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.

COVID-19 Therapeutic Potential of Natural Products.

Despite the fact that coronavirus disease 2019 (COVID-19) treatment and management are now considerably regulated, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still one of the leading causes of death in 2022. The availability of COVID-19 vaccines, FDA-approved antivirals, and monoclonal antibodies in low-income countries still poses an issue to be addressed. Natural products, particularly traditional Chinese medicines (TCMs) and medicinal plant extracts (or their active component), have challenged the dominance of drug repurposing and synthetic compound libraries in COVID-19 therapeutics. Their abundant resources and excellent antiviral performance make natural products a relatively cheap and readily available alternative for COVID-19 therapeutics. Here, we deliberately review the anti-SARS-CoV-2 mechanisms of the natural products, their potency (pharmacological profiles), and application strategies for COVID-19 intervention. In light of their advantages, this review is intended to acknowledge the potential of natural products as COVID-19 therapeutic candidates.

Glycyrrhizin inhibits swine acute diarrhea syndrome coronavirus infection via the HMGB1/TLR4/JNK signal pathway

Swine acute diarrhea syndrome coronavirus (SADS-CoV), a newly discovered enteric coronavirus, is the etiological agent that causes severe clinical diarrhea and intestinal pathological damage in piglets. In this study, Vero E6 and IPI-2I cells were pretreated with different concentrations of glycyrrhizin (GLY) for 2 hours, and then infected with different concentrations of SADSCoV, aiming to investigate the inhibitory effect of GLY on SADS-CoV. Western blot and TCID50 results revealed a significantly decreased N protein expression and viral titer, indicating that GLY can inhibit the infection of SADS-CoV. Vero E6 and IPI-2I cells were pretreated with different concentrations of GLY for 2 hours and infected with SADS-CoV. Western blot results showed that when the concentration of GLY was 0.8 mmol/L, the expression of N protein decreased significantly, indicating that GLY inhibited the invasion of the virus. At first, cells were treated with 0.4 mmol/L GLY, and cell samples were collected at 2 hours, 6 hours and 12 hours after being infected with SADS-CoV for analysis, and the expression of N protein were found to be significantly reduced at all points, indicating that GLY had a significant inhibitory effect on the replication of the virus. GLY is a competitive inhibitor of high mobility group box 1 (HMGB1), and the receptors of HMGB1 mainly include TLR4 and RAGE. Based on this fact, the mutant plasmid at the key sites of HMGB1 (C45S, C106S, C45/106S) and the siRNA of the RAGE receptor were transfected to Vero E6 cells and infected with SADS-CoV, and the cell supernatant and samples were harvested. The western blot and TCID50 results showed that the expression of N protein and the virus titer were decreased, suggesting that GLY exerts its function by affecting the binding of HMGB1/TLR4/RAGE during SADS-CoV infection. To further explore the signaling pathway through which GLY functions, Vero E6 and IPI-2I cells were inoculated with SADS-CoV, and cell samples were harvested, western blot was used to detect the changes of MAPK proteins. The results showed that the protein expression levels of p-p38, p-JNK and p-ERK were up-regulated in the early and late stages, indicating that the MAPK pathway was activated by SADS-CoV infection. Vero E6 and IPI-2I were pretreated with different concentrations of GLY and TLR4 inhibitor TAK for 2 hours and infected with SADS-CoV. Protein samples were harvested and analysed by western blot which showed a decreased p-JNK and N proteins, while other proteins showed no significant changes. These results indicated that GLY and TAK regulated the phosphorylation of JNK but did not regulate the phosphorylation of p38 and ERK. Also, Vero E6 cells were treated with HMGB1 antibody, the siRNA of HMGB1 and HMGB1 mutants plasmid, and infected with SADS-CoV. Protein samples were harvested, western blot results showed that phosphorylation of JNK decreased, indicating that HMGB1 affected JNK phosphorylation. Finally, Vero E6 and IPI-2I cells were pretreated with different concentrations of JNK inhibitor SP600125 to infect SADS-CoV, western blot, TCID50 and IFA results showed that the expression of N protein and virus titer, as well as virus replication were reduced, indicating that SP600125 inhibited virus replication. In conclusion, our results revealed that GLY can inhibit in vitro replication of SADS- CoV, mainly through the HMGB1/TLR4/JNK signaling pathway. The discovery of this pathway provides theoretical support for the research of novel anti-SADS-CoV drugs.

