Phytochemicals: recent trends and future prospective in COVID-19

Coronavirus (COVID-19) is now growing aggressively over the globe and is exceedingly tricky to control due to the lack of available treatments or vaccines. Multiple investigations are now underway with the aim of identifying suitable herbal remedies and phytochemicals to reduce the incidence of COVID-19. In conclusion, certain herbal medications and phytopharmaceuticals could be a potential treatment strategy for mitigating SARS-CoV-2 hazards. Extensive research has been performed in pursuit of fresh options, including the use of phytochemical substances, which, in agreement with previous research, are not only promising against SARS-CoV-2, but also as coadjuvants in other diseases like diabetes. In addition, plants have been used for eras to cure a variety of infections, and exploration with plant-based natural products has been emphasized by the low toxicity of their metabolites and minimal side effects. In this chapter, we draw attention to various plant species and phytochemicals, a few of them belonging to the structural classes like phenolic, alkaloids, and terpenes with significant antiviral efficacy against SARS-CoV-2 that could be investigated as prospective medicines for the treatment of COVID-19. © 2023 Elsevier Inc. All rights reserved.

Seaweeds and Corals from the Brazilian Coast: Review on Biotechnological Potential and Environmental Aspects.

Brazil has a megadiversity that includes marine species that are distributed along 800 km of shoreline. This biodiversity status holds promising biotechnological potential. Marine organisms are important sources of novel chemical species, with applications in the pharmaceutical, cosmetic, chemical, and nutraceutical fields. However, ecological pressures derived from anthropogenic actions, including the bioaccumulation of potentially toxic elements and microplastics, impact promising species. This review describes the current status of the biotechnological and environmental aspects of seaweeds and corals from the Brazilian coast, including publications from the last 5 years (from January 2018 to December 2022). The search was conducted in the main public databases (PubChem, PubMed, Science Direct, and Google Scholar) and in the Espacenet database (European Patent Office-EPO) and the Brazilian National Property Institute (INPI). Bioprospecting studies were reported for seventy-one seaweed species and fifteen corals, but few targeted the isolation of compounds. The antioxidant potential was the most investigated biological activity. Despite being potential sources of macro- and microelements, there is a literature gap regarding the presence of potentially toxic elements and other emergent contaminants, such as microplastics, in seaweeds and corals from the Brazilian coast.

Effect of Exogenous Application of Tryptophan and Methyl Jasmonate on Some Metabolites and Antioxidant Activities of Feverfew

Tanacetum parthenium (L.) Schultz-Bip (feverfew) is among the important medicinal and aromatic plants due to its tryptophan (TRP), serotonin (SER), melatonin (MEL), and parthenolide (PRT) content. In recent studies, have reported TRP, MEL, and (PRT) are effective in the treatment of COVID-19, thus increasing the popularity of feverfew, which is rich in these valuable molecules. This study investigated the possible effects of exogenous foliar applications of methyl jasmonate (MeJA 0.5 mM) and TRP (20 mM) on plant TRP, SER, MEL, and PRT levels. During the pre-flowering period, endogenous TRP was measured as 128.9 mu g/mL and endogenous PRT as 1.53% mg/g in the leaves of the control group. During the flowering period, the MEL level was measured as 1.38 mu g/mL in the leaves of the TRP application group. In addition, in the pre-flowering period, MeJA-induced increases of 94.51% were determined in DPPH antioxidant activity and the total flavonoid content was 38.76 mg QE/g, whereas the highest total phenolic content of 51.63 mg GAE/g was found in flower samples of the control group. However, neither the developmental periods nor the treatments significantly affected the total phenolic content in the leaves.

