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.

Potential Health Survey of Traditional Spices & Herbs in Prevention and Treatment of COVID-19: A Review

The coronavirus (COVID-19) is a global public health pandemic disease emerged from the novel strain of the coronavirus 2 (SARS-CoV-2) that caused severe acute respiratory syndrome. It is the most significant respiratory illness that has affected the world since World War II. Currently, there is no globally approved drug for the treatment of pandemic COVID-19 except for some recently approved vaccines. Instead, various non-specific treatment options are being utilized by different countries. While some of these are effective, there is a lack of well-documented studies on the impact of traditional medicines on the management of SARS-CoV-2 in vitro and in silico. For thousands of years, traditional healers have been using various herbs and spices products and dietary plants to treat various diseases. This review aims to provide information on the use of traditional spices & herbs in COVID-19 protection and treatment and present the main characteristics of these products and their potential antiviral actions. Various databases were searched for articles related to the use of various herbs for the treatment of viral infections. Many of these studies show that various plant compounds can be utilized for the treatment of viral infections. This study aims to summarize the common used of herbal products and dietary supplements with potent bioactive compounds in treatment or prevent of COVID-19.

Cannabis as antivirals.

Cannabis is a plant notorious for its psychoactive effect, but when used correctly, it provides a plethora of medicinal benefits. With more than 400 active compounds that have therapeutic properties, cannabis has been accepted widely as a medical treatment and for recreational purposes in several countries. The compounds exhibit various clinical benefits, which include, but are not limited to, anticancer, antimicrobial, and antioxidant properties. Among the vast range of compounds, multiple research papers have shown that cannabinoids, such as cannabidiol and delta-9-tetrahydrocannabinol, have antiviral effects. Recently, scientists found that both compounds can reduce severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral infection by downregulating ACE2 transcript levels and by exerting anti-inflammatory properties. These compounds also act as the SARS-CoV-2 main protease inhibitors that block viral replication. Apart from cannabinoids, terpenes in cannabis plants have also been widely explored for their antiviral properties. With particular emphasis on four different viruses, SARS-CoV-2, human immunodeficiency virus, hepatitis C virus, and herpes simplex virus-1, this review discussed the role of cannabis compounds in combating viral infections and the potential of both cannabinoids and terpenes as novel antiviral therapeutics.

Herbal Medicines as Potential Inhibitors of SARS-CoV-2 Infection.

Coronavirus disease 2019 (COVID-19) is the result of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding molecular pathogenesis is an essential factor for the allocation of effective preventive measures and the development of targeted therapeutics against COVID-19. The genome of SARS-CoV-2 encodes structural and nonstructural proteins, which can be targets for compounds with potential therapeutic ability. On the other hand, the virus life cycle has stages susceptible to targeting by drug compounds. Many natural antiviral compounds have been studied and evaluated at the cellular and molecular levels with antiviral potential. Meanwhile, many studies over the past few months have shown that plant polysaccharides have a good ability to target proteins and stages of the virus life cycle. In this regard, in this review study, the virus specifications and infectious process and structural and functional components of SARSCoV- 2 will be reviewed, and then the latest studies on the effect of plant compounds with more focus on polysaccharides on viral targets and their inhibitory potential on the infectious process of COVID-19 will be discussed.

Recent advances on SOA formation in indoor air, fate and strategies for SOA characterization in indoor air - A review.

Recent studies proves that indoor air chemistry differs in many aspects from atmospheric one. People send up to 90 % of their life indoors being exposed to pollutants present in gas, particle and solid phase. Particle phase indoor is composed of particles emitted from various sources, among which there is an indoor source - secondary chemical reactions leading to formation of secondary organic aerosol (SOA). Lately, researchers' attentions turned towards the ultrafine particles, for there are still a lot of gaps in knowledge concerning this field of study, while there is evidence of negative influence of ultrafine particles on human health. Presented review sums up current knowledge about secondary particle formation in indoor environment and development of analytical techniques applied to study those processes. The biggest concern today is studying ROS, for their lifetime in indoor air is very short due to reactions at the very beginning of terpene oxidation process. Another interesting aspect that is recently discovered is monoterpene autooxidation process that leads to HOMs formation that in turn can influence SOA formation yield. A complex studies covering gas phase and particle phase characterization, but also toxicological studies are crucial to fully understand indoor air chemistry leading to ultrafine particle formation.

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.

Anxiolytic effect of Anthemis nobilis L. (roman chamomile) and Citrus reticulata Blanco (tangerine) essential oils using the light-dark test in zebrafish (Danio rerio).