In-silico screening of plant-derived natural compounds for their anti-COVID-19 potential

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China, in December 2019 and quickly spread across the worldwide. It becomes a global pandemic and risk to the healthcare system of almost every nation around the world. In this study thirty natural compounds of 19 Indian herbal plants were used to analyze their binding with eight proteins associated with COVID -19. Based on the molecular docking as well as ADMET analysis, isovitexin, glycyrrhizin, sitosterol, and piperine were identified as potential herbal medicine candidates. On comparing the binding affinity with Ivermectin, we have found that the inhibition potentials of the Trigonella foenum-graecum (fenugreek), Glycyrrhiza glabra (licorice), Tinospora cordifolia (giloy) and Piper nigrum (black pepper) are very promising with no side-effects.

Fostering home-grown response to COVID-19: development of improved traditional herbal medicines to WHO standards

Facing the unprecedented burden and rapid spread of the Covid-19 pandemic across the globe, responses from various regions have been exceptionally quick. Drug discovery has been essentially based on repurposing, particularly at the onset of the scourge. Several experimental models have been designed ranging from in vitro cell culture systems to nonhuman primates;however, each with advantages and limitations. It was revealed beside its detrimental consequences on health, economy and the society, Covid-19 has also provided opportunity to highlight the immense potential of traditional medicine as a valid alternative for addressing major health threat. The African traditional medicine has been instrumental for the control of the COVID-19 pandemic in the continent, in situation of extremely low vaccination coverage. For optimal and sustainable use of traditional medicine, we strongly recommend products be developed following the WHO standards, while taking into consideration sustainability, environmental protection and copyright issues surrounding the natural product-based drug research and development.

Evaluation of berberine pellet effect on clinical recovery time in COVID-19 outpatients: a pilot clinical trial

Objective: Severe disease onset of COVID-19 may result in alveolar injury and respiratory failure. Apoptosis and inflammation are the main causes of respiratory distress syndrome. Berberine is used in medicine as an analgesic, anti-asthmatic, anti-inflammatory, and antiviral. In the current investigation, the effect of berberine on COVID-19 outpatients was studied. Materials and Methods: The present clinical trial was performed on 40 outpatients who were randomly assigned to berberine (300 mg, TID, 2 weeks) (n=19) or placebo groups (n=21). Both groups received standard therapy and they were monitored on days 3, 7, and 14 after the beginning of the therapy for clinical symptoms' improvement, quantitative CRP, lymphopenia, CBC, and SpO2. The severity and frequency of these symptoms and the level of the parameters were statistically compared between the two groups. Results: On days 0, 3, 7, and 14, there was no significant difference between the berberine and placebo groups in the improvement of clinical symptoms (cough, shortness of breath, nausea, loss of smell and taste, diarrhea, dizziness, sore throat, stomachache, body aches, and body temperature), quantitative CRP, lymphopenia, WBC, neutrophils, platelets, or SpO2. Conclusion: Berberine (300 mg, TID, two weeks) is ineffective in treating COVID-19. More research with a larger sample size is needed to investigate different berberine dosages in other pharmaceutical formulations.

Anti-viral compounds from Jatropha curcas seed extract with anti-HIV-1 and anti-SARS-CoV-2 action

Many studies have dealt with the medicinal properties of Jatropha curcas;however, there are limited studies on the scope of its antiviral potential. This is a fact associated with the current challenges posed by HIV-AIDS and COVID-19, which has reinforced the need to expand the knowledge about its antiviral resource. Based on the search for natural products with anti-HIV-1 and anti-SARS-CoV-2 activities, this work analyzed the extract of J. curcas seed, the structure of the plant whose antiviral references were not found in the literature, and the compounds that can potentiate it as a candidate for herbal medicine. GC-MS analysis was used to screen for the active substances of the J. curcas seeds, and the literature was searched to find those with anti-HIV-1 and anti-SARS-CoV-2 indication. The results showed they have 27 compounds, of which glycerol 1-palmitate, stigmasterol and gamma-sitosterol were shown to have antiviral action in the literature. Regarding glycerol 1-palmitate, no detailed description of its antiviral action was found. Stigmasterol and gamma-sitosterol act as anti-HIV-1 and anti-SARS-CoV-2, respectively, inhibiting the reverse transcriptase of HIV-1, the proteases 3CLpro, PLpro and the spike proteins of SARS-CoV-2. However, despite the fact that the extract of J. curcas seeds consist of antiviral compounds that fight against the etiological agents of HIV-AIDS and COVID-19, it is concluded that there is a need to deepen this evidence, by in vitro and in vivo assays.

