Potential inhibition of Melaleuca leucadendron L. compounds against the NSP5 SARS CoV-2 protein

COVID-19 is an infectious disease caused by Severe Acute Respiratory Syndrome (SARS-CoV-2), causing a global health emergency as a pandemic disease. The lack of certain drug molecules or treatment strategies to fight this disease makes it worse. Therefore, effective drug molecules are needed to fight COVID-19. Non Structural Protein (NSP5) or called Main Protease (Mpro) of SARS CoV 2, a key component of this viral replication, is considered a key target for anti-COVID-19 drug development. The purpose of this study is to determine whether the compounds in the Melaleuca leucadendron L. plant such as 1,8-cineole, terpene, guaiol, linalol, a-selinenol, beta-eudesmol and P-eudesmol are predicted to have antiviral activity for COVID-19. Interaction of compounds with NSP5 with PDB code 6WNP analyzed using molecular docking with Molegro Virtual Docker. Based on binding affinity, the highest potential as an anti-viral is Terpineol with binding energy (-119.743 kcal/mol). The results of the interaction showed that terpinol has similarities in all three amino acid residues namely Cys 145, Gly 143, and Glu 166 with remdesivir and native ligand. Melaleuca leucadendron L. may represent a potential herbal treatment to act as: COVID-19 NSP5, however these findings must be validated in vitro and in vivo.

In silico evaluation of some commercially available terpenoids as spike glycoprotein of SARS-CoV-2 - inhibitors using molecular dynamic approach.

Coronavirus, an extremely contagious infections disease had a harmful effect on the world's population. It is a family of enveloped, single-stranded, positive-strand RNA viruses of Nidovirales order belongs to coroviridae family. At present, worldwide several lakhs of deaths and several billions of infections have been reported. Hence, the focus of the present study was to assess the SARS-CoV-2 enzyme inhibitory potential of certain commercially available terpenoids using Lamarckian genetic algorithm as a working principle and molecular dynamic studies was also performed. AutoDock 4.2 software was used to perform the computational docking calculations of terpenoids against SARS-CoV-2 enzyme. The terpenoids such as, Andrographolide, Betulonic acid, Erythrodiol, Friedelin, Mimuscopic acid, Moronic acid, and Retinol were selected based on the drug likeness properties. Remdesivir a well-known anti-viral drug was selected as the standard drug. Molecular dynamic simulation studies were carried using Desmond module of Schrodinger Suite. In the current study we observed that, Friedelin was exhibited excellent SARS-CoV-2 enzyme inhibitory potential than the standard drug and other selected terpenoids. Friedelin and the standard Remdesivir was undergone the molecular dynamic studies and Friedelin showed a good number of hydrogen bonds over the simulation time of 100 ns. Based on the in silico computational evaluation, it can be concluded that Friedelin could be worthwhile terpenoid against SARS-CoV-2 spike protein. A further study on Friedelin is required to develop a potential chemical entity against the management of COVID disease.Communicated by Ramaswamy H. Sarma.

In silico targeting of SARS-CoV-2 spike receptor-binding domain from different variants with chaga mushroom terpenoids.

Terpenoids from the chaga mushroom have been identified as potential antiviral agents against SARS-CoV-2. This is because it can firmly bind to the viral spike receptor binding domain (RBD) and the auxiliary host cell receptor glucose-regulated protein 78 (GRP78). The current work examines the association of the chaga mushroom terpenoids with the RBD of various SARS-CoV-2 variants, including alpha, beta, gamma, delta, and omicron. This association was compared to the SARS-CoV-2 wild-type (WT) RBD using molecular docking analysis and molecular dynamics modeling. The outcomes demonstrated that the mutant RBDs, which had marginally greater average binding affinities (better binding) than the WT, were successfully inhibited by the chaga mushroom terpenoids. The results suggest that the chaga mushroom can be effective against various SARS-CoV-2 variants by targeting both the host-cell surface receptor GRP78 and the viral spike RBD.Communicated by Ramaswamy H. Sarma.

Curative Potential of High-Value Phytochemicals on COVID-19 Infection.