Beauty, diversity, and potential uses of certain macrofungi

Macrofungi are diverse in their uses as good source of protein in our diet, nutraceuticals, cosmeceuticals medicine, and for making beautiful art pieces. Several species serve as decomposers and many form mycorrhizal associations with plants. The commercial cultivation of several macrofungi has been steadily increasing globally. Cultivation of Cordyceps militaris can be done in a variety of media including silkworm pupae, rice, or liquid nutrition. Macrofungi are diverse with complex and highly varied growth conditions and bioactive constituents, most macro-fungal resources have not yet been fully explored and implicated, leading to an urgent need for appropriate strategies to address the problem. Increasing attention has been paid to the cultivation and application, of these fungi as potential probiotics. The accumulated secondary metabolites in medicinal mushrooms have been widely accepted as sources of safe and effective nutraceuticals, cosmeceuticals, and pharmaceuticals. Various mushrooms are utilized as foods appreciated for their exquisite flavour and are used extensively for their medicinal properties. Recently, we saw how an invisibly small entity an ultramicroscopic virus created a turmoil in dynamic ecosystem of the planet Earth and caused the human societies to grind to a halt. Of course, human lives have pivoted around the metabolic ingenuity of fungi for a long time and these organisms can still be the tools to learn the intricacies of life, their mutualistic behaviour with other organisms and potential to produce a large number of secondary metabolites useful to fight diseases and providing good memory and better health are our present day concerns. Entangled body of tubes can teach the lessons of human survival in this crucial time of Corona pandemic. These macrofungi could modulate immune cell's response and possess antimicrobial, antioxidants, and anticancer properties. In Western Ghats as well as Himalayan mountain ranges of India, the lush green vegetation supports a variety of naturally occurring macrofungi. Brief details of some of the well-known fungi found in India, Macedonia, and other parts of the world are highlighted in this chapter. © The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022.

Exploring the Multitarget Potential of Iridoids: Advances and Applications.

Iridoids are secondary plant metabolites that are multitarget compounds active against various diseases. Iridoids are structurally classified into iridoid glycosides and non-glycosidic iridoids according to the presence or absence of intramolecular glycosidic bonds; additionally, iridoid glycosides can be further subdivided into carbocyclic iridoids and secoiridoids. These monoterpenoids belong to the cyclopentan[c]-pyran system, which has a wide range of biological activities, including antiviral, anticancer, antiplasmodial, neuroprotective, anti-thrombolytic, antitrypanosomal, antidiabetic, hepatoprotective, anti-oxidant, antihyperlipidemic and anti-inflammatory properties. The basic chemical structure of iridoids in plants (the iridoid ring scaffold) is biosynthesized in plants by the enzyme iridoid synthase using 8-oxogeranial as a substrate. With advances in phytochemical research, many iridoid compounds with novel structure and outstanding activity have been identified in recent years. Biologically active iridoid derivatives have been found in a variety of plant families, including Plantaginaceae, Rubiaceae, Verbenaceae, and Scrophulariaceae. Iridoids have the potential of modulating many biological events in various diseases. This review highlights the multitarget potential of iridoids and includes a compilation of recent publications on the pharmacology of iridoids. Several in vitro and in vivo models used, along with the results, are also included in the paper. This paper's systematic summary was created by searching for relevant iridoid material on websites such as Google Scholar, PubMed, SciFinder Scholar, Science Direct, and others. The compilation will provide the researchers with a thorough understanding of iridoid and its congeners, which will further help in designing a large number of potential compounds with a strong impact on curing various diseases.

Metabolic Profiling of Mimusops elengi Linn. Leaves extract and in silico anti-inflammatory assessment targeting NLRP3 inflammasome

Mimusops elengi Linn. Secondary metabolites of flavonoids, phenolic acids, coumarin classes and stilbene were identified by UPLC/ESI-QTOF-HRMS/MS technique with negative ion detection. Major Mimusops elengi flavonoids included Myricitrin, Myricetin, and Kaempferol-3-O-alpha-L-rhamnoside. The most abundant Coumarin and phenolic acids detected in the chromatogram included aesculin and quinic acid respectively. Down regulation of NLRP3 inflammasome activation inhibits the severe inflammatory responses caused by virus infection. Studying in silicobinding affinity of flavonoids, coumarins and phenolic acid in M. elengi leaves extract against the ADP binding site of NLRP3 protein (PDB code: 6NPY) demonstrated that investigated compounds have docking scores ranged from −6.20 to −12.30 kcal/mol. The best score was achieved by kaempferol-3-O-(6-p-coumaroyl) -glucoside(Compound 9) followed by aesculin (Compound 25) while Quinic acid (Compound 20) showed the lowest affinity toward ADP-binding site of NLRP3. © 2023 The Authors

Food Plant Secondary Metabolites Antiviral Activity and Their Possible Roles in SARS-CoV-2 Treatment: An Overview.