Ethnobotanical study on the use of medicinal plants with antiviral interest, case of SARS-CoV-19, in the region of Seraidi (Annaba, north-east Algeria)

The taxonomic diversity and the richness of the region of Seraidi (North-East Algeria) in medicinal plants, as well as the appearance of diseases of viral origin, in particular, the current pandemic of SARS-CoV-2, led us to the realization of an ethnobotanical survey of plants with antiviral interests. The survey was conducted based on a pre-established quiz, with 120 people from different categories of the population of Seraidi, with the aim of listing the medicinal plants used in the treatment of viral diseases and collecting as much information as possible on this subject. After analyzing, the information provided by the people interviewed, we listed 32 species belonging to 20 families, of which the Lamiaceae family is the most represented. Older women are the most affected by the use of plants;people without a higher intellectual level have the most knowledge about the use of plants with antiviral interest. The leaf is the most widely used organ, in the form of a decoction or infusion, administered orally.

Synthesis, characterization and pharmacological activities of silver nanoparticles using leaves extract of turmeric plant

In present manuscript describes synthesis of silver nanoparticles using turmeric leaves extract, traditional turmeric is a common spice that comes from the root of Curcuma longa, chemical called curcumin. Turmeric has a warm, bitter taste and is frequently used to flavor or color curry powders, mustards, butters, and cheeses. People commonly use turmeric for osteoarthritis, hay fever, depression, high cholesterol, liver disease, itching. There is also no good evidence to support using turmeric for COVID-19. Synthesis of silver nanoparticles AgNO powder was dissolved in distilled water to prepare 10 mM AgNO stock 3 3 solution from which different composition prepared. The AgNO solutions were mixed with urmeric plants 3 t leaves extract in equal proportion in flask. The flask was wrapped with an aluminum foil and was then heated in a water bath at 50-60 C for 2 hours. The synthesis of nanoparticles, which was confirmed by UVSpectra and TEM. UV-Vis spectra and visual observation showed that the color of the fresh leaf extractsof Vinca rosea turned into brownish yellow, respectively, after treatment with silver. In addition, TEM analysis confirmed that AgNO solutions for all concentrations produced ilver nanoparticles and their average size 3 s was less than 20 nm. Turmeric plants extract of fresh leaves can be used as bioreducing agents, drug resistant strains, toxic nature towards microbial agents, play an important role in nanoscience and nanotechnology, particularly in nanomedicine and potential applications in cancer diagnosis and therapy.

Improved virus inhibition by microencapsulated monoclonal antibody against porcine epidemic diarrhea virus

Porcine epidemic diarrhea virus (PEDV) has been affecting the swine industry, especially in suckling pigs in with a high mortality rate. Among all the strategies to overcome PEDV, boosting mucosal immunity in pig intestine via oral administration appears to be more efficient than other routes. However, there are biological obstacles such as acidic environment that could damage biologics, a product from organisms often used for PEDV treatment. The plant-derived 2C10 monoclonal antibody (mAb) from Nicotiana benthamiana produced by transient expression was revealed as one of the potential candidates against PEDV through oral delivery. Herein, we demonstrated the calcium-alginate microencapsulation system to protect the 2C10 mAb from the harsh condition in the stomach and to be released the 2C10 mAb when arriving in the intestine. The pH-responsive encapsulated 2C10 mAb microbeads were constructed from the calcium-alginate system. The microbeads were well-tolerated under the acidic environment of simulated gastric fluid (SGF) and were digested under the alkaline condition of simulated intestinal fluid (SIF). The encapsulated 2C10 mAb in the SPF-treated microbeads exhibited high virus neutralization efficiency in Vero cells when compared to the unencapsulated 2C10 mAb treated by SPF that cannot neutralize the virus. For these reasons, calcium-alginate microencapsulation system is an attractive platform to be considered as a candidate for the next generation of oral vaccine development.

