Computationally Repurposed Natural Products Targeting SARS-CoV-2 Attachment and Entry Mechanisms

Quimque, Mark Tristan J.; Notarte, Kin Israel; Leon, Von Novi O. de; Manzano, Joe Anthony; Muñoz, John Emmanuel R.; Pilapil, Delfin Yñigo H.; Lim, Justin Allen K.; Macabeo, Allan Patrick G.

doi:10.1007/978-3-031-08045-6_25

Cited by 5 publications

(5 citation statements)

References 91 publications

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“…According to several studies, sterol compounds act as cancer inhibitors, anti-inflammatory medications, immunomodulatory agents, and antiviral agents [ 49 , 50 ]. Various investigations have shown that terpenoids have a high proclivity for acting as SARS-CoV-2 blockers [ 51 ]. Based on a new study integrating quantum chemistry, molecular docking, and dynamic dynamics, phenolic chemicals have potential therapeutic implications for SARS-CoV-2.…”

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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“…Visualization and analysis of the enzyme–ligand complex conformation were carried out using ChimeraX and Biovia Discovery Studios (version 4.1) . Validation of the docking protocol was done by extracting the bound co-crystallized ligand and re-docking it to the set grid. ,,, …”

Section: Methodsmentioning

confidence: 99%

“…54 Validation of the docking protocol was done by extracting the bound co-crystallized ligand and re-docking it to the set grid. 20 , 40 , 54 , 55 …”

Section: Methodsmentioning

confidence: 99%

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Attenuation of Lipopolysaccharide-Induced Inflammatory Responses through Inhibition of the NF-κB Pathway and the Increased NRF2 Level by a Flavonol-Enriched n-Butanol Fraction from Uvaria alba

et al. 2023

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Pathologic hyperreactive inflammatory responses occur when there is excessive activation of a proinflammatory NF-κB pathway and a reduced cytoprotective NRF2 cascade. The noncytotoxic, highly selective COX-2 inhibitory flavonol-enriched butanol fraction (UaB) from Uvaria alba (U. alba) was investigated for its inflammatory modulating potential by targeting NF-κB activation and NRF2 activity. Enzyme-linked immunosorbent assay was initially performed to measure levels of proinflammatory mediators [nitric oxide (NO), prostaglandin E2, and reactive oxygen species (ROS)] and cytokines [tumor necrosis factor-alpha (TNF-α), IL-1β, and IL-6], followed by reverse transcription-polymerase chain reaction and western blotting to determine mRNA and protein expression, respectively. Using immunofluorescence staining combined with western blot analysis, the activation of NF-κB was further investigated. NRF2 activity was also measured using a luciferase reporter assay. UaB abrogated protein and mRNA expressions of inducible nitric oxide synthase (iNOS), COX-2, TNF-α, IL-1β, and IL-6 in RAW 264.7 macrophages, thereby suppressing the production of proinflammatory mediators and cytokines. This was further validated when a concentration-dependent decrease in NO and ROS production was observed in zebrafish (Danio rerio) larvae. UaB also increased NRF2 activity in HaCaT/ARE cell line and attenuated NF-κB activation by inhibiting the nuclear translocation of transcription factor p65 in RAW 264.7 macrophages. Nontargeted LC–MS analysis of UaB revealed the presence of the flavonols quercitrin (1), quercetin (2), rutin (3), kaempferol (4), and kaempferol 3-O-rutinoside (5). Molecular docking indicates that major flavonol aglycones have high affinity toward COX-2 NSAID-binding sites, TNF-α, and TNF-α converting enzyme, while the glycosylated flavonoids showed strong binding toward iNOS and IKKall possessing dynamic stability when performing molecular dynamics simulations at 140 ns. This is the first report to have elucidated the mechanistic anti-inflammatory potential of the Philippine endemic plant U. alba.

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“…Sesquiterpenes are the most abundant compounds in S. lappa, with costunolide and dehydrocostus lactone being the main active ingredients [22,23]. Multiple investigations have demonstrated that terpenoids tend to function as inhibitors of SARS-CoV-2 [24]. The myrcene compound present in S. lappa impacts the ACE-2 receptor, hence impeding the entry of SARS-CoV-2 into the host cells [25].…”

Section: Discussionmentioning

confidence: 99%

Antiviral Activity of Saussurea Lappa Ethanol Extract Against Sars-Cov-2: In Vitro Study

FITRIANINGSIH,

SANTOSANINGSIH,

DJAJALAKSANA

et al. 2024

Int J App Pharm

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Objective: The study aims to investigate the antiviral activity of S. lappa against Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) in vitro. Methods: The extracts are obtained by ultrasonic-assisted extraction (UAE) with a 96% ethanol solvent. Thin-layer chromatography (TLC) uses n-hexane: ethyl acetate and chloroform: methanol) as mobile phases. The staining outcome is subsequently examined using UV visualizers with a wavelength of 366 nm. To assess the antiviral activity of Vero E6 cells, extracts were employed at doses of 25, 50, 75, and 100 µg/ml, with remdesivir serving as the positive control. Supernatants were collected on days 1, 2, 3, and 6 for qRT-PCR testing with target genes E and ORF1ab. Time-addition experiments were conducted to determine how the extract works as antiviral. Protein expression was tested with Western blots with antibodies S and N SARS-CoV-2. Results: TLC identifies terpenoid chemicals present in the ethanol extract of S. lappa. The ethanol extract of S. lappa exhibited antiviral effects against SARS-CoV-2, with an inhibitory concentration 50 (IC50) of 40 µg/ml, a cytotoxic concentration 50 (CC50) of 131.4 µg/ml, and a selectivity index of 3.51. The extract can potentially impact the entry-post-entry phase of SARS-CoV-2 infection in Vero cells. The immunoblotting results demonstrated a reduction in the expression of S and N proteins in the treatment group compared to the negative control. Conclusion: S. lappa ethanol extract has antiviral activity against SARS-CoV-2 based on an in vitro study.

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Computationally Repurposed Natural Products Targeting SARS-CoV-2 Attachment and Entry Mechanisms

Cited by 5 publications

References 91 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

Attenuation of Lipopolysaccharide-Induced Inflammatory Responses through Inhibition of the NF-κB Pathway and the Increased NRF2 Level by a Flavonol-Enriched n-Butanol Fraction from Uvaria alba

Antiviral Activity of Saussurea Lappa Ethanol Extract Against Sars-Cov-2: In Vitro Study

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