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.

Prospects of lassa fever candidate vaccines

Background: Lassa fever is an acute viral haemorrhagic disease caused by the Lassa virus (LASV). It is endemic in West Africa and infects about 300,000 people each year, leading to approximately 5000 deaths annually. The development of the LASV vaccine has been listed as a priority by the World Health Organization since 2018. Considering the accelerated development and availability of vaccines against COVID-19, we set out to assess the prospects of LASV vaccines and the progress made so far. Materials and Methods: We reviewed the progress made on twenty-six vaccine candidates listed by Salami et al. (2019) and searched for new vaccine candidates through Google Scholar, PubMed, and DOAJ from June to July 2021. We searched the articles published in English using keywords that included "vaccine" AND "Lassa fever" OR "Lassa virus" in the title/. Results: Thirty-four candidate vaccines were identified - 26 already listed in the review by Salami et al. and an additional 8, which were developed over the last seven years. 30 vaccines are still in the pre-clinical stage while 4 of them are currently undergoing clinical trials. The most promising candidates in 2019 were vesicular stomatitis virus-vectored vaccine and live-attenuated MV/LASV vaccine;both had progressed to clinical trials. Conclusions: Despite the focus on COVID-19 vaccines since 2020, LASV vaccine is under development and continues to make impressive progress, hence more emphasis should be put into exploring further clinical studies related to the most promising types of vaccines identified.

Evaluation of expression and titration of recombinant nucleocapsid protein as an immunogenic candidate against SARS-CoV2

Introduction: Covid-19 epidemic results from an infection caused by SARS-CoV2. Evolution-based analyses on the nucleotide sequences show that SARS-CoV2 is a member of the genus Beta-coronaviruses and its genome consists of a single-stranded RNA, encoding 16 proteins. Among the structural proteins, the nucleocapsid is the most abundant protein in virus structure, highly immunogenic, with sequence conservatory. Due to a large number of mutations in the spike protein, the aim of this study was to investigate bioinformatics, expression of nucleocapsid protein and evaluate its immunogenicity as an immunogenic candidate. Materials and Methods: B and T cell epitopes of nucleocapsid protein were examined in the IEDB database. The PET28a-N plasmid was transferred to E. coli BL21(DE3) expression host, and IPTG induced recombinant protein expression. The protein was purified using Ni-NTA column affinity chromatography, and the Western blotting method was utilized to confirm it. Finally, mice were immunized with three routes of purified protein. Statistical analysis of the control group injection and test results was carried out by t-test from SPSS software. Results: The optimized gene had a Codon adaptation index (CAI) of 0/97 Percentage of codons having high- frequency distribution was improved to 85%. Expression of recombinant protein in E. coli led to the production of BoNT/B-HCC with a molecular weight of 45 kDa. The total yield of purified protein was 43 mg/L. Immunization of mice induced serum antibody response. Statistical analysis showed that the antibody titer ratio was significantly different compared to the control sample and the antibody titer was acceptable up to a dilution of 1.256000. Conclusion: According to the present study results, the protein can be used as an immunogenic candidate for developing vaccines against SARS-CoV2 in future research.

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.

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.

In-silico studies of active phytochemicals from siddha medicinal herbs of karisalai chooranam against SARS-CoV-2 main protease (3 CLpro), RNA dependent RNA polymerase and angiotensin-converting enzyme II receptor

Aim: The contagious disease COVID 19 is a recently out-broken pandemic situation which threatens humankind all over the world. Siddha system of medicine is one of the traditional medical systems of India, which has provided a novel remedy for many epidemics like Dengue, Chicken guinea earlier. On evaluating the literature evidence and considering the mortality and severity of the disease, we have attempted to identify the possible inhibition of viral replication by "Karisalai Chooranam" - a polyherbal Siddha formulation which contains herbs like Karisalai (Wedelia chinensis), Thoodhuvelai (Solanum trilobatum), Musumusukai (Melothria maderaspatana) and Seeragam (Cuminum cyminum). The aim of this study was to identify the bioactive components present in Karisalai chooranam and pin down the components that inhibit COVID 19 protease by In Silico molecular docking analysis. Material and methods: The study was performed for the active compounds present in the herbs (Wedelia chinensis - Benzoic acid, Solanum trilobatum- Disogenin, Melothria maderaspatana- beta-sitosterol, Cuminum cyminum L- Coumaric acid and Limonene) with three potential targets, PDB id: 6LU7 3-chymotrypsin-like protease (3CLpro), PDB id: 6-NUR RNA dependent RNA polymerase and PDB id: 2AJF Angiotensin-converting enzyme II (ACE2) receptor using Autodock Vina. Key findings: The active phytocomponents present in "Karisalai chooranam" was found to inhibit the target 3CL proenzyme and hereby halt the formation of 16 non-structural proteins (nsp1-nsp16) that are highly essential for viral replication and there by prevents viral survival in the host environment. The phytocomponents also inhibited the target RNA dependent RNA polymerase (PDB)-6NUR RdRp which possess versatile action in mediating nonstructural protein (nsp 12) essential for viral replication. A significant binding against the target Angiotensin-converting enzyme II (ACE2) receptors - PDB- 2AJF was found which was recognized as a binding site for novel coronavirus to cause its pathogenesis. Among the five active components present in the herb, the binding ability of Disogenin and beta-sitosterol with COVID19 protease suggests a possible mechanism of protease inhibition and thus preventing viral replication. Significance: The results strongly suggest that phytocomponents of "Karisalai chooranam" may act as a potential therapeutic agent for the management of COVID-19 and related symptoms. Further, the efficacy of the active compounds should be tested in vitro before being recommended as a drug.