Antiviral activitiy of curcumin, demethoxycurcumin, bisdemethoxycurcumin and cyclocurcumin compounds of Curcuma longa against NSP3 on SARS-CoV-2

SARS-CoV-2 genome encodes two large polyproteins (pp), pp1a and pp1ab which are cleaved and transformed into a mature form by a protease, non-structural protein 3 (NSP3). NSP3 is encoded by open reading frame (ORF) 1a/b. Curcuma longa (C. longa) or turmeric has been documented to have antiviral effects. The aim of this study was to assess the viral activities of C. longa against SARS-CoV-2 focusing on its potency to inhibit viral replication by targeting NSP3. PubChem databases were used to obtain the metabolic profile of C. longa. The compound's interaction with nucleocapsid was analyzed using molecular docking with Molegro Virtual Docker. Bioinformatics analysis based on rerank score presents all compounds of C. longa have higher binding affinity than the native ligand with cyclocurcumin as the lowest score (-128.38 kcal/mol). This anti-viral activity was hypothesized from the similarity of hydrogen bonds with amino acid residues Ser 128 and Asn 40 as key residues present in Ribavirin. This study reveals that C. longa is the potential to be developed as an antiviral agent through replication inhibition in SARS-CoV-2 targeting its replication mediated by NSP3.

The use of Ephedra herbs in the treatment of COVID-19

Objective: Ephedra herbs are the only extant genus in its family, Ephedraceae, and order, Ephedrales. It has been prescribed in traditional medicine for improving headaches and respiratory infections. On the other hand, because the coronavirus disease 2019 (COVID-19) causes respiratory problems and COVID-19 pandemic is the most widespread outbreak that has affected humanity in the last century, the current review aims using literature search to investigate the effects of the Ephedra herbs compounds on COVID-19 to supply a reference for its clinical application in the inhibition and remedy of COVID-19. Materials and Methods: This review was performed using articles published in various databases, including Web of Science, PubMed, Scopus, and Google Scholar, without a time limit. For this paper, the following keywords were used: "Ephedra", "coronavirus disease 2019", "COVID-19", "Severe acute respiratory syndrome coronavirus 2" or "SARS CoV 2". Results: The results of this review show that the Ephedra herbs have effectiveness on COVID-19 and its compounds can bind to angiotensin-converting enzyme 2 (ACE2) with a high affinity and act as a blocker and prevent the binding of the virus. Conclusion: Some plants used in traditional medicine, including the Ephedra herbs, with their active compounds, can be considered a candidate with high potential for the control and prevention of COVID-19.

In silico prediction of the inhibitory effect of phytochemical components extracted from Knautia sarajevensis on the main protease of SARS-CoV-2 virus

Essential role in replication and transcription of coronavirus makes the main protease of SARS-CoV-2 a great traget for drug design. The aim of this study was to predict structural interactions of compounds isolated from the Bosnian-Herzegovinian endemic plant Knautia sarajevensis (G. Beck) Szabo against the 3CLpro of SARS-CoV-2 virus. The three-dimensional crystal structure of SARS-CoV-2 main protease was retrieved from the RCSB Protein Data Bank and the three-dimensional structures of isolated compounds were obtained from the PubChem database. Active site was predicted using PrankWeb, while the preparation of protease and compounds was performed using AutoDock Tools and OpenBabel. Molecular docking was carried out using AutoDock Vina. Structural interactions are visualised and analyzed using PyMOL, LigPlus and UCSF Chimera. Apigenin, kaempferol, myricetin and quercetin showed the highest binding affinity for SARS-CoV-2 main protease and formed significant hydrogen bonds with the given protein. Results obtained in this study are in accordance with previous studies and showed that these compounds could potentially have antiviral effects against SARS-CoV-2. These findings indicate that K. sarajevensis could be potentially utilized as an adjuvant in the treatment of coronavirus disease 2019, but further pharmacological studies are required in order to prove the potential medicinal use of the plant.

Phytotherapy in the virus infections

The study is a review of natural raw materials that can prevent infection and help treat viral infections, including those that cause COVID-19. The condition of not getting infected with pathogens that cause infections of the upper and lower respiratory tract is high the body resistance. An important element that influences the proper immunity of the body is the diet. The functioning of the immune system is improved by bee products, and plant materials: purple coneflower herb, flower and root, licorice root, aloe gel and Baikal skullcap root, as well as black cumin seed oil, chaga mushroom, lemon balm leaves and chamomile flowers. Strengthening immunity is conducive to maintaining a good mood and reducing stress. The antiviral activity has been confirmed for many plant materials, especially those containing essential oils. Natural products can be used for prevention and treatment. The country that copes best with the coronavirus epidemic is China, thanks to a combination of academic and natural medicine. The study quotes an excerpt from the "Handbook of COVID-19 Prevention and Treatment", prepared by Chinese doctors, with particular attention to the recipes used by them.

