti-SARS-CoV activities via inhibiting pathogenesis-associated targets of the Coronaviridae family that are required for the virus life cycle. In the current study, the chemistry, plant sources, and antiviral effects of alkaloids, as well as their anti-SARS-CoV-2 effect with related mechanisms, are reviewed towards discovering an effective treatment against COVID-19.

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Section: Discussionmentioning

confidence: 99%

Section: Alkaloids As Potential Phytochemicals Against Sars-cov-2mentioning

confidence: 99%

Alkaloids as Potential Phytochemicals against SARS-CoV-2: Approaches to the Associated Pivotal Mechanisms

Majnooni

Fakhri

Bahrami

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…The potential of phytochemicals in demonstrating antiviral effects through inhibiting the viral life cycle indicates a promising future to find novel antiviral lead compounds against neuronal signs of emerging viral diseases. Previously, we have analyzed the capability of these phytochemicals in passing BBB towards neuroprotective responses ( Fakhri et al, 2020b ), which showed hopeful results for most plant-derived secondary metabolites in modulating the aforementioned dysregulated pathways in CNS. Additionally, to drawback, the pharmacokinetic limitation of phytochemicals, novel drug delivery systems, could pave the road towards neuroprotection against emerging viral diseases.…”

Section: Discussionmentioning

confidence: 99%

“…Recently scientists investigated the effects of natural products on emerging infectious diseases, including the influenza virus, DENV, Zika, and EBOV ( Zheng et al, 2021 ). Considering the common dysregulated pathophysiological mechanisms of emerging infectious diseases and the capability of some phytochemicals in passing BBB ( Fakhri et al, 2020b ) urge the need to introduce candidate phytochemicals as potential modulators of peripheral complications, extrapolated to the same dysregulations in CNS.…”

Section: Phytochemicals Against Emerging Infectious Diseases: Mechanistic Approaches To Neurological Signsmentioning

confidence: 99%

Modulating Neurological Complications of Emerging Infectious Diseases: Mechanistic Approaches to Candidate Phytochemicals

et al. 2021

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Growing studies are revealing the critical manifestations of influenza, dengue virus (DENV) infection, Zika virus (ZIKV) disease, and Ebola virus disease (EVD) as emerging infectious diseases. However, their corresponding mechanisms of major complications headed for neuronal dysfunction are not entirely understood. From the mechanistic point of view, inflammatory/oxidative mediators are activated during emerging infectious diseases towards less cell migration, neurogenesis impairment, and neuronal death. Accordingly, the virus life cycle and associated enzymes, as well as host receptors, cytokine storm, and multiple signaling mediators, are the leading players of emerging infectious diseases. Consequently, chemokines, interleukins, interferons, carbohydrate molecules, toll-like receptors (TLRs), and tyrosine kinases are leading orchestrates of peripheral and central complications which are in near interconnections. Some of the resulting neuronal manifestations have attracted much attention, including inflammatory polyneuropathy, encephalopathy, meningitis, myelitis, stroke, Guillain-Barré syndrome (GBS), radiculomyelitis, meningoencephalitis, memory loss, headaches, cranial nerve abnormalities, tremor, and seizure. The complex pathophysiological mechanism behind the aforementioned complications urges the need for finding multi-target agents with higher efficacy and lower side effects. In recent decades, the natural kingdom has been highlighted as promising neuroprotective natural products in modulating several dysregulated signaling pathways/mediators. The present study provides neuronal manifestations of some emerging infectious diseases and underlying pathophysiological mechanisms. Besides, a mechanistic-based strategy is developed to introduce candidate natural products as promising multi-target agents in combating major dysregulated pathways towards neuroprotection in influenza, DENV infection, ZIKV disease, and EVD.

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“…TBI induced mitochondrial neuronal damage, as evidenced by an increase in ROS mitochondria and a reduction in MMP, causing the previous mitochondrial transition pore to open [ 69 ]. Polydatin has shown various pharmacological benefits, including antioxidation, anti-inflammation, anti-apoptosis, and brain-associated injuries [ 71 , 72 ].…”

Section: Polydatin Against Nddsmentioning

confidence: 99%

The Neuroprotective Role of Polydatin: Neuropharmacological Mechanisms, Molecular Targets, Therapeutic Potentials, and Clinical Perspective

et al. 2021

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Neurodegenerative diseases (NDDs) are one of the leading causes of death and disability in humans. From a mechanistic perspective, the complexity of pathophysiological mechanisms contributes to NDDs. Therefore, there is an urgency to provide novel multi-target agents towards the simultaneous modulation of dysregulated pathways against NDDs. Besides, their lack of effectiveness and associated side effects have contributed to the lack of conventional therapies as suitable therapeutic agents. Prevailing reports have introduced plant secondary metabolites as promising multi-target agents in combating NDDs. Polydatin is a natural phenolic compound, employing potential mechanisms in fighting NDDs. It is considered an auspicious phytochemical in modulating neuroinflammatory/apoptotic/autophagy/oxidative stress signaling mediators such as nuclear factor-κB (NF-κB), NF-E2–related factor 2 (Nrf2)/antioxidant response elements (ARE), matrix metalloproteinase (MMPs), interleukins (ILs), phosphoinositide 3-kinases (PI3K)/protein kinase B (Akt), and the extracellular regulated kinase (ERK)/mitogen-activated protein kinase (MAPK). Accordingly, polydatin potentially counteracts Alzheimer’s disease, cognition/memory dysfunction, Parkinson’s disease, brain/spinal cord injuries, ischemic stroke, and miscellaneous neuronal dysfunctionalities. The present study provides all of the neuroprotective mechanisms of polydatin in various NDDs. Additionally, the novel delivery systems of polydatin are provided regarding increasing its safety, solubility, bioavailability, and efficacy, as well as developing a long-lasting therapeutic concentration of polydatin in the central nervous system, possessing fewer side effects.

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Targeting Neurological Manifestations of Coronaviruses by Candidate Phytochemicals: A Mechanistic Approach

Cited by 20 publications

References 266 publications

Alkaloids as Potential Phytochemicals against SARS-CoV-2: Approaches to the Associated Pivotal Mechanisms

Alkaloids as Potential Phytochemicals against SARS-CoV-2: Approaches to the Associated Pivotal Mechanisms

Modulating Neurological Complications of Emerging Infectious Diseases: Mechanistic Approaches to Candidate Phytochemicals

The Neuroprotective Role of Polydatin: Neuropharmacological Mechanisms, Molecular Targets, Therapeutic Potentials, and Clinical Perspective

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