Fructus aurantii extracts ameliorate intestinal inflammation and regulate the intestinal barrier through Fc epsilon RI signaling pathway

Fructus Aurantii (FA) is the dry and immature fruit of Citrus aurantium L. and its rutaceous cultivars. FA has been widely used to treat digestive system diseases since ancient China, and it promotes gastrointestinal (GI) motility in functional dyspepsia (FD), but its potential therapeutic mechanisms remain unclear. We examined the effects of FA ethanol extracts in an iodoacetamide (IA)-induced FD rat model. Firstly, key FA therapy targets for FD were gathered using systematic pharmacology. Combined with systemic pharmacological analyses, plasma metabolomics based on UPLC-QTOF-MS were conducted. Then, MetaboAnalyst was used to jointly analyze systemic pharmacology targets and metabolomic metabolites to select key metabolic pathways. Finally, the key path is verified by experiments. FA exerted distinct therapeutic effects in anti-inflammation and promoting gastrointestinal motility in our IA-induced FD rat model. When compared with the model group, FA down-regulated the inflammatory factors interleukin 1beta and tumor necrosis factor-a. At the same time, FA up-regulated tight junction proteins in the intestinal epithelial barrier. Through the integrated analysis of metabolomics and systemic pharmacology, we conducted experimental verification on Fc epsilon RI signaling pathway. When compared with the model group, FA down-regulatedphospho-mitogen activated protein kinase, phospho-extracellular signal regulated kinase1/2, myosin light chain kinase, and phospho-myosin regulatory light chain protein levels. Thus, FA ameliorated FD by regulating the Fc epsilon RI signaling pathway. Our integrated strategy identified underlying FA mechanisms toward FD treatment and provided a foundation for FA development as a clinical agent for FD.

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.

International Conference on "Biotechnological Interventions to Overcome Challenges of Covid/post-Covid Era-2022" (BIOCoPE-2022), Rajasthan, India, 24-25 March 2022

This journal issue includes 31 articles that discuss salt stress in plants and amelioration strategies;algal biorefinery;in-silico docking studies of selected phytochemicals against papain like protease of SARS-Cov-2;development of an effective strategy using green synthesized nanoparticles;effect of methyl jasmonate in enhanced growth, antioxidants and reduced Pb uptake in contrasting cluster bean cultivars;biosynthesis of silver nanoparticles using mushroom extract and its toxicity assessement in zebrafish embryos;phytogenic synthesis of metallic nanoparticles;abiotic stress responses and strategies of microbes mediated mitigation for sustainable agriculture.

The possibility of using perfluorocarbon compounds for virus-associated pneumonia treatment

The issues of practicality in using perfluorocarbon gas transport emulsions (or pure perfluorocarbons) in severe virus-associated pneumonia treatment were considered, including those caused by coronavirus infection. Perfluorocarbons are fully fluorinated carbon compounds, on the basis of which artificial blood substitutes have been developed - gas transport perfluorocarbon emulsions for medical purposes. Perfluorocarbon emulsions were widely used in the treatment of patients in critical conditions of various genesis at the end of the last-the beginning of this century, accompanied by hypoxia, disorders of rheological properties and microcirculation of blood, perfusion of organs and tissues, intoxication, and inflammation. Large-scale clinical trials have shown a domestic plasma substitute advantage based on perfluorocarbons (perfluoroan) over foreign analogues. It is quite obvious that the inclusion of perfluorocarbon emulsions in the treatment regimens of severe virus-associated pneumonia can significantly improve this category's treatment results after analyzing the accumulated experience. A potentially useful area of therapy for acute respiratory distress syndrome is partial fluid ventilation with the use of perfluorocarbons as respiratory fluids as shown in the result of many studies on animal models and existing clinical experience. There is no gas-liquid boundary in the alveoli, as a result of which, there is an improvement in gas exchange in the lungs and a decrease in pressure in the respiratory tract when using this technique, due to the unique physicochemical properties of liquid perfluorocarbons. A promising strategy for improving liquid ventilation effectiveness using perfluorocarbon compounds is a combination with other therapeutic methods, particularly with moderate hypothermia. Antibiotics, anesthetics, vasoactive substances, or exogenous surfactant can be delivered to the lungs during liquid ventilation with perfluorocarbons, including to the affected areas, which will enhance the drugs accumulation in the lung tissues and minimize their systemic effects. However, the indications and the optimal technique for conducting liquid ventilation of the lungs in patients with acute respiratory distress syndrome have not been determined currently. Further research is needed to clarify the indications, select devices, and determine the optimal dosage regimens for perfluorocarbons, as well as search for new technical solutions for this technique.