Assessment of Antioxidant, Anti-Lipid Peroxidation, Antiglycation, Anti-Inflammatory and Anti-Tyrosinase Properties of Dendrobium sulcatum Lindl

Dendrobium sulcatum Lindl or "Ueang Jampa-Nan” (Orchidaceae family) is widely dis-tributed in Thailand and Laos. It is classified in the genus Dendrobium, which is used in both traditional Chinese medicine and Ayurvedic medicine for health enhancement and anti-aging. The purpose of this study was to investigate the phytochemical constituents and bioefficacy of stems, leaves and flowers from D. sulcatum for cosmetic and cosmeceutical applications. Phenolic and flavonoid contents were tested for the phytochemical evaluation. The antioxidant (DPPH, FRAP and ABTS assays), anti-lipid peroxidation, antiglycation, anti-inflammatory and anti-tyrosinase properties were assessed for their bioefficacy. The results showed that the extracts of stem and leaf had higher total phenolic content than that of the flower, and the leaf extract had the highest flavonoid content. The antioxidant, anti-lipid peroxidation and anti-inflammatory activities of the extracts were greater in those from the stem and leaf compared with that of the flower. The leaf extract exhibited the greatest antiglycation property. The results of anti-tyrosinase analysis of the extracts showed that the leaf and flower exhibited potent activities with a percentage inhibition greater than 70% (at a concentration of 50 µg/mL). In conclusion, these findings suggest that the ethanolic extracts from different parts of D. sulcatum are promising sources of natural active ingredients for further cosmetic and cosmeceutical products.

Effect of aqueous extract of violet on fever in patients with COVID-19: a randomized clinical trial

Background and purpose: Violet is a plant that has received interest in complementary medicine due to its anti-inflammatory, antipyretic, and antimicrobial effects. Fever is one of the major symptoms of COVID-19. This study was conducted to determine the effect of violet extract in the form of syrup on fever in patients with COVID-19. Materials and methods: In this randomized clinical trial, 52 patients with COVID-19 were studied in Intensive Care Unit in Amol Imam Khomeini Hospital (2021). In intervention group in addition to an injection of acetaminophen, 5 cc of violet extract syrup prepared from the aqueous extract of the plant was taken. The temperature was recorded after 30 and 60 minutes and four hours. The follow-up of the patients continued for three days and the temperature was recorded every six hours. Results: There was a significant difference between the intervention group (36.84..0.37) and control group (37.13..0.62) in mean temperature at second time in second day of follow-up (P=0.04). Also, the mean temperature was found to be significantly different between the two groups at 30 (P=0.001) and 60 minutes (P=0.05) after the intervention. At other groups, there was no significant difference between the intervention and control groups. Conclusion: The aqueous extract of violet plant in the form of syrup reduces fever in patients with COVID-19 causing no complication. Due to the ease of access to this herbal product, it can be used to prevent problems caused by fever.

A mini review on the prospects of Fagara zanthoxyloides extract based composites: A remedy for COVID-19 and associated replica?

Studies are still being conducted to find a sustainable and long-lasting solution to the lethal consequences of the feared virus characterized as coronavirus disease (Covid-19) and its accompanying pathogenic replication, which pose a serious threat to human survival in the wake of its broad distribution. Since its emergence, researchers have investigated synthetic approaches in search of a dependable vaccine or treatment and curtail the spread of the virus and also enhance the health of a patient who has been affected. Unfortunately, the infection is yet to be entirely eradicated in many parts of the world. Despite the introduction of synthetic pharmaceuticals like remdesivir and derivatives of chloroquine, plant extracts may be an alternative reliable strategy that could successfully combat the operation of the virus. Herein, we investigated the prospects of fagara zanthoxyloides lam. (rutaceae) (syn. zanthoxylum zanthoxyloides), a well-known medicinal tree whose extracts have demonstrated success in treating many microbiological and viral-related infections. The distinctive plant extracts contain several bioactive phytochemicals with promising biological activity with minimal or no side effects and are being researched for a variety of applications, particularly in the pharmaceutical and medicinal industries. Consequently, in this review, we examined the crude extracts from the Fagara species and suggested that careful consideration should be given to its independent use or combination with other bioactive molecules, such as biopolymers and nano-metallic composites, to combat the terrifying Covid-19 virus and its associates. © 2023 Walter de Gruyter GmbH, Berlin/Boston 2023.