Medicinal plants and their therapeutically promising chemical compounds belonging to the valued category of 'traditional medicine' are potential remedies for various health problems. Due to their complex structure and enormous health benefits, the high-value plant-derived metabolites collectively termed as 'phytochemicals' have emerged as a crucial source for novel drug discovery and development. Indeed, several medicinal plants from diverse habitats are still in the 'underexplored' category in terms of their bioactive principles and therapeutic potential. COVID-19, infection caused by the SARS-CoV-2, first reported in November 2019, resulted in the alarming number of deaths (6.61 million), was further declared 'pandemic', and spread of the disease has continued till today. Even though the well-established scientific world has successfully implemented vaccines against COVID-19 within the short period of time, the focus on alternative remedies for long-term symptom management and immunity boosting have been increased. At this point, interventions based on traditional medicine, which include medicinal plants, their bioactive metabolites, extracts and formulations, attracted a lot of attention as alternative solutions for COVID-19 management. Here, we reviewed the recent research findings related to the effectiveness of phytochemicals in treatment or prevention of COVID-19. Furthermore, the literature regarding the mechanisms behind the preventive or therapeutic effects of these natural phytochemicals were also discussed. In conclusion, we suggest that the active plant-derived components could be used alone or in combination as an alternative solution for the management of SARS-CoV-2 infection. Moreover, the structure of these natural productomes may lead to the emergence of new prophylactic strategies for SARS-CoV-2-caused infection.

Recent Advances in Antiviral Activities of Triterpenoids.

Triterpenoids, important secondary plant metabolites made up of six isoprene units, are found widely in higher plants and are studied for their structural variety and wide range of bioactivities, including antiviral, antioxidant, anticancer, and anti-inflammatory properties. Numerous studies have demonstrated that different triterpenoids have the potential to behave as potential antiviral agents. The antiviral activities of triterpenoids and their derivatives are summarized in this review, with examples of oleanane, ursane, lupane, dammarane, lanostane, and cycloartane triterpenoids. We concentrated on the tetracyclic and pentacyclic triterpenoids in particular. Furthermore, the particular viral types and possible methods, such as anti-human immunodeficiency virus (HIV), anti-influenza virus, and anti-hepatitis virus, are presented in this article. This review gives an overview and a discussion of triterpenoids as potential antiviral agents.

In-Silico Investigation Based Plant Secondary Metabolites as Promising Immunostimulants against Covid-19

Objectives : The present study is focused to introduce a better preventive and treatment prospective to fight against the COVID-19 crisis by improving the immune system along with inhibiting the viral activity by a comprehensive review and supportive in-silico study.Methodology : The study was conducted with a systemic review on the phytochemicals possessing immunostimulatory potentiality, which was further supported by an in-silico investigation of thosephytocomponents in improving the immunity of the patient as well as in preventive measures which cancontribute a major part to manage the dangerous consequences of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2).Results : In in-silico study showed that scutellarein, hesperidin andbaicalin exhibited strong binding affinity with ACE2, PAK1, Protease by strong molecular interaction forming several hydrogen bonds.Conclusion : The present finding interprets scutellarein, hesperidin and baicalin to be potential herbal immune boosters with antiviral potentiality which are to be further explored by in-vitro and in-vivo methods.

Lutein and astaxanthin as dietary support of therapy

Lutein and astaxanthin belong to carotenoids which have wide applications in food, nutraceutical and pharmaceutical industries. The total chemical syntheses of lutein and astaxanthin produces a mixture of stereoisomers. Both carotenoids are extracted from the plant material as the mixture of mono- and diesters. Lutein is extracted from marigold and tagetes flowers. Lutein supplementation increases its concentration in blood serum and in the macula of the eye. There is increasing evidence that lutein is important in the prevention of age-related macular degeneration (AMD) and may improve eye health. Astaxanthin is extracted from the Haematococcus pluvialis algae. Due to its strong antioxidant, anti-inflammatory, and immunomodulatory properties, they can be used to support the treatment of neurodegenerative and cardiovascular diseases, diabetes, eye diseases, and to supplement the diet of COVID-19 patients.