Natural products and plant extracts exhibit many biological activities, including that related to the defense mechanisms against parasites. Many studies have investigated the biological functions of secondary metabolites and reported evidence of antiviral activities. The pandemic emergencies have further increased the interest in finding antiviral agents, and efforts are oriented to investigate possible activities of secondary plant metabolites against human viruses and their potential application in treating or preventing SARS-CoV-2 infection. In this review, we performed a comprehensive analysis of studies through in silico and in vitro investigations, also including in vivo applications and clinical trials, to evaluate the state of knowledge on the antiviral activities of secondary metabolites against human viruses and their potential application in treating or preventing SARS-CoV-2 infection, with a particular focus on natural compounds present in food plants. Although some of the food plant secondary metabolites seem to be useful in the prevention and as a possible therapeutic management against SARS-CoV-2, up to now, no molecules can be used as a potential treatment for COVID-19; however, more research is needed.

GlPS1 overexpression accumulates coumarin secondary metabolites in transgenic Arabidopsis.

The dried root of Glehnia littoralis is a traditional Chinese herbal medicine mainly used to treat lung diseases and plays an important role in fighting coronavirus disease 2019 pneumonia in China. This study focused on the key enzyme gene GlPS1 for furanocoumarin synthesis in G. littoralis. In the 35S:GlPS1 transgenic Arabidopsis study, the Arabidopsis thaliana-overexpressing GlPS1 gene was more salt-tolerant than Arabidopsis in the blank group. Metabolomics analysis showed 30 differential metabolites in Arabidopsis, which overexpressed the GlPS1 gene. Twelve coumarin compounds were significantly upregulated, and six of these coumarin compounds were not detected in the blank group. Among these differential coumarin metabolites, isopimpinellin and aesculetin have been annotated by the Kyoto Encyclopedia of Genes and Genomes and isopimpinellin was not detected in the blank group. Through structural comparison, imperatorin was formed by dehydration and condensation of zanthotoxol and a molecule of isoprenol, and the difference between them was only one isoprene. Results showed that the GlPS1 gene positively regulated the synthesis of coumarin metabolites in A. thaliana and at the same time improved the salt tolerance of A. thaliana. Supplementary Information: The online version contains supplementary material available at 10.1007/s11240-022-02427-w.

Plants as Biofactories for Therapeutic Proteins and Antiviral Compounds to Combat COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a profound impact on the world's health and economy. Although the end of the pandemic may come in 2023, it is generally believed that the virus will not be completely eradicated. Most likely, the disease will become an endemicity. The rapid development of vaccines of different types (mRNA, subunit protein, inactivated virus, etc.) and some other antiviral drugs (Remdesivir, Olumiant, Paxlovid, etc.) has provided effectiveness in reducing COVID-19's impact worldwide. However, the circulating SARS-CoV-2 virus has been constantly mutating with the emergence of multiple variants, which makes control of COVID-19 difficult. There is still a pressing need for developing more effective antiviral drugs to fight against the disease. Plants have provided a promising production platform for both bioactive chemical compounds (small molecules) and recombinant therapeutics (big molecules). Plants naturally produce a diverse range of bioactive compounds as secondary metabolites, such as alkaloids, terpenoids/terpenes and polyphenols, which are a rich source of countless antiviral compounds. Plants can also be genetically engineered to produce valuable recombinant therapeutics. This molecular farming in plants has an unprecedented opportunity for developing vaccines, antibodies, and other biologics for pandemic diseases because of its potential advantages, such as low cost, safety, and high production volume. This review summarizes the latest advancements in plant-derived drugs used to combat COVID-19 and discusses the prospects and challenges of the plant-based production platform for antiviral agents.

Computer-Aided Drug Discovery Approaches in the Identification of Natural Products against SARS-CoV-2: A Review.

BACKGROUND: The COVID-19 pandemic is raising a worldwide search for compounds that could act against the disease, mainly due to its mortality. With this objective, many researchers invested in the discovery and development of drugs of natural origin. To assist in this search, the potential of computational tools to reduce the time and cost of the entire process is known. OBJECTIVE: Thus, this review aimed to identify how these tools have helped in the identification of natural products against SARS-CoV-2. METHODS AND RESULTS: For this purpose, a literature review was carried out with scientific articles with this proposal where it was possible to observe that different classes of primary and, mainly, secondary metabolites were evaluated against different molecular targets, mostly being enzymes and spike, using computational techniques, with emphasis on the use of molecular docking. CONCLUSION: However, it is noted that in silico evaluations still have much to contribute to the identification of an anti-SARS-CoV-2 substance, due to the vast chemical diversity of natural products, identification and use of different molecular targets and computational advancement.

