Screening of Natural Products Inhibitors of SARS-CoV-2 Entry

González-Maldonado, Pamela; Alvarenga, Nelson; Burgos-Edwards, Alberto; Flores-Giubi, Ma. Eugenia; Barúa, Javier; Romero-Rodríguez, M. Cristina; Soto-Rifo, Ricardo; Valiente-Echeverría, Fernando; Langjahr, Patricia; Cantero-González, Guadalupe; Sotelo, Pablo H.

doi:10.3390/molecules27051743

Cited by 26 publications

(21 citation statements)

References 40 publications

(48 reference statements)

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“…To determine the antiviral activity against SARS-CoV-2, the inhibitory activity was evaluated using the pseudovirus method. This system allows for the study of inhibitors of virus entry into the cell [ 54 ]. The antiviral activity was performed using a pseudovirus with Spike proteins from the D614G variant and the VOC variants Gamma and Delta.…”

Section: Resultsmentioning

confidence: 99%

“…The assay was performed in HEK293-ACE2 cells as previously described [ 54 ]. Briefly, 1 × 10 4 cells in suspension were added to each well of 96-well plates and infected in the presence of 2 mg/mL of the extract.…”

Section: Methodsmentioning

confidence: 99%

“…For the post-entry condition, the viral inoculum was added and incubated for 1 h at 37 °C, washed with PBS, and DMEM 2% with the extract was added. After 72 h, the virus genome in the supernatant was quantitated by qPCR, and the antiviral activity was quantified as previously described [ 54 ].…”

Section: Methodsmentioning

confidence: 99%

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Phytochemical Discrimination, Biological Activity and Molecular Docking of Water-Soluble Inhibitors from Saussurea costus Herb against Main Protease of SARS-CoV-2

et al. 2022

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Siddha medicine is one of the oldest medical systems in the world and is believed to have originated more than 10,000 years ago and is prevalent across ancient Tamil land. It is undeniable that inhibitor preferences rise with increasing solubility in water due to the considerations pertaining to the bioavailability and the ease of which unabsorbed residues can be disposed of. In this study, we showed the phytochemical discrimination of Saussurea costus extracted with water at room temperature as a green extraction procedure. A total of 48 compounds were identified using gas chromatography-mass spectrometry (GC-MS). The fatty acids had a high phytochemical abundance at 73.8%, followed by tannins at 8.2%, carbohydrates at 6.9%, terpenoids at 4.3%, carboxylic acids at 2.5%, hydrocarbons at 2.4%, phenolic compounds at 0.2%, and sterols at 1.5%. Of these compounds, 22 were docked on the active side and on the catalytic dyad of His41 and Cys145 of the main protease of SARS-CoV-2 (Mpro). Eight active inhibitors were carbohydrates, five were fatty acids, three were terpenoids, two were carboxylic acids, one was a tannin, one was a phenolic compound, and one was a sterol. The best inhibitors were 4,8,13-Cyclotetradecatriene-1,3-diol, 1,5,9-trimethyl-12-(1-methylethyl), Andrographolide, and delta.4-Androstene-3.beta.,17.beta.-diol, with a binding affinity that ranged from −6.1 kcal/mol to −6.5 kcal/mol. The inhibitory effect of Saussurea costus of SARS-CoV-2 entry into the cell was studied using a pseudovirus with Spike proteins from the D614G variant and the VOC variants Gamma and Delta. Based on the viral cycle of SARS-CoV-2, our results suggest that the Saussurea costus aqueous extract has no virucidal effect and inhibits the virus in the events after cell entry. Furthermore, the biological activity of the aqueous extract was investigated against HSV-1 virus and two bacterial strains, namely Staphylococcus aureus ATCC BAA 1026 and Escherichia coli ATCC 9637. According to this study, an enormous number of water-soluble inhibitors were identified from Saussurea costus against the Mpro, and this is unprecedented as far as we know.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Phytochemical Discrimination, Biological Activity and Molecular Docking of Water-Soluble Inhibitors from Saussurea costus Herb against Main Protease of SARS-CoV-2

et al. 2022

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“…The SARS-CoV-2 spike-pseudotyped virus system has provided a convenient method to screen compound libraries for potential hits that block SARS-CoV-2 entry [ 23 , 26 , 27 , 28 , 29 ]. Many of the positive hits were showing moderate potency.…”

