Natural and Nature-Derived Products Targeting Human Coronaviruses

Vougogiannopoulou, Konstantina; Corona, Angela; Tramontano, Enzo; Alexis, Μichael N.; Skaltsounis, Alexios‐Léandros

doi:10.3390/molecules26020448

Cited by 27 publications

(14 citation statements)

References 199 publications

(249 reference statements)

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“…However, and despite the huge number of research studies reported so far, the development of safe and effective drugs able to block the viral infection is still lacking and represents a major goal for the scientific world. Among all the possible chemical compounds, particular attention has been dedicated to molecules of natural origin [5][6][7][8], including extracts, single bioactive molecules, or entire classes of phytochemicals targeting SARS-CoV-2, and several of them are currently under investigation.…”

Section: Introductionmentioning

confidence: 99%

Rutin Is a Low Micromolar Inhibitor of SARS-CoV-2 Main Protease 3CLpro: Implications for Drug Design of Quercetin Analogs

et al. 2021

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The pandemic, due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has stimulated the search for antivirals to tackle COVID-19 infection. Molecules with known pharmacokinetics and already approved for human use have been demonstrated or predicted to be suitable to be used either directly or as a base for a scaffold-based drug design. Among these substances, quercetin is known to be a potent in vitro inhibitor of 3CLpro, the SARS-CoV-2 main protease. However, its low in vivo bioavailability calls for modifications to its molecular structure. In this work, this issue is addressed by using rutin, a natural flavonoid that is the most common glycosylated conjugate of quercetin, as a model. Combining experimental (spectroscopy and calorimetry) and simulation techniques (docking and molecular dynamics simulations), we demonstrate that the sugar adduct does not hamper rutin binding to 3CLpro, and the conjugated compound preserves a high potency (inhibition constant in the low micromolar range, Ki = 11 μM). Although showing a disruption of the pseudo-symmetry in the chemical structure, a larger steric volume and molecular weight, and a higher solubility compared to quercetin, rutin is able to associate in the active site of 3CLpro, interacting with the catalytic dyad (His41/Cys145). The overall results have implications in the drug-design of quercetin analogs, and possibly other antivirals, to target the catalytic site of the SARS-CoV-2 3CLpro.

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Section: Introductionmentioning

confidence: 99%

Rutin Is a Low Micromolar Inhibitor of SARS-CoV-2 Main Protease 3CLpro: Implications for Drug Design of Quercetin Analogs

et al. 2021

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“…A comprehensive review by Banerjee et al and Vougogiannopoulou explored the recent developments in the search for small-molecule inhibitors, including natural products targeting the SARS-CoV-2 M pro . Alliin, oleanic acid, kaempferol, quercetin, luteolin-7-glucoside, naringenin, and oleuropein are reported among natural products promising inhibitors of SARS-CoV-2 M pro (Banerjee et al, 2021; Vougogiannopoulou et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

Docking-based virtual screening and identification of potential COVID-19 main protease inhibitors from brown algae

Rashid

Khalil

Khan

et al. 2021

South African Journal of Botany

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COVID-19 (SARS-CoV-2) is a viral disease that causes acute respiratory syndrome, which has increased the morbidity and mortality rate throughout the world. World Health Organization has declared this COVID-19 outbreak as pandemic and classified health emergency throughout the world. In the recent past, outbreaks of SARS and MERS have shown the interspecies transmission potential of coronaviruses and limitations of already prescribed drugs to overcome this global public health issue. Therefore, there is a dire need to identify a new regimen of targeted drugs from natural compounds having anti-COVID19 potential. This study aimed at screening 1018 brown algal natural compounds (many of them previously reported to have immunomodulatory effects) having probable anti-COVID19 potentials. The source compounds were extracted from MarinLit, a database dedicated to marine natural products and screened against COVID-19 main protease. The top seven compounds were further analysed, and their interactions with the active site were visualized. This study will further warrant screening the potent compounds against the virus in in-vitro conditions.

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“…In addition to single molecules, some plant extracts also inhibited the SARS-CoV 3CL Pro activity in vitro [15,16]. Some natural compounds with potential against SARS-CoV-2 have been identified based on the work with SARS-CoV and related viruses and through in silico molecular docking studies [17][18][19][20][21]. The recent work of Zhou and Huang [22] reviews the current findings regarding natural compounds that might be considered for their potential antiviral activity against SARS-CoV-2, mostly based on previous experience with other coronaviruses.…”

Section: Introductionmentioning

confidence: 99%

Potential In Vitro Inhibition of Selected Plant Extracts against SARS-CoV-2 Chymotripsin-Like Protease (3CLPro) Activity

Guijarro-Real

Plazas

Rodríguez‐Burruezo

et al. 2021

Foods

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Antiviral treatments inhibiting Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication may represent a strategy complementary to vaccination to fight the ongoing Coronavirus disease 19 (COVID-19) pandemic. Molecules or extracts inhibiting the SARS-CoV-2 chymotripsin-like protease (3CLPro) could contribute to reducing or suppressing SARS-CoV-2 replication. Using a targeted approach, we identified 17 plant products that are included in current and traditional cuisines as promising inhibitors of SARS-CoV-2 3CLPro activity. Methanolic extracts were evaluated in vitro for inhibition of SARS-CoV-2 3CLPro activity using a quenched fluorescence resonance energy transfer (FRET) assay. Extracts from turmeric (Curcuma longa) rhizomes, mustard (Brassica nigra) seeds, and wall rocket (Diplotaxis erucoides subsp. erucoides) at 500 µg mL−1 displayed significant inhibition of the 3CLPro activity, resulting in residual protease activities of 0.0%, 9.4%, and 14.9%, respectively. Using different extract concentrations, an IC50 value of 15.74 µg mL−1 was calculated for turmeric extract. Commercial curcumin inhibited the 3CLPro activity, but did not fully account for the inhibitory effect of turmeric rhizomes extracts, suggesting that other components of the turmeric extract must also play a main role in inhibiting the 3CLPro activity. Sinigrin, a major glucosinolate present in mustard seeds and wall rocket, did not have relevant 3CLPro inhibitory activity; however, its hydrolysis product allyl isothiocyanate had an IC50 value of 41.43 µg mL−1. The current study identifies plant extracts and molecules that can be of interest in the search for treatments against COVID-19, acting as a basis for future chemical, in vivo, and clinical trials.

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Natural and Nature-Derived Products Targeting Human Coronaviruses

Cited by 27 publications

References 199 publications

Rutin Is a Low Micromolar Inhibitor of SARS-CoV-2 Main Protease 3CLpro: Implications for Drug Design of Quercetin Analogs

Rutin Is a Low Micromolar Inhibitor of SARS-CoV-2 Main Protease 3CLpro: Implications for Drug Design of Quercetin Analogs

Docking-based virtual screening and identification of potential COVID-19 main protease inhibitors from brown algae

Potential In Vitro Inhibition of Selected Plant Extracts against SARS-CoV-2 Chymotripsin-Like Protease (3CLPro) Activity

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