Impact of lycopene and astaxanthin on hematological and immunological parameters of laying hens

The aim of this study was to determine the hematological profile and specific immunity of laying hens with the addition of oil extracts of lycopene or astaxanthin to the diet. The study used High Line W36 chickens that were vaccinated against Newcastle disease, infectious bronchitis, avian rhinotracheitis and egg drop syndrome. It was found that the addition of lycopene (20 mg/kg) and astaxanthin (10 mg/kg) for 30 days did not affect the hematological profile of laying hens. Increasing the content of lycopene to 40 and 60 mg/kg or astaxanthin to 20 or 30 mg/kg of feed for 30 days reduced the number of leukocytes and hemoglobin in the blood compared to the control, which received an equivalent amount of refined sunflower oil in the diet. Lycopene and astaxanthin supplements, regardless of dose and duration of administration, did not affect the titer of antibodies to Newcastle disease, infectious bronchitis, avian rhinotracheitis, and egg drop syndrome in serum of vaccinated laying hens. The obtained data can be used to justify the optimal dose and term of feeding of lycopene or astaxanthin supplements in the development of a model of carotenoid enrichment of chicken egg yolks.

Nanoscale Technologies in the Fight against COVID-19: From Innovative Nanomaterials to Computer-Aided Discovery of Potential Antiviral Plant-Derived Drugs.

The last few years have increasingly emphasized the need to develop new active antiviral products obtained from artificial synthesis processes using nanomaterials, but also derived from natural matrices. At the same time, advanced computational approaches have found themselves fundamental in the repurposing of active therapeutics or for reducing the very long developing phases of new drugs discovery, which represents a real limitation, especially in the case of pandemics. The first part of the review is focused on the most innovative nanomaterials promising both in the field of therapeutic agents, as well as measures to control virus spread (i.e., innovative antiviral textiles). The second part of the review aims to show how computer-aided technologies can allow us to identify, in a rapid and therefore constantly updated way, plant-derived molecules (i.e., those included in terpenoids) potentially able to efficiently interact with SARS-CoV-2 cell penetration pathways.

Modern drug discovery applications for the identification of novel candidates for COVID-19 infections.

In early December 2019, a large pneumonia epidemic occurred in Wuhan, China. The World Health Organization is concerned about the outbreak of another coronavirus with the powerful, rapid, and contagious transmission. Anyone with minor symptoms like fever and cough or travel history to contaminated places might be suspected of having COVID-19. COVID-19 therapy focuses on treating the disease's symptoms. So far, no such therapeutic molecule has been shown effective in treating this condition. So the treatment is mostly supportive and plasma. Globally, numerous studies and researchers have recently started fighting this virus. Vaccines and chemical compounds are also being investigated against infection. COVID-19 was successfully diagnosed using RNA detection and very sensitive RT-PCR (reverse transcription-polymerase chain reaction). The evolution of particular vaccinations is required to reduce illness severity and spread. Numerous computational analyses and molecular docking have predicted various target compounds that might stop this condition. This paper examines the main characteristics of coronavirus and the computational analyses necessary to avoid infection.

Exploring the Mangrove Fruit: From the Phytochemicals to Functional Food Development and the Current Progress in the Middle East.

Nowadays, the logarithmic production of existing well-known food materials is unable to keep up with the demand caused by the exponential growth of the human population in terms of the equality of access to food materials. Famous local food materials with treasury properties such as mangrove fruits are an excellent source to be listed as emerging food candidates with ethnomedicinal properties. Thus, this study reviews the nutrition content of several edible mangrove fruits and the innovation to improve the fruit into a highly economic food product. Within the mangrove fruit, the levels of primary metabolites such as carbohydrates, protein, and fat are acceptable for daily intake. The mangrove fruits, seeds, and endophytic fungi are rich in phenolic compounds, limonoids, and their derivatives as the compounds present a multitude of bioactivities such as antimicrobial, anticancer, and antioxidant. In the intermediary process, the flour of mangrove fruit stands as a supplementation for the existing flour with antidiabetic or antioxidant properties. The mangrove fruit is successfully transformed into many processed food products. However, limited fruits from species such as Bruguiera gymnorrhiza, Rhizophora mucronata, Sonneratia caseolaris, and Avicennia marina are commonly upgraded into traditional food, though many more species demonstrate ethnomedicinal properties. In the Middle East, A. marina is the dominant species, and the study of the phytochemicals and fruit development is limited. Therefore, studies on the development of mangrove fruits to functional for other mangrove species are demanding. The locally accepted mangrove fruit is coveted as an alternate food material to support the sustainable development goal of eliminating world hunger in sustainable ways.