Section: Discussionmentioning

confidence: 99%

Quinolizidines as Novel SARS-CoV-2 Entry Inhibitors

Huang

Zhu

Xie

et al. 2022

IJMS

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COVID-19, caused by the highly transmissible severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has rapidly spread and become a pandemic since its outbreak in 2019. We have previously discovered that aloperine is a new privileged scaffold that can be modified to become a specific antiviral compound with markedly improved potency against different viruses, such as the influenza virus. In this study, we have identified a collection of aloperine derivatives that can inhibit the entry of SARS-CoV-2 into host cells. Compound 5 is the most potent tested aloperine derivative that inhibited the entry of SARS-CoV-2 (D614G variant) spike protein-pseudotyped virus with an IC50 of 0.5 µM. The compound was also active against several other SARS-CoV-2 variants including Delta and Omicron. Results of a confocal microscopy study suggest that compound 5 inhibited the viral entry before fusion to the cell or endosomal membrane. The results are consistent with the notion that aloperine is a privileged scaffold that can be used to develop potent anti-SARS-CoV-2 entry inhibitors.

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“…Scientists are digging into nature to harness the "goldmine" of healing molecules to meet various unmet medical treatment needs. Natural products continue to be major sources of prototypes of antimicrobial and antiviral drugs (Adalja and Inglesby, 2019) and represent viable sources of therapeutic alternatives for many diseases (González-Maldonado et al, 2022). It is estimated that over 70% of all existing pharmaceutical products are of natural product origin (Wangchuk, 2018;Abd et al, 2019).…”

Section: Traditional Drug Discovery Approachmentioning

confidence: 99%

The challenges and opportunities for the development of COVID-19 therapeutics and preparing for the next pandemic

Ogbadoyi

Umar²

2022

Front. Drug. Discov.

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The disease which is today known as COVID-19 is caused by severe acute respiratory. Syndrome coronavirus 2 (SARS-COV-2), was first reported in Wuhan, China in December 2019. The disease has claimed well over six million lives from over 500 million cases. Vaccine hesitancy militates against successful mass vaccination. There is the rapid emergence of new SARS-COV-2 variants, constituting a challenge to the effectiveness of vaccines. Moreover, none of the available vaccines offers 100% protection and even the protection offered is of short duration necessitating booster doses to be taken. Moving forward, the development of plant-based edible vaccines will be a remarkable strategic approach to overcome vaccine hesitancy and improve vaccine uptake. So far only about nine drugs for COVID-19 treatment have approvals by either or both the European Medicines Agency and the FDA. While drug repurposing to address the emerging need in the early period of the COVID-19 pandemic has been contextually very useful, investment in it remains relatively low for commercial reasons arising from patenting issues. Embarking on new drug discovery and development strategies targeting both the virus and host factors is a very appealing option. Targeting druggable targets that are present across viruses, particularly the coronaviruses, for drug discovery and development represents an important strategy for pandemic preparedness. Natural products are an important reservoir of chemical scaffolds with huge potential for the discovery of novel chemical entities for development of novel therapeutics. Phytopharming is an available technology that can be used for mass and accelerated production of therapeutic molecules that will be required within short periods of time as is the case in pandemic outbreaks. Nanotechnology provides excellent platforms for formulating multivalent vaccines and pan-viral medicines for the treatment of COVID-19. Taken together, this review discusses the potential for the development of therapeutics by using the tools of biocomputing, nanotechnology, and phytopharming for accelerated therapeutic development to achieve effective COVID-19 treatment and associated complications, including new and emerging variants of SARS-COV-2 and other viral pandemics that may emerge or re-emerge.

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Screening of Natural Products Inhibitors of SARS-CoV-2 Entry

Cited by 26 publications

References 40 publications

Phytochemical Discrimination, Biological Activity and Molecular Docking of Water-Soluble Inhibitors from Saussurea costus Herb against Main Protease of SARS-CoV-2

Phytochemical Discrimination, Biological Activity and Molecular Docking of Water-Soluble Inhibitors from Saussurea costus Herb against Main Protease of SARS-CoV-2

Quinolizidines as Novel SARS-CoV-2 Entry Inhibitors

The challenges and opportunities for the development of COVID-19 therapeutics and preparing for the next pandemic

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