Gas chromatography-mass spectrometry (GC-MS) profiling of aqueous methanol fraction of Plagiochasma appendiculatum Lehm. & Lindenb. and Sphagnum fimbriatum Wilson for probable antiviral potential.

The bryophytes consist of liverworts, mosses, and hornworts, among which the liverworts are quite different in having cellular oil bodies and contain numerous terpenoids, acetogenins, quinones, phenylpropanoids, flavonoids, etc. These metabolites exhibit interesting biological activity such as allergenic response, insecticide, cytotoxic, neurotrophic, antimicrobial, and anti-HIV actions, etc. Though several bioactive compounds have been isolated in many liverworts, yet most of the liverworts have been unexplored till date regarding their phytochemistry. The ability of liverworts to generate a wide range of important phytochemicals makes them a hoard of bioactive compounds. In the past, a few species of bryophytes have been evaluated against a few viruses and interesting results were obtained that showed their role as an immunity enhancer against viral infection. The phytoconstituents found in liverworts and mosses can be useful to increase human immunity against a variety of viruses, including SARS-CoV-2. Keeping this in view, one of the most developed and robust metabolomics technologies, Gas chromatography-mass spectroscopy (GC-MS) was used to estimate the various phytoconstituents found in a commonly growing thalloid liverwort, Plagiochasma appendiculatum, and moss Sphagnum fimbriatum. The obtained profiles were appraised for their bioactive potential and probable role as antiviral agents.

Natural Products as Potential Therapeutic Agents for SARS-CoV-2: A Medicinal Chemistry Perspective.

Coronavirus is a single-stranded RNA virus discovered by virologist David Tyrrell in 1960. Till now seven human corona viruses have been identified including HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, SARS-CoV, MERS-CoV and SARS-CoV-2. In the present scenario, the SARS-CoV-2 outbreak causing SARS-CoV-2 pandemic, became the most serious public health emergency of the century worldwide. Natural products have long history and advantages for the drug discovery process. Almost 80% of drugs present in market are evolved from the natural resources. With the outbreak of SARS-CoV-2 pandemic, natural product chemists have made significant efforts for the identification of natural molecules which can be effective against the SARS-CoV-2. In current compilation we have discussed in vitro and in vivo anti-viral potential of natural product-based leads for the treatment of SARS-CoV-2. We have classified these leads in different classes of natural products such as alkaloids, terpenoids, flavonoids, polyphenols, quinones, cannabinoids, steroids, glucosinolates, diarylheptanoids, etc. and discussed the efficacy and mode of action of these natural molecules. The present review will surely opens new direction in future for the development of promising drug candidates particularly from the natural origin against coronaviruses and other viral diseases.

Effectiveness of the Fungal Metabolite 3-O-Methylfunicone towards Canine Coronavirus in a Canine Fibrosarcoma Cell Line (A72).

Canine coronavirus (CCoV), an alphacoronavirus, may cause self-limiting enteric disease in dogs, especially in puppies. The noteworthy plasticity of coronaviruses (CoVs) occurs through mutation and recombination processes, which sometimes generate new dangerous variants. The ongoing SARS-CoV-2 pandemic and the isolation of a novel canine-feline recombinant alphacoronavirus from humans emphasizes the cross-species transmission ability of CoVs. In this context, exploring antiviral compounds is essential to find new tools for fighting against CoVs infections. Fungi produce secondary metabolites, which are often developed as antibiotics, fungicides, hormones, and plant growth regulators. Previous examinations of benzo-γ-pyrone 3-O-methylfunicone (OMF), obtained from Talaromyces pinophilus, showed that it reduces the infectivity of hepatitis C virus and bovine herpesvirus 1. Based on this evidence, this study evaluated the antiviral ability of OMF against CCoV infection in a canine fibrosarcoma (A72) cell line. During CCoV infection, a non-toxic dose of OMF markedly increased features of cell viability. Moreover, OMF induced a significant reduction in virus yield in the presence of an intense downregulation of the viral nucleocapsid protein (NP). These findings occurred in the presence of a marked reduction in the aryl hydrocarbon receptor (AhR) expression. Taken together, preliminary findings suggest that OMF inhibiting AhR shows promising activity against CCoV infection.