Contribution of the herbarium of the national center of floristics of Cote d'Ivoire in the fight against the symptoms caused by the COVID-19 disease: a bibliographic synthesis

This study was undertaken to identify herbal remedies that may be involved in the symptomatic management of COVID-19 disease. From a list of 247 medicinal plants, a bibliographic study was carried out with the richness, the floristic composition, the methods of preparation and use and the active principles of the plants as a variable. The importance value of these plants was also calculated. A Principal Component Analysis showed the links between the parts of plants used, the methods of preparation, the symptoms of COVID-19 disease that can be treated and the active ingredients. The results show that 226 medicinal plants divided into 190 genera and 79 families can be used to treat the symptoms of COVID- 19 disease namely otolaryngologic signs, pulmonary signs and general signs. Of these, twenty-eight (28) can relieve the majority of symptoms of COVID-19 disease. These symptoms are rhinorrhea, cough, fever, headache, vomiting, diarrhea, and muscle aches. These plants are mainly prepared in the form of a decoction and administered mainly orally. They mainly contain flavonoids, coumarins, alkaloids, tannins, steroids, terpenoids, saponosides, essential oils, mucilages, quinones, coumarins. The importance value of these plants is between 85.71 and 57.14%. The results also showed that eight (8) groups of medicinal plants can be distinguished according to the organs used, the methods of preparation, the symptoms of the COVID-19 disease treated and the active ingredients. The results of this study could serve as a database for the formulation of improved traditional drugs in the management of symptoms of COVID-19 disease in Cote d'Ivoire.

Pharmacokinetics and molecular docking study of siddha polyherbal preparation shailam against COVID-19 mutated S gene

COVID-19 is a deadly disease;at the time of the first COVID-19 wave (January 2020 to November 2020), so many deaths were reported worldwide. There were no standard conventional treatments and vaccines, so the whole world turned to traditional medicine. Siddha system of medicine is one of the traditional medicines practiced in the southern part of India. Shailam is a polyherbal formulation (licence no. 1189/25D) which was analyzed by molecular docking, with AutoDockVina software, against SARS-CoV-2 Spike Protein (PDB ID 7DDD). Absorption, distribution, metabolism, and excretion (ADME) properties were also recorded for Shailams phytocompounds using the online SwissADME tool. The results of the molecular docking study showed that the phytocompounds, like Caryophyllene, Aspidospermidin-17-ol, N,N Dibenzylidene-3,3-dichlorobenzidine, Beta-selinene, Curzerene, Germacrene B, Spathulenol, had the highest docking scores: -6.6 Kcal/mol, -8.8 Kcal/mol, -8.7 Kcal/mol, -6.2 Kcal/mol, -6.0 Kcal/mol, -6.6 Kcal/mol, -6.5 Kcal/mol, respectively, and the scores fall within the docking score range of the four standard conventional drugs;Azithromycin, Hydroxychloroquinone, Ivermectin, and Remdesivir which had binding energies of 7.7 Kcal/mol, -5.9 Kcal/mol, -9.2 Kcal/mol, and -7.5 Kcal/mol, respectively. ADME analysis predicted that all of Shailams phytocompounds met four Lipinskis rule of five and have a higher bioavailability score (0.55) as compared to standard conventional drugs, Azithromycin, Hydroxychloroquinone, Ivermectin, and Remdesivir (0.17). Twelve of Shailams phytochemical compounds have high GIT absorption and can cross the blood-brain barrier (BBB). In conclusion, Shailams phytocompounds show a good docking score and ADME property against SARS-CoV-2 Spike Protein (PDB ID 7DDD) as compared to standard conventional drugs.

Immunomodulatory properties of triterpenes.

