Methylxanthines as Potential Inhibitor of SARS-CoV-2: an In Silico Approach

Rolta, Rajan; Salaria, Deeksha; Sharma, Bhanu; Awofisayo, Oladoja; Fadare, Olatomide A.; Sharma, Sonum; Patel, Chirag; Kumar, Vikas; Sourirajan, Anuradha; Dev, Kamal

doi:10.1007/s40495-021-00276-3

Cited by 19 publications

(12 citation statements)

References 53 publications

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“…As sterols interact with the active site, they can be promising candidates, particularly oxygenous tetrahydroxy sterol, which has a high tendency to form hydrogen bonds. Schiff base ligands have been shown to inhibit M pro in previous studies [ 54 ] as well as caffeine [ 54 , 55 ], nethylxanthines [ 56 ], natural product isolates [ 57 ], glycyrrhizin [ 58 ], ML188 [ 59 ], pyrimidonic and pyridonic pharmaceuticals [ 60 , 61 ], kaempferol [ 62 ], fungal natural products [ 63 ], marine natural compounds [ 64 ], Ceftazidime [ 65 ], hepatitis C virus protease drugs [ 66 ], and other inhibitors [ 67 , 68 , 69 , 70 , 71 , 72 ]. In our molecular docking study, these natural compounds were identified as potential M pro inhibitors.…”

Section: Resultsmentioning

confidence: 99%

Inhibitory Activity of Saussurea costus Extract against Bacteria, Candida, Herpes, and SARS-CoV-2

Idriss

Siddig

González-Maldonado

et al. 2023

Plants

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Medicinal herbs have long been utilized to treat various diseases or to relieve the symptoms of some ailments for extended periods. The present investigation demonstrates the phytochemical profile, molecular docking, anti-Candida activity, and anti-viral activity of the Saussurea costus acetic acid extract. GC-MS analysis of the extract revealed the presence of 69 chemical compounds. The chemical compounds were alkaloids (4%), terpenoids (79%), phenolic compounds (4%), hydrocarbons (7%), and sterols (6%). Molecular docking was used to study the inhibitory activity of 69 identified compounds against SARS-CoV-2. In total, 12 out of 69 compounds were found to have active properties exhibiting SARS-CoV-2 inhibition. The binding scores of these molecules were significantly low, ranging from −7.8 to −5.6 kcal/mol. The interaction of oxatricyclo [20.8.0.0(7,16)] triaconta-1(22),7(16),9,13,23,29-hexaene with the active site is more efficient. Furthermore, the extract exhibited significant antimicrobial activity (in vitro) against Candida albicans, which was the most susceptible microorganism, followed by Bacillus cereus, Salmonella enterica, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, respectively. On the other hand, its antiviral activity was evaluated against HSV-1 and SARS-CoV-2, and the results showed a significant positive influence against HSV-1 (EC50 = 82.6 g/mL; CC50 = 162.9 g/mL; selectivity index = 1.9). In spite of this, no impact could be observed in terms of inhibiting the entry of SARS-CoV-2 in vitro.

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Section: Resultsmentioning

confidence: 99%

Inhibitory Activity of Saussurea costus Extract against Bacteria, Candida, Herpes, and SARS-CoV-2

Idriss

Siddig

González-Maldonado

et al. 2023

Plants

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“…Interestingly, data from an in silico study showed that among 5 methylxanthines tested, theophylline exhibited the best binding affinity for all three target proteins of SARS-CoV-2, the spike protein, main protease, and nucleocapsid protein. This lays the groundwork for future studies of theophylline as an antiviral drug for COVID-19 ( Rolta et al, 2022 ).…”

Section: Bronchodilators As Potential Therapeutic Options For Covid-19mentioning

confidence: 92%

One stone two birds: anti-inflammatory bronchodilators as a potential pharmacological strategy for COVID-19

Fang

Yang

et al. 2023

Front. Pharmacol.