Phycochemistry and bioactivity of cyanobacterial secondary metabolites.

Microbes are a huge contributor to people's health around the world since they produce a lot of beneficial secondary metabolites. Cyanobacteria are photosynthetic prokaryotic bacteria cosmopolitan in nature. Adaptability of cyanobacteria to wide spectrum of environment can be contributed to the production of various secondary metabolites which are also therapeutic in nature. As a result, they are a good option for the development of medicinal molecules. These metabolites could be interesting COVID-19 therapeutic options because the majority of these compounds have demonstrated substantial pharmacological actions, such as neurotoxicity, cytotoxicity, and antiviral activity against HCMV, HSV-1, HHV-6, and HIV-1. They have been reported to produce a single metabolite active against wide spectrum of microbes like Fischerella ambigua produces ambigols active against bacteria, fungi and protozoa. Similarly, Moorea producens produces malygomides O and P, majusculamide C and somocystinamide which are active against bacteria, fungi and tumour cells, respectively. In addition to the above, Moorea sp. produce apratoxin A and dolastatin 15 possessing anti cancerous activity but unfortunately till date only brentuximab vedotin (trade name Adcetris), a medication derived from marine peptides, for the treatment of Hodgkin lymphoma and anaplastic large cell lymphoma has been approved by FDA. However, several publications have effectively described and categorised cyanobacterial medicines based on their biological action. In present review, an effort is made to categorize cyanobacterial metabolites on the basis of their phycochemistry. The goal of this review is to categorise cyanobacterial metabolites based on their chemical functional group, which has yet to be described.

GC-MS profiling of Bauhinia variegata major phytoconstituents with computational identification of potential lead inhibitors of SARS-CoV-2 Mpro.

Severe acute respiratory syndrome coronavirus 2 was originally identified in Wuhan city of China in December 2019 and it spread rapidly throughout the globe, causing a threat to human life. Since targeted therapies are deficient, scientists all over the world have an opportunity to develop novel drug therapies to combat COVID-19. After the declaration of a global medical emergency, it was established that the Food and Drug Administration (FDA) could permit the use of emergency testing, treatments, and vaccines to decrease suffering, and loss of life, and restore the nation's health and security. The FDA has approved the use of remdesivir and its analogs as an antiviral medication, to treat COVID-19. The primary protease of SARS-CoV-2, which has the potential to regulate coronavirus proliferation, has been a viable target for the discovery of medicines against SARS-CoV-2. The present research deals with the in silico technique to screen phytocompounds from a traditional medicinal plant, Bauhinia variegata for potential inhibitors of the SARS-CoV-2 main protease. Dried leaves of the plant B. variegata were used to prepare aqueous and methanol extract and the constituents were analyzed using the GC-MS technique. A total of 57 compounds were retrieved from the aqueous and methanol extract analysis. Among these, three lead compounds (2,5 dimethyl 1-H Pyrrole, 2,3 diphenyl cyclopropyl methyl phenyl sulphoxide, and Benzonitrile m phenethyl) were shown to have the highest binding affinity (-5.719 to -5.580 kcal/mol) towards SARS-CoV-2 Mpro. The post MD simulation results also revealed the favorable confirmation and stability of the selected lead compounds with Mpro as per trajectory analysis. The Prime MM/GBSA binding free energy supports this finding, the top lead compound 2,3 diphenyl cyclopropyl methyl phenyl sulphoxide showed high binding free energy (-64.377 ± 5.24 kcal/mol) towards Mpro which reflects the binding stability of the molecule with Mpro. The binding free energy of the complexes was strongly influenced by His, Gln, and Glu residues. All of the molecules chosen are found to have strong pharmacokinetic characteristics and show drug-likeness properties. The lead compounds present acute toxicity (LD50) values ranging from 670 mg/kg to 2500 mg/kg; with toxicity classifications of 4 and 5 classes. Thus, these compounds could behave as probable lead candidates for treatment against SARS-CoV-2. However further in vitro and in vivo studies are required for the development of medication against SARS-CoV-2.

