Naturally Occurring Xanthones; Biological Activities, Chemical Profiles and In Silico Drug Discovery

Xanthones are widely distributed polyphenols, present commonly in higher plants; Garcinia, Calophyllum, Hypericum, Platonia, Mangifera, Gentiana and Swertia. Xanthone tricyclic scaffold is able to interact with different biological targets, showing antibacterial and cytotoxic effects, as well as potent effects against osteoarthritis, malaria, and cardiovascular diseases. Thus, in this article we focused on pharmacological effects, applications and preclinical studies with the recent updates of xanthon´s isolated compounds from 2017-2020. We found that only α-mangostin, gambogic acid, and mangiferin, have been subjected to preclinical studies with particular emphasis on the development of anticancer, diabetes, antimicrobial and hepatoprotective therapeutics. Molecular docking calculations were performed to predict the binding affinities of xanthone-derived compounds against SARS-CoV-2 Mpro. According to the results, cratoxanthone E and morellic acid demonstrated promising binding affinities towards SARS-CoV-2 Mpro with docking scores of −11.2 and −11.0 kcal/mol, respectively. Binding features manifested the capability of cratoxanthone E and morellic acid to exhibit nine and five hydrogen bonds, respectively, with the key amino acids of the Mpro active site. In conclusion, cratoxanthone E and morellic acid are promising anti-COVID-19 drug candidates that warrant further detailed in vivo experimental estimation and clinical assessment.

In Silico Screening of Natural Products as Potential Inhibitors of SARS-CoV-2 Using Molecular Docking Simulation.

OBJECTIVE: To explore potential natural products against severe acute respiratory syndrome coronavirus (SARS-CoV-2) via the study of structural and non-structural proteins of human coronaviruses. METHODS: In this study, we performed an in-silico survey of 25 potential natural compounds acting against SARS-CoV-2. Molecular docking studies were carried out using compounds against 3-chymotrypsin-like protease (3CLPRO), papain-like protease (PLPRO), RNA-dependent RNA polymerase (RdRp), non-structural protein (nsp), human angiotensin converting enzyme 2 receptor (hACE2R), spike glycoprotein (S protein), abelson murine leukemia viral oncogene homolog 1 (ABL1), calcineurin-nuclear factor of activated T-cells (NFAT) and transmembrane protease serine 2. RESULTS: Among the screened compounds, amentoflavone showed the best binding affinity with the 3CLPRO, RdRp, nsp13, nsp15, hACE2R. ABL1 and calcineurin-NFAT; berbamine with hACE2R and ABL1; cepharanthine with nsp10, nsp14, nsp16, S protein and ABL1; glucogallin with nsp15; and papyriflavonol A with PLPRO protein. Other good interacting compounds were juglanin, betulinic acid, betulonic acid, broussooflavan A, tomentin A, B and E, 7-methoxycryptopleurine, aloe emodin, quercetin, tanshinone I, tylophorine and furruginol, which also showed excellent binding affinity towards a number of target proteins. Most of these compounds showed better binding affinities towards the target proteins than the standard drugs used in this study. CONCLUSION: Natural products or their derivatives may be one of the potential targets to fight against SARS-CoV-2.

Myricetin bioactive effects: moving from preclinical evidence to potential clinical applications.

Several flavonoids have been recognized as nutraceuticals, and myricetin is a good example. Myricetin is commonly found in plants and their antimicrobial and antioxidant activities is well demonstrated. One of its beneficial biological effects is the neuroprotective activity, showing preclinical activities on Alzheimer, Parkinson, and Huntington diseases, and even in amyotrophic lateral sclerosis. Also, myricetin has revealed other biological activities, among them as antidiabetic, anticancer, immunomodulatory, cardiovascular, analgesic and antihypertensive. However, few clinical trials have been performed using myricetin as nutraceutical. Thus, this review provides new insights on myricetin preclinical pharmacological activities, and role in selected clinical trials.

Aromatic Herbs, Medicinal Plant-Derived Essential Oils, and Phytochemical Extracts as Potential Therapies for Coronaviruses: Future Perspectives.

After its recent discovery in patients with serious pneumonia in Wuhan (China), the 2019 novel coronavirus (2019-nCoV), named also Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has spread quickly. Unfortunately, no drug or vaccine for treating human this coronavirus infection is available yet. Numerous options for controlling or preventing emerging 2019-nCoV infections may be predicted, including vaccines, interferon therapies, and small-molecule drugs. However, new interventions are likely to require months to years to develop. In addition, most of the existing antiviral treatments frequently lead to the development of viral resistance combined with the problem of side effects, viral re-emergence, and viral dormancy. The pharmaceutical industry is progressively targeting phytochemical extracts, medicinal plants, and aromatic herbs with the aim of identifying lead compounds, focusing principally on appropriate alternative antiviral drugs. Spices, herbal medicines, essential oils (EOs), and distilled natural products provide a rich source of compounds for the discovery and production of novel antiviral drugs. The determination of the antiviral mechanisms of these natural products has revealed how they interfere with the viral life cycle, i.e., during viral entry, replication, assembly, or discharge, as well as virus-specific host targets. Presently, there are no appropriate or approved drugs against CoVs, but some potential natural treatments and cures have been proposed. Given the perseverance of the 2019-nCoV outbreak, this review paper will illustrate several of the potent antiviral chemical constituents extracted from medicinal and aromatic plants, natural products, and herbal medicines with recognized in vitro and in vivo effects, along with their structure-effect relationships. As this review shows, numerous potentially valuable aromatic herbs and phytochemicals are awaiting assessment and exploitation for therapeutic use against genetically and functionally different virus families, including coronaviruses.