Virtual Screening of Citrus Flavonoid Tangeretin: A Promising Pharmacological Tool for the Treatment and Prevention of Zika fever and COVID-19

Rocha, Matheus Nunes da; Alves, Daniela Ribeiro; Marinho, Márcia Machado; Morais, Selene Maia de; Marinho, Emmanuel Silva

doi:10.1142/s2737416521500137

Cited by 18 publications

(11 citation statements)

References 68 publications

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“…Previous computational studies have revealed that taxifolin could be a potential inhibitor against the SARS-CoV-2 Mpro enzyme [33]. Moreover, tangeretin showed potential for the treatment and prevention of COVID-19 [34], while, hispidulin showed a better binding affinity to Mpro of SARS-CoV-2 and ACE2 receptor than hydroxychloroquine and could be used as a therapeutic candidate against COVID-19 [35]. No studies, either computational or in vitro, were reported for the compounds pectolinarigenin and gardenin B regarding their effects on SARS-CoV-2.…”

Section: Introductionmentioning

confidence: 99%

Naturally Available Flavonoid Aglycones as Potential Antiviral Drug Candidates against SARS-CoV-2

et al. 2021

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Flavonoids are important secondary plant metabolites that have been studied for a long time for their therapeutic potential in inflammatory diseases because of their cytokine-modulatory effects. Five flavonoid aglycones were isolated and identified from the hydrolyzed aqueous methanol extracts of Anastatica hierochuntica L., Citrus reticulata Blanco, and Kickxia aegyptiaca (L.) Nabelek. They were identified as taxifolin (1), pectolinarigenin (2), tangeretin (3), gardenin B (4), and hispidulin (5). These structures were elucidated based on chromatographic and spectral analysis. In this study, molecular docking studies were carried out for the isolated and identified compounds against SARS-CoV-2 main protease (Mpro) compared to the co-crystallized inhibitor of SARS-CoV-2 Mpro (α-ketoamide inhibitor (KI), IC50 = 66.72 µg/mL) as a reference standard. Moreover, in vitro screening against SARS-CoV-2 was evaluated. Compounds 2 and 3 showed the highest virus inhibition with IC50 12.4 and 2.5 µg/mL, respectively. Our findings recommend further advanced in vitro and in vivo studies of the examined isolated flavonoids, especially pectolinarigenin (2), tangeretin (3), and gardenin B (4), either alone or in combination with each other to identify a promising lead to target SARS-CoV-2 effectively. This is the first report of the activity of these compounds against SARS-CoV-2.

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Section: Introductionmentioning

confidence: 99%

Naturally Available Flavonoid Aglycones as Potential Antiviral Drug Candidates against SARS-CoV-2

et al. 2021

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“…Its hydrophobic core of M17 has a hydropathic index 1.9 demonstrating that this region attracts substances capable of crossing the PM. These compounds' cell invading ability further is explained by MLOGP evaluation (Table 1) (Alves et al, 2021;Moriguchi et al, 1992;Rocha et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…After that, the files were uploaded and submitted to the web-based tool, SwissDock (http://www.swissdock.ch/docking#) (Webb & Sali, 2019), Swiss Institute of Bioinformatic (SIB) server, for molecular docking simulation. Subsequently, the results received were processed in the UCSF Chimera® software, for analysis and comparison of the distances and interactions of curcumins with the interaction amino acid residues of N3, Azithromycin(AZT), and Baricitinib(BRT) (Alves et al, 2021;Rocha et al, 2021). From the distances obtained, the data were computed and plotted on the web-based tool, Morpheus (https://software.broadinstitute.org/morpheus/), and heatmaps were used to visualize changes in the ligand-residue interaction profiles (L-R's), being evaluated by the Pearson statistical test to detect similarity.…”

Section: Methodsmentioning

confidence: 99%

Curcumins and its derivatives as potential inhibitors of New Coronavirus (COVID-19) main protease: an in silico strategy