Neuroprotective Drug Discovery From Phytochemicals and Metabolites for CNS Viral Infection: A Systems Biology Approach With Clinical and Imaging Validation.

Background: Recent studies have reported that pulmo-neurotropic viruses can cause systemic invasion leading to acute respiratory failure and neuroinfection. The tetracycline class of secondary metabolites of microorganisms is effective against several migrating neurotropic viral disorders, as Japanese-Encephalitis (JE), Severe-Acute-Respiratory-Syndrome Coronavirus-2 (SARS-COV2), Human-Immunodeficiency-Virus (HIV), and Simian-Immunodeficiency-Virus (SIV). Another microbial secondary metabolite, cephalosporin, can be used for anti-viral combination therapy. However, a substantial public health debacle is viral resistance to such antibiotics, and, thus, one needs to explore the antiviral efficiency of other secondary metabolites, as phytochemicals. Hence, here, we investigate phytochemicals like podophyllotoxin, chlorogenic acid, naringenin, and quercetin for therapeutic efficiency in neurotropic viral infections. Methods: To investigate the possibility of the afferent neural pathway of migrating virus in man, MRI scanning was performed on human subjects, whereby the connections between cranial nerves and the brain-stem/limbic-region were assessed by fiber-tractography. Moreover, human clinical-trial assessment (n = 140, p = 0.028) was done for formulating a quantitative model of antiviral pharmacological intervention. Furthermore, docking studies were performed to identify the binding affinity of phytochemicals toward antiviral targets as (i) host receptor [Angiotensin-converting Enzyme-2], (ii) main protease of SARS-COV2 virus (iii) NS3-Helicase/Nucleoside triphosphatase of Japanese-encephalitis-virus, and the affinities were compared to standard tetracycline and cephalosporin antibiotics. Then, network pharmacology analysis was utilized to identify the possible mechanism of action of those phytochemicals. Results: Human MRI-tractography analysis showed fiber connectivity, as: (a) Path-1: From the olfactory nerve to the limbic region (2) Path-2: From the peripheral glossopharyngeal nerve and vagus nerves to the midbrain-respiratory-center. Docking studies revealed comparable binding affinity of phytochemicals, tetracycline, and cephalosporin antibiotics toward both (a) virus receptors, (b) host cell receptors where virus-receptor binds. The phytochemicals effectively countered the cytokine storm-induced neuroinflammation, a critical pathogenic pathway. We also found that a systems-biology-based double-hit mathematical bi-exponential model accounts for patient survival-curve under antiviral treatment, thus furnishing a quantitative-clinical framework of secondary metabolite action on virus and host cells. Conclusion: Due to the current viral resistance to antibiotics, we identified novel phytochemicals that can have clinical therapeutic application to neurotropic virus infection. Based on human MRI scanning and clinical-trial analysis, we demarcated the anatomical pathway and systems-biology-based quantitative formulation of the mechanism of antiviral action.

An Update on Promising Agents against COVID-19: Secondary Metabolites and Mechanistic Aspects.

BACKGROUND: Coronavirus disease 2019 (COVID­19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and is associated with a high level of mortality. OBJECTIVE: This updated review aims to present the most important traditional medicinal plants and some of their secondary metabolites that have previously and more recently been shown to affect viruses and may represent a beneficial contributory step against SARS-CoV-2 as the cause of COVID-19. Moreover, the mechanism aspects of these secondary metabolites were discussed, which may help find more reliable drugs against SARSCoV- 2. METHODS: Articles were searched on scientific websites including Google Scholar, Scopus, Web of Science, PubMed, and IranMedex using the search terms herbal medicine and traditional medicine with coronavirus, SARS-CoV-2, or COVID-19. Human, animal, and in vitro studies were identified in the search. RESULTS: Medicinal plants and their secondary metabolites may possess a potential role in combating this disease, and researchers suggest that some of these plants and their constituent compounds have inhibitory activity on coronaviruses. Numerous medicinal plants, their extracts, and secondary metabolites have been investigated over a period of time for antiviral activity. Among them, kaempferol, silybin, myricitrin, licoleafol, and curcumin are promising agents with potential activity against SARS-CoV-2. Natural compounds can form strong bonds with the active sites of SARS-CoV-2 protease. Structural and non-structural SARS-CoV-2 proteins such as Spike protein, PLpro, and 3CLpro are inhibited by these phytochemicals. CONCLUSION: Prospective treatments targeted at the life cycle stages of the virus may eventuate from research endeavors, and it must not be discounted that therapy originally derived from plant secondary metabolite sources may potentially have a part to play.