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The ongoing Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed a huge threat to public health across the world. While vaccinations are essential for reducing virus transmission and attenuating disease severity, the nature of high mutation rate of SARS-CoV-2 renders vaccines less effective, urging quick development of effective therapies for COVID-19 disease. However, developing novel drugs remains extremely challenging due to the lengthy process and high cost. Alternatively, repurposing of existing drugs on the market represents a rapid and safe strategy for combating COVID-19 pandemic. Bronchodilators are first line drugs for inflammatory lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Compared to other anti-inflammatory drugs repurposed for COVID-19, bronchodilators are unique in that they have both anti-inflammatory and bronchodilating properties. Whether the dual properties of bronchodilators empower them greater potential to be repurposed for COVID-19 is worth exploring. In fact, clinical and preclinical studies have recently emerged to investigate the benefits of bronchodilators such assalbutamol, formoterol and theophylline in treating COVID-19, and many of them have shown encouraging efficacy on attenuating disease severity of pneumonia and other associated symptoms. To comprehensively understand the latest progress on COVID-19 intervention with bronchodilators, this review will summarize recent findings in this area and highlight the promising clinical benefits and possible adverse effects of bronchodilators as therapeutic options for COVID-19 with a focus on β2 receptor agonists, anticholinergic drugs and theophylline.

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“…Curcumin, piperine, luteolin, phenylnaphthalene, withanolides, anonaine, resveratrol, emodin, anthrarufin, and caffeine are natural immunomodulatory compounds obtained from plant sources known to limit the generation and secretion of inflammatory cytokines/chemokines ( Hamed et al, 2019 ; El-Gengaihi et al, 2020a ; Rolta et al, 2021a ; Rolta et al, 2021b ; Mohammed et al, 2022b ; Mohammed et al, 2022c ; Rolta et al, 2022 ). This inhibitory impact is mediated through analysis and planning involved in the generation and release of cytokines and chemokines (e.g., NF-κB, JAK/STAT, and MAPK/ERK).…”

Section: Natural Immunosuppressants As Adjuvants In Managing Covid-19...mentioning

confidence: 99%

Fighting cytokine storm and immunomodulatory deficiency: By using natural products therapy up to now

Mohammed

2023

Front. Pharmacol.

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A novel coronavirus strain (COVID-19) caused severe illness and mortality worldwide from 31 December 2019 to 21 March 2023. As of this writing, 761,071,826 million cases have been diagnosed worldwide, with 6,879,677 million deaths accorded by WHO organization and has spread to 228 countries. The number of deaths is closely connected to the growth of innate immune cells in the lungs, mainly macrophages, which generate inflammatory cytokines (especially IL-6 and IL-1β) that induce “cytokine storm syndrome” (CSS), multi-organ failure, and death. We focus on promising natural products and their biologically active chemical constituents as potential phytopharmaceuticals that target virus-induced pro-inflammatory cytokines. Successful therapy for this condition is currently rare, and the introduction of an effective vaccine might take months. Blocking viral entrance and replication and regulating humoral and cellular immunity in the uninfected population are the most often employed treatment approaches for viral infections. Unfortunately, no presently FDA-approved medicine can prevent or reduce SARS-CoV-2 access and reproduction. Until now, the most important element in disease severity has been the host’s immune response activation or suppression. Several medicines have been adapted for COVID-19 patients, including arbidol, favipiravir, ribavirin, lopinavir, ritonavir, hydroxychloroquine, chloroquine, dexamethasone, and anti-inflammatory pharmaceutical drugs, such as tocilizumab, glucocorticoids, anakinra (IL-1β cytokine inhibition), and siltuximab (IL-6 cytokine inhibition). However, these synthetic medications and therapies have several side effects, including heart failure, permanent retinal damage in the case of hydroxyl-chloroquine, and liver destruction in the case of remdesivir. This review summarizes four strategies for fighting cytokine storms and immunomodulatory deficiency induced by COVID-19 using natural product therapy as a potential therapeutic measure to control cytokine storms.

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Methylxanthines as Potential Inhibitor of SARS-CoV-2: an In Silico Approach

Cited by 19 publications

References 53 publications

Inhibitory Activity of Saussurea costus Extract against Bacteria, Candida, Herpes, and SARS-CoV-2

Inhibitory Activity of Saussurea costus Extract against Bacteria, Candida, Herpes, and SARS-CoV-2

One stone two birds: anti-inflammatory bronchodilators as a potential pharmacological strategy for COVID-19

Fighting cytokine storm and immunomodulatory deficiency: By using natural products therapy up to now

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