The influence of dietary Salvia and lavender powders on productive performance, some physiological parameters, and immunity of broiler under stocking density stress

The purpose of this experiment was to increase poultry meat production by increasing the number of chickens reared in the same area and managing it by using medicinal herbs Salvia officinalis L and Lavandula angustifolia L. in the broiler chicken diet. 705 one-day-old chicks were randomly distributed into to7 treatments with three replicates for an area of two m2 floor system in each replicate for each treatment, during 35 days of the study. T0 negative control 75 chicks, 25 chicks for each replicate 12-13 chicks per m2 fed standard diet. T1 positive control (stocking density without supplementation)105 chicks, 35 each replicate chicks 17-18 per m2 fed standard diet. The same stocking density for T2, T3, T4, T5, and T6 have been given standard feed with supplemented herbals, salvia 0.7%, 0.9%, lavender0.7%, 0.9%, and mixed 0.7% respectively. Depending on the results, chickens reared in stress stocking density with supplementations led to higher improvement of body weight, meat production, body weight gain (BWG), feed conversion ratio(FCR g feed/g weight), production index PI, carcass weight (g) and dressing percentage, RBCs 106cells/mm3, lymphocyte%, of increasing activity of thyroid hormones T3, T4 (nmol/L) boost antibody titers of ND and IBV when compared with positive control. However, heterophil%, stress indicator H/L ratio, glucose mg/ dL and cholesterol mg/ dL significantly reduced. The results showed that adding sage and lavender plants to broiler feed is effective in improving productivity, immunity, and resistance characteristics in reducing the adverse effects of stress caused by increasing the intensity of broiler rearing in the same area.

Admetox-informatics of plant derived octadecanoic acid (stearic acid) from ethyl acetate fraction of Moringa oleifera leaf extract as a natural lead for next generation drug design, development and therapeutics

In-silico Computer-Aided Drug Design (CADD) significantly relies on cybernetic screening of Plant Based Natural Products (PBNPs) as a prime source of bioactive compounds/ drug leads due to their unique chemical structural scaffolds and distinct functional characteristic features amenable to drug design and development. In the Post-COVID-Era a large number of publications have focused on PBNPs. Moreover, PBNPs still remain as an ideal source of novel therapeutic agents of GRAS standard. However, a well-structured, in-depth ADME/Tox profile with deeper dimensions of PBNPs has been lacking for many of natural pharma lead molecules that hamper successful exploitation of PBNPs. In the present study, ADMET-informatics of Octadecanoic Acid (Stearic Acid - SA) from ethyl acetate fraction of Moringa oleifera leaves has been envisaged to predict ADMET and pharmacokinetics (DMPK) outcomes. This work contributes to the deeper understanding of SA as major source of drug lead from Moringa oleifera with immense therapeutic potential. The data generated herein could be useful for the development of SA as plant based natural product lead (PBNPL) for drug development programs.

Exploration on the potential mechanism of baicalein on Porcine Deltacoronavirus infection based on network pharmacology

This study aimed to explore the protective mechanism of baicalein against porcine deltacoronavirus (PDCoV) infection. The targets of baicalein were obtained through Pharmamapper, Pubchem, STITCH, TCMSP and Swiss Targer Prediction databases, and the targets of PDCoV infection were obtained according to the proteomics data from our previous study. The targets of baicalein-PDCoV interaction were obtained and analyzed by STRING database and Cytoscape 3.8.2 software to construct a network diagram of "baicalein-PDCoV-targets". The CytoNCA was used to analyze network topology and core network construction. Metascape database was used for GO and KEGG analysis of core network genes. The expression levels of genes in the predicted signaling pathways were detected in vitro. A total of 268 potential targets of baicalein were screened out. There were 75 potential targets of baicalein-PDCoV infection. GO enrichment results showed that baicalein was mainly involved in the formations of membrane raft, spindle and mitochondrial membrane, cell cycle and MAPK signaling pathways. A total of 277 signaling pathways (P < 0.01) were screened out by KEGG enrichment. The PI3K-Akt, Ras and MAPK signaling pathways were the main pathways that involved in the protective effects of baicalein against PDCoV infection. The results showed that compared with the cellular control groups, the mRNA expressions of PI3K, AKT and NF-B significantly increased in the PDCoV infection group. Compared with the PDCoV group, treatment of baicalein significantly decreased the mRNA expressions of PI3K, AKT and NF-B (P < 0.05). The effect of baicalein on PDCoV infection has the characteristics of multi-targets and multi-pathways, through the intervention of AKT1, HSP90AA1, SRC, EGFR, CASP3, MAPK, STAT3 and other core genes in regulating PI3K-Akt signaling pathway, Ras signaling pathway and MAPK signaling pathway, apoptosis, and virus infection. These results suggested that baicalein could be a potential therapeutic drug against PDCoV infection for further study.