Hormonal regulation of health-promoting compounds in tea (Camellia sinensis L.).

Tea is the most frequently consumed natural beverage across the world produced with the young leaves and shoots of the evergreen perennial plant Camellia sinensis (L.) O. Kuntze. The expanding global appeal of tea is partly attributed to its health-promoting benefits such as anti-inflammation, anti-cancer, anti-allergy, anti-hypertension, anti-obesity, and anti- SARS-CoV-2 activity. The many advantages of healthy tea intake are linked to its bioactive substances such as tea polyphenols, flavonoids (catechins), amino acids (theanine), alkaloids (caffeine), anthocyanins, proanthocyanidins, etc. that are produced through secondary metabolic pathways. Phytohormones regulate secondary metabolite biosynthesis in a variety of plants, including tea. There is a strong hormonal response in the biosynthesis of polyphenols, catechins, theanine and caffeine in tea under control and perturbed environmental conditions. In addition to the impact of preharvest plant hormone manipulation on green tea quality, changes in hormones of postharvest tea also regulate quality-related metabolites in tea. In this review, we discuss the health benefits of major tea constituents and the role of various plant hormones in improving the endogenous levels of these compounds for human health benefits. The fact that the ratio of tea polyphenols to amino acids and the concentrations of tea components are changed by environmental conditions, most notably by climate change-associated variables, the selection and usage of optimal hormone combinations may aid in sustaining tea quality, and thus can be beneficial to both consumers and producers.

Protocetraric and Salazinic Acids as Potential Inhibitors of SARS-CoV-2 3CL Protease: Biochemical, Cytotoxic, and Computational Characterization of Depsidones as Slow-Binding Inactivators.

The study investigated the inhibitory activity of protocetraric and salazinic acids against SARS-CoV-2 3CLpro. The kinetic parameters were determined by microtiter plate-reading fluorimeter using a fluorogenic substrate. The cytotoxic activity was tested on murine Sertoli TM4 cells. In silico analysis was performed to ascertain the nature of the binding with the 3CLpro. The compounds are slow-binding inactivators of 3CLpro with a Ki of 3.95 µM and 3.77 µM for protocetraric and salazinic acid, respectively, and inhibitory efficiency kinact/Ki at about 3 × 10-5 s-1µM-1. The mechanism of inhibition shows that both compounds act as competitive inhibitors with the formation of a stable covalent adduct. The viability assay on epithelial cells revealed that none of them shows cytotoxicity up to 80 µM, which is well below the Ki values. By molecular modelling, we predicted that the catalytic Cys145 makes a nucleophilic attack on the carbonyl carbon of the cyclic ester common to both inhibitors, forming a stably acyl-enzyme complex. The computational and kinetic analyses confirm the formation of a stable acyl-enzyme complex with 3CLpro. The results obtained enrich the knowledge of the already numerous biological activities exhibited by lichen secondary metabolites, paving the way for developing promising scaffolds for the design of cysteine enzyme inhibitors.

Simple Theoretical Criterion for Selection of Natural Compounds with Anti-COVID-19 Activity.

BACKGROUND: A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the leading threat to global health. An effective antiviral could not only help those still vulnerable to the virus but could be a critical treatment if a virus emerges toward evading coronavirus disease 2019 (COVID-19) vaccines. Despite the significant efforts to test already-approved drugs for their potential to kill the virus, researchers found very few actually worked. METHODS: The present report uses the electronic molecular descriptors, the quasi-valence number (AQVN), and the electron-ion interaction potential (EIIP), for the analysis of natural compounds with proven therapeutic activity against the COVID-19. RESULTS: Based on the analysis of the electronic properties of natural compounds which are effective against SARS-CoV-2 virus the simple theoretical criterion for the selection of candidate compounds for the treatment of COVID-19 is proposed. CONCLUSIONS: The proposed theoretical criterion can be used for the identification and optimization of new lead compounds for the treatment of the COVID-19 disease and for the selection of the food and food supplements which could have a beneficial effect on COVID-19 patients.