Crosstalk between endoplasmic reticulum stress and anti-viral activities: A novel therapeutic target for COVID-19

Banerjee, Aditi; Czinn, Steven J.; Reíter, Russel J.; Blanchard, Thomas G.

doi:10.1016/j.lfs.2020.117842

Cited by 100 publications

(83 citation statements)

References 85 publications

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“…Changing the administration route might increase the bioavailability of a compound. For example, the bioavailability of an anti-inflammatory compound, andrographolide, is increased when it is administered intravenously instead of through oral administration ( 295 ). Other methods to enhance the bioavailability of target compound include using drug delivery systems, the nano-formulation of a drug, using adjuvant systems, or altering structural analogs ( 220 , 296 ).…”

Section: Drug Discovery From Psms: Addressing the Major Challenges Tomentioning

confidence: 99%

Plants Metabolites: Possibility of Natural Therapeutics Against the COVID-19 Pandemic

et al. 2020

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COVID-19, a disease induced by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2), has been the cause of a worldwide pandemic. Though extensive research works have been reported in recent days on the development of effective therapeutics against this global health crisis, there is still no approved therapy against SARS-CoV-2. In the present study, plant-synthesized secondary metabolites (PSMs) have been prioritized to make a review focusing on the efficacy of plant-originated therapeutics for the treatment of COVID-19. Plant metabolites are a source of countless medicinal compounds, while the diversity of multidimensional chemical structures has made them superior to treat serious diseases. Some have already been reported as promising alternative medicines and lead compounds for drug repurposing and discovery. The versatility of secondary metabolites may provide novel antibiotics to tackle MDR (Multi-Drug Resistant) microbes too. This review attempted to find out plant metabolites that have the therapeutic potential to treat a wide range of viral pathogens. The study includes the search of remedies belonging to plant families, susceptible viral candidates, antiviral assays, and the mode of therapeutic action; this attempt resulted in the collection of an enormous number of natural therapeutics that might be suggested for the treatment of COVID-19. About 219 plants from 83 families were found to have antiviral activity. Among them, 149 plants from 71 families were screened for the identification of the major plant secondary metabolites (PSMs) that might be effective for this pandemic. Our investigation revealed that the proposed plant metabolites can serve as potential anti- SARS-CoV-2 lead molecules for further optimization and drug development processes to combat COVID-19 and future pandemics caused by viruses. This review will stimulate further analysis by the scientific community and boost antiviral plant-based research followed by novel drug designing.

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Section: Drug Discovery From Psms: Addressing the Major Challenges Tomentioning

confidence: 99%

Plants Metabolites: Possibility of Natural Therapeutics Against the COVID-19 Pandemic

et al. 2020

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“…Melatonin is a naturally occurring molecule assumed to be present in every species [ 19 ]. Due to its antioxidant, anti-inflammatory, as well as other properties [ 20 , 21 , 22 , 23 , 24 , 25 ], it has been speculated to be a promising molecule for treating COVID-19 patients [ 18 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ], and also other deadly viral infectious diseases [ 48 , 49 , 50 , 51 ]. A small scale clinical trial has also shown promising results [ 52 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting Host Defense System and Rescuing Compromised Mitochondria to Increase Tolerance against Pathogens by Melatonin May Impact Outcome of Deadly Virus Infection Pertinent to COVID-19

Tan¹,

Hardeland

2020

Molecules

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Fighting infectious diseases, particularly viral infections, is a demanding task for human health. Targeting the pathogens or targeting the host are different strategies, but with an identical purpose, i.e., to curb the pathogen’s spreading and cure the illness. It appears that targeting a host to increase tolerance against pathogens can be of substantial advantage and is a strategy used in evolution. Practically, it has a broader protective spectrum than that of only targeting the specific pathogens, which differ in terms of susceptibility. Methods for host targeting applied in one pandemic can even be effective for upcoming pandemics with different pathogens. This is even more urgent if we consider the possible concomitance of two respiratory diseases with potential multi-organ afflictions such as Coronavirus disease 2019 (COVID-19) and seasonal flu. Melatonin is a molecule that can enhance the host’s tolerance against pathogen invasions. Due to its antioxidant, anti-inflammatory, and immunoregulatory activities, melatonin has the capacity to reduce the severity and mortality of deadly virus infections including COVID-19. Melatonin is synthesized and functions in mitochondria, which play a critical role in viral infections. Not surprisingly, melatonin synthesis can become a target of viral strategies that manipulate the mitochondrial status. For example, a viral infection can switch energy metabolism from respiration to widely anaerobic glycolysis even if plenty of oxygen is available (the Warburg effect) when the host cell cannot generate acetyl-coenzyme A, a metabolite required for melatonin biosynthesis. Under some conditions, including aging, gender, predisposed health conditions, already compromised mitochondria, when exposed to further viral challenges, lose their capacity for producing sufficient amounts of melatonin. This leads to a reduced support of mitochondrial functions and makes these individuals more vulnerable to infectious diseases. Thus, the maintenance of mitochondrial function by melatonin supplementation can be expected to generate beneficial effects on the outcome of viral infectious diseases, particularly COVID-19.

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“…Similarly, we posit that new vulnerabilities in the regulatory and metabolic networks of a virus-infected cell can be targeted with drugs that will have no cytotoxicity to uninfected cells. Common transcriptional responses of virally infected cells include innate immune responses as well as cellular stress responses such as the unfolded protein response, which may suggest specific targets for host-directed antivirals that can be designed to either selectively disable infected cells or support antiviral activity of the innate cellular, and perhaps the coupled adaptive immune, response to infection (Banerjee et al, 2020;Ferreira et al, 2020;Netea et al, 2020).…”

Section: Mast Et Almentioning

confidence: 99%

Crippling life support for SARS-CoV-2 and other viruses through synthetic lethality

Mast

Navare

Sloot

et al. 2020

Journal of Cell Biology

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With the rapid global spread of SARS-CoV-2, we have become acutely aware of the inadequacies of our ability to respond to viral epidemics. Although disrupting the viral life cycle is critical for limiting viral spread and disease, it has proven challenging to develop targeted and selective therapeutics. Synthetic lethality offers a promising but largely unexploited strategy against infectious viral disease; as viruses infect cells, they abnormally alter the cell state, unwittingly exposing new vulnerabilities in the infected cell. Therefore, we propose that effective therapies can be developed to selectively target the virally reconfigured host cell networks that accompany altered cellular states to cripple the host cell that has been converted into a virus factory, thus disrupting the viral life cycle.

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Crosstalk between endoplasmic reticulum stress and anti-viral activities: A novel therapeutic target for COVID-19

Cited by 100 publications

References 85 publications

Plants Metabolites: Possibility of Natural Therapeutics Against the COVID-19 Pandemic

Plants Metabolites: Possibility of Natural Therapeutics Against the COVID-19 Pandemic

Targeting Host Defense System and Rescuing Compromised Mitochondria to Increase Tolerance against Pathogens by Melatonin May Impact Outcome of Deadly Virus Infection Pertinent to COVID-19

Crippling life support for SARS-CoV-2 and other viruses through synthetic lethality

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