The Discovery of Naringenin as Endolysosomal Two-Pore Channel Inhibitor and Its Emerging Role in SARS-CoV-2 Infection

D’Amore, Antonella; Gradogna, Antonella; Palombi, Fioretta; Minicozzi, Velia; Ceccarelli, Matteo; Carpaneto, Armando; Filippini, Antonio

doi:10.3390/cells10051130

Cited by 22 publications

(14 citation statements)

References 98 publications

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“… 41 , 42 Moreover, naringin of citrus fruits has been shown to suppress the expression of proinflammatory cytokines during the inflammatory response. 41 , 43 Furthermore, hesperidin, a biologically active molecule in orange fruit, was shown to inactivate the SARS-CoV-2 RNA polymerase complex. 44 , 45 The antioxidant components of citrus fruits can also protect against oxidative stress associated with COVID-19 infection.…”

Section: Discussionmentioning

confidence: 99%

Effect of natural products use prior to infection with COVID-19 on disease severity and hospitalization: A self-reported cross-sectional survey study

et al. 2022

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Background: Managing coronavirus disease 2019 (COVID-19) using available resources is essential to reduce the health burden of disease. The severity of COVID-19 is affected by nutritional status. In this study the effect of natural product use prior to infection with COVID-19 on disease severity and hospitalization was explored. Methods: This was a cross-sectional study. Between March and July 2021, a self-administered survey was conducted in Jordan. Individuals who recovered from COVID-19 and were ≥18 years old were the study population. Study measures included the use of natural products, COVID-19 severity, and hospitalization status. A multivariate regression model was used for statistical analysis. Results: The mean age (mean ± SD) of the study sample (n=2,148) was 40.25 ± 15.58 years old. Multivariate logistic regression showed that the regular intake of carnation (OR [0.56], CI [0.37–0.85]), onion (OR [0.69], CI [0.52–0.92]), lemon (OR [0.68], CI [0.51–0.90]), and citrus fruits (OR [0.66], CI [0.50–0.89]) before infection were associated with a substantial reduction in COVID-19 severity (P<0.01). Also, the consumption of carnation (OR [0.55], CI [0.34–0.88]), lemon (OR [0.57], CI [0.42–0.78]), and citrus fruits (OR [0.61], CI [0.44–0.84]) were associated with a significant decrease in the frequency of COVID-19-induced hospitalization (P<0.01). Conclusions: Regular consumption of carnation, lemon, and citrus fruits before infection was associated with better outcomes for COVID-19. Studies on other populations are required to confirm these findings.

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Section: Discussionmentioning

confidence: 99%

Effect of natural products use prior to infection with COVID-19 on disease severity and hospitalization: A self-reported cross-sectional survey study

et al. 2022

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“…TPCs (Two Pore Channels) are cation channels involved in Ca 2+ signalling and activated by the ligands NAADP and PI(3,5)P 2 [24][25][26][27][28]. TPC proteins may be possible drug targets for the treatment of Ebola and SARS-CoV-2 viruses infection, since they control virus entry into the host cell [13,14,29,30]. Moreover, TPCs have been shown to be involved in neurodegenerative Parkinson's disease [31] and in processes of neoangiogenesis [32][33][34].…”

Section: Main Families Of Lysosomal Channels and Transportersmentioning

confidence: 99%

Current Methods to Unravel the Functional Properties of Lysosomal Ion Channels and Transporters

Festa

Minicozzi

Boccaccio

et al. 2022

Cells

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A distinct set of channels and transporters regulates the ion fluxes across the lysosomal membrane. Malfunctioning of these transport proteins and the resulting ionic imbalance is involved in various human diseases, such as lysosomal storage disorders, cancer, as well as metabolic and neurodegenerative diseases. As a consequence, these proteins have stimulated strong interest for their suitability as possible drug targets. A detailed functional characterization of many lysosomal channels and transporters is lacking, mainly due to technical difficulties in applying the standard patch-clamp technique to these small intracellular compartments. In this review, we focus on current methods used to unravel the functional properties of lysosomal ion channels and transporters, stressing their advantages and disadvantages and evaluating their fields of applicability.

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“…In TPC2-silenced Huh7.5 cells (silenced with siRNA), infection with the coronavirus HCoV 229E was inhibited significantly compared to the control, which indicates that TPC2 plays an active role in coronavirus infection. Since naringenin can inhibit TPC2, it has been proposed that TPC2 can be the molecular target of the compound [117].…”

Section: Flavonoids-classification Structure and Anti-viral Activitiesmentioning

confidence: 99%

Nanotechnology Applications of Flavonoids for Viral Diseases

et al. 2021

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Recent years have witnessed the emergence of several viral diseases, including various zoonotic diseases such as the current pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Other viruses, which possess pandemic-causing potential include avian flu, Ebola, dengue, Zika, and Nipah virus, as well as the re-emergence of SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome) coronaviruses. Notably, effective drugs or vaccines against these viruses are still to be discovered. All the newly approved vaccines against the SARS-CoV-2-induced disease COVID-19 possess real-time possibility of becoming obsolete because of the development of ‘variants of concern’. Flavonoids are being increasingly recognized as prophylactic and therapeutic agents against emerging and old viral diseases. Around 10,000 natural flavonoid compounds have been identified, being phytochemicals, all plant-based. Flavonoids have been reported to have lesser side effects than conventional anti-viral agents and are effective against more viral diseases than currently used anti-virals. Despite their abundance in plants, which are a part of human diet, flavonoids have the problem of low bioavailability. Various attempts are in progress to increase the bioavailability of flavonoids, one of the promising fields being nanotechnology. This review is a narrative of some anti-viral dietary flavonoids, their bioavailability, and various means with an emphasis on the nanotechnology system(s) being experimented with to deliver anti-viral flavonoids, whose systems show potential in the efficient delivery of flavonoids, resulting in increased bioavailability.

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The Discovery of Naringenin as Endolysosomal Two-Pore Channel Inhibitor and Its Emerging Role in SARS-CoV-2 Infection

Cited by 22 publications

References 98 publications

Effect of natural products use prior to infection with COVID-19 on disease severity and hospitalization: A self-reported cross-sectional survey study

Effect of natural products use prior to infection with COVID-19 on disease severity and hospitalization: A self-reported cross-sectional survey study

Current Methods to Unravel the Functional Properties of Lysosomal Ion Channels and Transporters

Nanotechnology Applications of Flavonoids for Viral Diseases

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