ETHNOPHARMACOLOGICAL RELEVANCE: The anxiety disorders are the most prevalent mental health condition, and anxiety is considered the sixth cause of disability surpassing diabetes mellitus, chronic obstructive pulmonary disease, and osteoarthritis. Besides, the COVID-19 pandemic provided an increase in the number of psychiatric diseases diagnosis in all social layers around the world. About 55%-94% of patients diagnosed with anxiety disorders are treated with benzodiazepines, meanwhile benzodiazepines can promote several adverse effects. In this way, alternative therapies, such as essential oils may offer significant benefits in the treatment of patients with anxiety disorders. However, the anxiolytic effect of these essential oils must be proper evaluated appropriate as well as the suitable dosage and side effect need further research. AIM OF THE STUDY: The aim was to evaluate the anxiolytic effect of Roman chamomile (Anthemis nobilis L.) and tangerine (Citrus reticulata Blanco) essential oils using the light-dark test in adult zebrafish (Danio rerio). MATERIAL AND METHODS: Both essential oils were analyzed by GC-MS and the major compounds were identified. The anxiolytic effect was evaluated by light-dark test in adult zebrafish. RESULTS: The results showed that roman chamomile essential oil has anxiolytic effect in adult zebrafish, whereas tangerine essential oil tends to reduce anxiety The major compounds of tangerine essential oil were limonene and γ-terpinene, and the major compounds of roman chamomile were pentadecyl-3-methyl-2-butenoate, hexadecyl-3-methyl-2-butenoate, 1-piperidinol and trans-1-ethyl-3-methyl-cyclopentane. CONCLUSIONS: The present study demonstrated that this anxiolytic effect may be attributed to the synergistic effect of the compounds present in roman chamomile essential oil, particularly the major compounds. The roman chamomile essential oil at the highest concentration showed anxiolytic effect. The tangerine essential oil showed a tendency to reduce anxiety, but it was not statistically significative. In addition, roman chamomile and tangerine essential oils did not cause cause alteration in locomotion activity and exploratory ability of the fish.

Marine Microbial Diversity as Source of Bioactive Compounds

Four new cytotoxic indole-diterpenoids (penerpenes K-N), along with twelve other known compounds, have been discovered by Dai et al. from the fermentation broth produced by adding L-tryptophan to the culture medium of Penicillium sp. Three compounds (penerpene N, epipaxilline, emindole SB) were found to be cytotoxic to cancer cell lines, of which the known compound, epipaxilline, was the most active and showed cytotoxic activity against the human liver cancer cell line BeL-7402 with an IC50 value of 5.3 μM. Moreover, six compounds, namely paxilline, 7-hydroxyl-13-dehydroxypaxilline, 7-hydroxypaxilline-13-ene, 4a-demethylpaspaline-4a-carboxylic acid, PC-M6 and emindole SB, showed antibacterial activities against Staphylococcus aureus ATCC 6538 and Bacillus subtilis ATCC 6633 [3]. [...]the authors of this manuscript have also reported, for the first time, a putative lysosomal acid lipase produced by a green microalgae [7]. In this review, the authors have summarized the list of 145 natural products isolated from microorganisms associated with sea cucumbers between 2000 and 2021, which include polyketides, alkaloids and terpenoids as well as their reported biological activities [8].

Antimicrobial Activity of Aspergillus sp. from the Amazon Biome: Isolation of Kojic Acid

The antimicrobial potential of Aspergillus sp., isolated from the Amazon biome, which is stored at the Amazon Fungi Collection-CFAM at ILMD/FIOCRUZ, was evaluated. The fungal culture was cultivated in yeast extract agar and sucrose (YES) for cold extraction of the biocompounds in ethyl acetate at 28 °C for 7 days in a BOD type incubator. The obtained extract was evaluated for its antimicrobial activity against Candida albicans and Gram-positive and negative bacteria by the “cup plate” method and the determination of the minimum inhibitory concentration (MIC) by the broth microdilution method. The extract was subjected to thin layer chromatography (TLC) and fractionated by open and semipreparative column chromatography. The fractions of interest had their chemical constituents elucidated by nuclear magnetic resonance and mass spectrometry. The elucidated molecule was evaluated for cytotoxicity against the human fibroblast strain (MRC5). The extract presented inhibitory activity against both Gram-positive and negative bacteria, with the range of inhibition halos from 5.3 to 14 mm in diameter and an MIC ranging from 500 to 15.6 μg/mL. Seventy-one fractions were collected and TLC analysis suggested the presence of substances with double bond groups: coumarins, flavonoids, phenolic, alkaloids, and terpenes. NMR and MS analyses demonstrated that the isolated molecule was kojic acid. The results of the cytotoxicity test showed that MRC5 cells presented viability at concentrations from 500 to 7.81 μg/mL. The kojic acid molecule of Aspergillus sp., with antibacterial activity and moderate toxicity at the concentrations tested, is a promising prototype of an alternative active principle of an antimicrobial drug.