The immune system is one of the main defence mechanisms of the human body. Inadequacy of this system or immunodeficiency results in increased risk of infections and tumours, whereas over-activation of the immune system causes allergic or autoimmune disorders. A well-balanced immune system is important for protection and for alleviation of these diseases. There is a growing interest to maintain a well-balanced immune system, especially after the Covid-19 pandemic. Many biological extracts, as well as natural products, have become popular due to their wide array of immunomodulatory effects and influence on the immune system. Triterpenes, one of the secondary metabolite groups of medicinal plants, exhibit immunomodulatory properties by various mechanisms. Different triterpenes, including components of commonly consumed plants, can promote some protection and alleviation of disease symptoms linked with immune responses and thus enhance overall well-being. This review aims to highlight the efficacy of triterpenes in light of the available literature evidence regarding the immunomodulatory properties of triterpenes. We have reviewed widely investigated immunomodulatory triterpenes; oleanolic acid, glycyrrhizin, glycyrrhetinic acid, pristimerin, ursolic acid, boswellic acid, celastrol, lupeol, betulin, betulinic acid, ganoderic acid, cucumarioside, and astragalosides which have important immunoregulatory properties. In spite of many preclinical and clinical trials were conducted on triterpenes related to their immunoregulatory actions, current studies have several limitations. Therefore, especially more clinical studies with optimal design is essential.

Phytochemical screening, GCMS profile, and in-silico properties of bioactive compounds in methanolic leaf extracts of Moringa oleifera

Plant Based Natural Products (PBNPs) have been subject of interest since ancient time due to their use in food, industrial and biomedical applications. Research attention has further augmented to explore their phytochemical composition, properties, and potential application in the post-COVID era. In the present study phytochemical screening has been carried out with Methanolic Leaf Extracts of Moringa oleifera (MLEMO) followed by Gas Chromatography-Mass Spectrometry (GCMS) analysis. Phytochemical analysis of MLEMO revealed the presence of Alkaloids, Carbohydrates, Coumarins, Flavonoids, Glycosides, Phenol, Proteins, Quinones, Saponins, Steroids, Tannins and Terpenoids. Further, GCMS analysis revealed the presence of 41 compounds of which Dihydroxyacetone;Monomethyl malonate;4H-Pyran-4-one,2,3-dihydro- 3,5-dihydroxy-6-methyl;1,3-Propanediol, 2-ethyl-2-(hydroxymethyl);Propanoic acid, 2- methyl-, octyl ester;3-Deoxy-d-mannoic lactone;Sorbitol;Inositol;Cyclohexanemethanol, alpha-methyl-4-(1-methylethyl), Hexadecanoic acid, Methyl palmitate;n-Hexadecanoic acid (Palmitic acid);9-Octadecenoic acid, methyl ester;Phytol;9,12,15-Octadecatrienoic acid;Octadecanoic acid;9-Octadecenamide were prominent. Most of the compounds in the list are bioactive and possess medicinal properties that are expected to serve as a baseline lead for the development of therapeutic agents.

Pharmacophore based virtual screening for natural product database revealed possible inhibitors for SARS-COV-2 main protease.

The challenge continues globally triggered by the absence of an approved antiviral drug against COVID-19 virus infection necessitating global concerted efforts of scientists. Nature still provides a renewable source for drugs used to solve many health problems. The aim of this work is to provide new candidates from natural origin to overcome COVID-19 pandemic. A virtual screening of the natural compounds database (47,645 compounds) using structure-based pharmacophore model and molecular docking simulations reported eight hits from natural origin against SARS-CoV-2 main proteinase (Mpro) enzyme. The successful candidates were of terpenoidal nature including taxusabietane, Isoadenolin A & C, Xerophilusin B, Excisanin H, Macrocalin B and ponicidin, phytoconstituents isolated from family Lamiaceae and sharing a common ent-kaurane nucleus, were found to be the most successful candidates. This study suggested that the diterpene nucleus has a clear positive contribution which can represent a new opportunity in the development of SARS-CoV-2 main protease inhibitors.

Interference of Chaga mushroom terpenoids with the attachment of SARS-CoV-2; in silico perspective.