Alves

Rocha

Passos

et al. 2022

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Coronavirus (COVID-19) disease outbreak caused a worldwide pandemic with a powerful lethal potential and still, there is no specific treatment to it. Natural bioactive molecules like curcumins were investigated in this work aiming to block the active site of COVID-19 Main protease (Mpro), since they present several biological activities, being more suitable in terms of fewer side effects, once this disease overloads the immune system of patients. Hereby, curcumin and several derivatives were screened for their ability to react with Mpro receptors (PDB: 6LU7). N3, Azithromycin (AZT), and Baracitinib (BRT) were evaluated as positive controls and in combined therapeutics possibilities with curcumins. N3, AZT, and BRT bound to different protein receptors, and also it was observed that N3 bound in the same site as hexahydrocurcumin and curcumin glucuronide bound at the AZT’s site and bisdemethoxycurcumin, curcumin, curcumin sulfate, cyclocurcumin, demethoxycurcumin, dihydrocurcumin and hexahydrocurcuminol bound at BRT’s site. All molecules analyzed have high force interaction fields. Once the viral activity is mainly intracellular, these compounds also were evaluated for their hydropathic abilities. All molecules were classified and considered capable of membrane cell invading. These results suggest that the therapeutic approach of the curcumin derivatives associated with AZT and the antiviral inhibitor N3 is promissory for future evaluation of their synergism in in vitro and in vivo tests to define their additional viability in the treatment of COVID-19.

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“…They have shown various modes of action including targeting viral attachment, its entry and multiplication, and suppressing inflammation [30]. Tangeretin, a citrus polymethoxyflavone compound, which is generally found in citrus peel oil is found to be greatly effective in COVID-19 treatment [31]. Similarly, other important plants like the Curcumin longa, Oroxylum indicum, Echinacea purpurea, Cinchona sp., Glycyrrhiza glabra, Ocimum sanctum, Withania somnifera and many others have reported immensely in treating COVID-19 disease.…”

Section: Potential Targets Of Medicinal Plants In Covid-19 Pathogenesismentioning

confidence: 99%

“…The anti-inflammatory activity of medicinal plants can check the cytokine storm in the affected patients and inhibit viral entry and replication [30]. Tangeretin, a citrus polymethoxyflavone compound, which is generally found in citrus peel oil is found to be effective in COVID-19 treatment [31]. Cannabis sativa, which has been used for various medical purposes, has shown anti-inflammatory activity associated with COVID-19 infection [91].…”

Section: Inflammationmentioning

confidence: 99%

Jeopardy of COVID-19: Rechecking the Perks of Phytotherapeutic Interventions

et al. 2021

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The novel coronavirus disease (COVID-19), the reason for worldwide pandemic, has already masked around 220 countries globally. This disease is induced by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). Arising environmental stress, increase in the oxidative stress level, weak immunity and lack of nutrition deteriorates the clinical status of the infected patients. Though several researches are at its peak for understanding and bringing forward effective therapeutics, yet there is no promising solution treating this disease directly. Medicinal plants and their active metabolites have always been promising in treating many clinical complications since time immemorial. Mother nature provides vivid chemical structures, which act multi-dimensionally all alone or synergistically in mitigating several diseases. Their unique antioxidant and anti-inflammatory activity with least side effects have made them more effective candidate for pharmacological studies. These medicinal plants inhibit attachment, encapsulation and replication of COVID-19 viruses by targeting various signaling molecules such as angiotensin converting enzyme-2, transmembrane serine protease 2, spike glycoprotein, main protease etc. This property is re-examined and its potency is now used to improve the existing global health crisis. This review is an attempt to focus various antiviral activities of various noteworthy medicinal plants. Moreover, its implications as prophylactic or preventive in various secondary complications including neurological, cardiovascular, acute kidney disease, liver disease are also pinpointed in the present review. This knowledge will help emphasis on the therapeutic developments for this novel coronavirus where it can be used as alone or in combination with the repositioned drugs to combat COVID-19.

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Virtual Screening of Citrus Flavonoid Tangeretin: A Promising Pharmacological Tool for the Treatment and Prevention of Zika fever and COVID-19

Cited by 18 publications

References 68 publications

Naturally Available Flavonoid Aglycones as Potential Antiviral Drug Candidates against SARS-CoV-2

Naturally Available Flavonoid Aglycones as Potential Antiviral Drug Candidates against SARS-CoV-2

Curcumins and its derivatives as potential inhibitors of New Coronavirus (COVID-19) main protease: an in silico strategy

Jeopardy of COVID-19: Rechecking the Perks of Phytotherapeutic Interventions

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