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.

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.

Cannabidiol and Terpene Formulation Reducing SARS-CoV-2 Infectivity Tackling a Therapeutic Strategy.

In late 2019, COVID-19 emerged in Wuhan, China. Currently, it is an ongoing global health threat stressing the need for therapeutic compounds. Linking the virus life cycle and its interaction with cell receptors and internal cellular machinery is key to developing therapies based on the control of infectivity and inflammation. In this framework, we evaluate the combination of cannabidiol (CBD), as an anti-inflammatory molecule, and terpenes, by their anti-microbiological properties, in reducing SARS-CoV-2 infectivity. Our group settled six formulations combining CBD and terpenes purified from Cannabis sativa L, Origanum vulgare, and Thymus mastichina. The formulations were analyzed by HPLC and GC-MS and evaluated for virucide and antiviral potential by in vitro studies in alveolar basal epithelial, colon, kidney, and keratinocyte human cell lines. Conclusions and Impact: We demonstrate the virucide effectiveness of CBD and terpene-based formulations. F2TC reduces the infectivity by 17%, 24%, and 99% for CaCo-2, HaCat, and A549, respectively, and F1TC by 43%, 37%, and 29% for Hek293T, HaCaT, and Caco-2, respectively. To the best of our knowledge, this is the first approach that tackles the combination of CBD with a specific group of terpenes against SARS-CoV-2 in different cell lines. The differential effectiveness of formulations according to the cell line can be relevant to understanding the pattern of virus infectivity and the host inflammation response, and lead to new therapeutic strategies.

In silico molecular docking and molecular dynamics examination of Andrographis paniculata compounds of andrographolide, neoandrographolide, and 5-hydroxy-7,8,2',3'-tetramethoxyflavone inhibition activity to SARS-CoV-2 main protease

In this work, Andrographis paniculata compounds of Andrographolide, Neoandrographolide, and 5-hydroxy-7,8,2',3'-tetramethoxyflavone inhibition activity to SARS CoV-2 main protease were examined through in silico molecular docking and molecular dynamics simulation, with Remdesivir as control ligand. Docking score and MMGBSA were examined as well as molecular dynamics parameters: RMSD, RMSF and Protein ligand contact fraction. Our study found that Andrographis paniculata compounds of Andrographolide, Neoandrographolide, and 5-hydroxy-7,8,2',3'-tetramethoxyflavone have comparable inhibition activity to SARS CoV-2 main protease in comparison to Remdesivir. 5-hydroxy7,8,2',3'-tetramethoxyflavone has the lowest docking score, which was further validated by protein ligand contact fraction examination, although MMGBSA score is lowest for Remdesivir.

Non-Cannabinoid Metabolites of Cannabis sativa L. with Therapeutic Potential.

The cannabis plant (Cannabis sativa L.) produces an estimated 545 chemical compounds of different biogenetic classes. In addition to economic value, many of these phytochemicals have medicinal and physiological activity. The plant is most popularly known for its two most-prominent and most-studied secondary metabolites-Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Both Δ9-THC and CBD have a wide therapeutic window across many ailments and form part of a class of secondary metabolites called cannabinoids-of which approximately over 104 exist. This review will focus on non-cannabinoid metabolites of Cannabis sativa that also have therapeutic potential, some of which share medicinal properties similar to those of cannabinoids. The most notable of these non-cannabinoid phytochemicals are flavonoids and terpenes. We will also discuss future directions in cannabis research and development of cannabis-based pharmaceuticals. Caflanone, a flavonoid molecule with selective activity against the human viruses including the coronavirus OC43 (HCov-OC43) that is responsible for COVID-19, and certain cancers, is one of the most promising non-cannabinoid molecules that is being advanced into clinical trials. As validated by thousands of years of the use of cannabis for medicinal purposes, vast anecdotal evidence abounds on the medicinal benefits of the plant. These benefits are attributed to the many phytochemicals in this plant, including non-cannabinoids. The most promising non-cannabinoids with potential to alleviate global disease burdens are discussed.

Chemically Diverse and Biologically Active Secondary Metabolites from Marine Phylum chlorophyta.