Finding a potent inhibitor to the pandemic SARS-CoV-2 is indispensable nowadays. Currently, in-silico methods work as expeditious investigators to screen drugs for possible repurposing or design new ones. Targeting one of the possible SARS-CoV-2 attachment and entry receptors, Glucose-regulated protein 78 (GRP78), is an approach of major interest. Recently, GRP78 was reported as a recognized representative in recognition of the latest variants of SARS-CoV-2. In this work, molecular docking and molecular dynamics simulations were performed on the host cell receptor GRP78. With its many terpenoid compounds, Chaga mushroom was tested as a potential therapeutic against the SARS-CoV-2 receptor, GRP78. Results revealed low binding energies (high affinities) toward the GRP78 substrate-binding domain ß (SBDß) of Chaga mushroom terpenoids. Even the highly specific cyclic peptide Pep42, which selectively targeted GRP78 over cancer cells in vivo, showed lower binding affinity against GRP78 SBDß compared to the binding affinities of terpenoids. These are auspicious results that need to be tested experimentally. Intriguingly, terpenoids work as a double sword as they can be used to interfere with VUI 202,012/01, 501.V2, and B.1.1.248 variants of SARS-CoV-2 spike recognition.

Plant Terpenoids as Hit Compounds against Trypanosomiasis.

Human African trypanosomiasis (sleeping sickness) and American trypanosomiasis (Chagas disease) are vector-borne neglected tropical diseases, caused by the protozoan parasites Trypanosoma brucei and Trypanosoma cruzi, respectively. These diseases were circumscribed to South American and African countries in the past. However, human migration, military interventions, and climate changes have had an important effect on their worldwide propagation, particularly Chagas disease. Currently, the treatment of trypanosomiasis is not ideal, becoming a challenge in poor populations with limited resources. Exploring natural products from higher plants remains a valuable approach to find new hits and enlarge the pipeline of new drugs against protozoal human infections. This review covers the recent studies (2016-2021) on plant terpenoids, and their semi-synthetic derivatives, which have shown promising in vitro and in vivo activities against Trypanosoma parasites.

Chemical constituents and biological activities of Artemisia argyi H.Lév. & vaniot.

Artemisia argyi is a widely distributed and inexpensive plant resource, and study on its chemical compositions and biological activities will provide an important basis for its food applications and pharmaceutical developments. In this study, fourteen known guaiane-type sesquiterpenes (1-14), four known eudesmane-type sesquiterpenes (15-18), two known germacranolide-type sesquiterpenes (19, 20), and eight other types of terpenoids (20-28) were isolated from the leaves of A. argyi by polyamide and ODS CC and HPLC. The structures of all compounds are determined by 1 D NMR (1H-NMR、13C-NMR) and literature comparison. Among them, compounds 1 and 8 were isolated from Chinese folk medicine A. argyi for the first time. Besides, the LPS-induced RAW264.7 cell model has been evaluated the anti-inflammatory activities in vitro by the Griess reagent. The results indicated that the guaianolide sesquiterpenoids obtained from A. argyi have an excellent ability to inhibit NO production, especially Argyin A, a guaianolide sesquiterpenoid with isovaleryloxy substitution.

Revisiting the Antiviral Efficacy of Terpenoids: Plausible Adjunct Therapeutics for Novel SARS-CoV-2?

Presently the world is witnessing the most devastating pandemic in the history of mankind caused by Severe Acute Respiratory Syndrome or SARS-CoV-2. This dreaded pandemic is responsible for escalated mortality rates across the globe and this is the worst catastrophe in the history of mankind. Since its outbreak, substantial scientific explorations focusing on the formulation of novel therapeutical and/or adjunct intervention against the disease are continuously in the pipeline. However, till date, no effective therapy has been approved and hence the present alarming situation urges the necessity of exploring novel, safe and efficient interventional strategies. Functionally, terpenoids are a class of secondary plant metabolites having multi facet chemical structures and are categorically documented to be the largest reservoir of bioactive constituents, predominant in nature. Intriguingly, very little is scientifically explored or reviewed in regards to the anti-CoV-2 attributes of terpenoids. The present article thus aims to revisit the antiviral efficacy of terpenoids by reviewing the current scientific literature and thereby provide an opinion on the plausibility of exploring them as potential therapeutical intervention to deal with ongoing CoV-2 pandemic.