For a long time, algal chemistry from terrestrial to marine or freshwater bodies, especially chlorophytes, has fascinated numerous investigators to develop new drugs in the nutraceutical and pharmaceutical industries. As such, chlorophytes comprise a diverse structural class of secondary metabolites, having functional groups that are specific to a particular source. All bioactive compounds of chlorophyte are of great interest due to their supplemental/nutritional/pharmacological activities. In this review, a detailed description of the chemical diversity of compounds encompassing alkaloids, terpenes, steroids, fatty acids and glycerides, their subclasses and their structures are discussed. These promising natural products have efficiency in developing new drugs necessary in the treatment of various deadly pathologies (cancer, HIV, SARS-CoV-2, several inflammations, etc.). Marine chlorophyte, therefore, is portrayed as a pivotal treasure in the case of drugs having marine provenience. It is a domain of research expected to probe novel pharmaceutically or nutraceutically important secondary metabolites resulting from marine Chlorophyta. In this regard, our review aims to compile the isolated secondary metabolites having diverse chemical structures from chlorophytes (like Caulerpa ssp., Ulva ssp., Tydemania ssp., Penicillus ssp., Codium ssp., Capsosiphon ssp., Avrainvillea ssp.), their biological properties, applications and possible mode of action.

In Vitro Evaluation of the Activity of Terpenes and Cannabidiol against Human Coronavirus E229.

The activity of a new, terpene-based formulation, code-named NT-VRL-1, against Human Coronavirus (HCoV) strain 229E was evaluated in human lung fibroblasts (MRC-5 cells), with and without the addition of cannabidiol (CBD). The main constituents in the terpene formulation used for the experiment were beta caryophyllene, eucalyptol, and citral. The tested formulation exhibited an antiviral effect when it was pre-incubated with the host cells prior to virus infection. The combination of NT-VRL-1 with CBD potentiated the antiviral effect better than the positive controls pyrazofurin and glycyrrhizin. There was a strong correlation between the quantitative results from a cell-viability assay and the cytopathic effect seen under the microscope after 72 h. To the best of our knowledge, this is the first report of activity of a combination of terpenes and CBD against a coronavirus.

Natural Substances and Semisynthetic Derivatives as Potential Alternative Products Against SARS-CoV-2.

BACKGROUND AND OBJECTIVE: Today, a new ß-coronavirus called SARS-CoV-2 has emerged and it is causing a global pandemic. Inter-human transmission studies have indicated a significant role of aerosols in the transmission of many respiratory viruses. Hence, it is very important to decrease the spread of the virus through disinfectant agents. This review aimed to provide an overview related to possible alternative inhibitory molecules against this virus. METHOD: The literature search was performed in the MEDLINE electronic database using the public access known as NCBI-PUBMED. Keywords "coronavirus" and "SARS-CoV-2" and "COVID19" were used. No specific time range was used. RESULTS: We provide a review related to structure, anti-coronavirus activity and molecular mechanism of natural substances and semisynthetic derivatives such as glycopeptides, lipopeptides, probiotics, surfactants, terpenes and resveratrol. We also include the latest in vitro experiments with anti-SARSCoV- 2 activity. We also provide the theoretical basis for discussing the prospects of such natural molecules as possible alternative anti-Coronavirus products, so as to develop a complete screening for future applications. CONCLUSION: In summary, this review suggest to investigate deeper several molecules most of which belong to natural substances to fight COVID19 disease.

Can limonene be a possible candidate for evaluation as an agent or adjuvant against infection, immunity, and inflammation in COVID-19?

Coronavirus disease (COVID-19) caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing pandemic and presents a public health emergency. It has affected millions of people and continues to affect more, despite the tremendous social preventive measures. The therapeutic strategy relies on suppressing infectivity and inflammation, along with immune modulation. The identification of candidate drugs effective for COVID-19 is crucial, thus many natural products including phytochemicals are also being proposed for repurposing and evaluated for their potential in COVID-19. Among numerous phytochemicals, limonene (LMN), a dietary terpene of natural origin has been recently showed to target viral proteins in the in-silico studies. LMN is one of the main compounds identified in many citrus plants, available and accessible in diets and well-studied for its therapeutic benefits. Due to dietary nature, relative safety and efficacy along with favorable physicochemical properties, LMN has been suggested to be a fascinating candidate for further investigation in COVID-19. LMN showed to modulate numerous signaling pathways and inhibits inflammatory mediators, including cytokines, chemokines, adhesion molecules, prostanoids, and eicosanoids. We hypothesized that given the pathogenesis of COVID-19 involving infection, inflammation, and immunity, LMN may have potential to limit the severity and progression of the disease owing to its immunomodulatory, anti-inflammatory, and antiviral properties. The present article discusses the possibilities of LMN in SARS-CoV-2 infections based on its immunomodulatory, anti-inflammatory, and antiviral properties. Though, the suggestion on the possible use of LMN in COVID-19 remains inconclusive until the in-silico effects confirmed in the experimental studies and further proof of the concept studies. The candidature of LMN in COVID-19 treatment somewhat appear speculative but cannot be overlooked provided favorable physiochemical and druggable properties. The safety and efficacy of LMN are necessary to be established in preclinical and clinical studies before making suggestions for use in humans.