Susceptibility of different animal species to experimental infection with SARS-CoV-2 (review)

The susceptibility of animal species to SARS-CoV-2, under experimental conditions, is a subject of great interest for the international scientific community. Compared to observational studies of natural disease outbreaks in different animal species, experimental studies based on in silico, in vitro and in vivo research, are important alternatives to evaluate the prediction of potential hosts for SARS-CoV-2 infection. In order to determine the susceptibility of a host species and the risk of acting as a potential animal reservoir, a large number of different animal species, domestic and wild, were experimentally infected with SARS-CoV-2, which were classified as permissive or resistant. Experimental infections have proven to be crucial for clarifying aspects of the pathogenetic mechanism, viral persistence and elimination, immune response, antiviral sensitivity, vaccine production, immunotherapy and improving diagnostic methods. In this article, some experimental infections carried out in different animal species will be reviewed, according to the data from the literature.

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.

Network pharmacological mechanism of Runfei Ningshen Decoction in the treatment of insomnia caused by COVID-19

Objective: To study the mechanism of Runfei Ningshen Decoction in the treatment of insomnia caused by corona virus disease 2019(COVID-19) by using network pharmacology and molecular docking analysis. Methods: The chemical components and targets of Chinese medicinal materials of Runfei Ningshen Decoction in TCMSP, Batman, and CTD databases were searched. The relevant targets of novel coronavirus pneumonia and insomnia in Disgenet, GeneCards, CTD, and Malacards databases were searched. The component-target-disease network was established by using Cytoscape 3.2.1 software;The protein-protein intereation(PPI) network was constructed in string database. The common targets were enriched by using Cluster Profiler software package in R language software platform. The molecular docking of core targets related to insomnia caused by COVID-19 was carried out by using Discovery Studio 4.0 software. Results: 349 medicinal ingredients in Runfei Ningshen Decoction, 1 904 targets, 1 505 new coronavirus pneumonia-related targets, and 1 337 insomnia-related targets were collected. When the intersection of Venn diagrams were used, 404 common targets were obtained for the 2 diseases. 250 targets were intersected with the 2 diseases, and 33 core targets were screened out by the analysis of the interaction network between targets. Pathway enrichment analysis showed that Runfei Ningshen Decoction mainly acts on AKT1, INS, TP53, IL-6, key targets such as AKT1, INS, TP53, IL-6, JUN, CASP3, TNF, CAT, PTGS2 and CXCL8, which are involved in the important pathway processes such as human cytomegalovirus infection, fluid shear stress, and AGE-RAGE signaling pathways in complications of atherosclerosis and diabetes. The results of molecular docking showed that the core target has a high affinity with beta-sitosterol, 1-methoxy phaseolin, 3'-hydroxy-4'-O-methylglycyrrhizin, and anhydroicariin. The prescription treatment of insomnia caused by COVID-19 may be through the targets such as PTGS2, AR, PPARG, NOS2, HSP90 AA1 and so on. Conclusion: Runfei Ningshen Decoction can treat insomnia caused by COVID-19 by inhibiting IL-6 and TNF-a.

A study of antioxidant and physicochemical stability in antipyretic decoction of traditional Lanna recipe

During the current COVID-19 outbreak, Thai traditional antipyretic recipes and antipyretic herbs have been widely studied. Antipyretic Thai/Lanna herbal decoction for relieving fever in the North consists of Tinospora crispa, Rhinacanthus nasutus, Sauropus androgynus and Alstonia scholaris. This research aimed to study the physical stability, pH, sedimentation, and color of the Lanna antipyretic decoction at 4 degrees C 25 degrees C and 40 degrees C with 75 +or- 5% RH for 7 days. The testing included the Folin Ciocalteu method for quantifying total phenolic content, the aluminium chloride colorimetry for flavonoid content, and the DPPH radical scavenging and ABTS methods for antioxidant activities. The results demonstrated that, for the decoction, the pH values at various temperatures dropped with storage time, the sediment amounts increased with storage time, but its color did not change at 4 degrees C. Its total phenolic and flavonoid contents rose with storage time. The total phenolic contents in mg GAE/g extract at Days 0 and 7 were 161.13 +or- 5.62 and 15.34 +or- 6.21 at 4 degrees C, 160.53 +or- 11.78 and 14.32 +or- 1.13 at 25 degrees C, and 160.09 +or- 7.39 and 12.82 +or- 6.91 at 40 degrees C, respectively;while the flavonoid contents in mgQE/g extract at Days 0 and 7 were 20.32 +or- 0.43 and 7.80 +or- 0.34 at 4 degrees C, 20.10 +or- 0.47 and 7.27 +or- 0.20 at 25 degrees C, and 20.06 +or- 0.55 and 6.63 +or- 0.43 at 40 degrees C, respectively. The decoction's free radical inhibition (IC50) values at 4 degrees C, 25 degrees C and 40 degrees C by DPPH ranged from 14.74 +or- 0.04 to 23.18 +or- 0.72%w/w;and by ABTS the values ranged from 2.63 +or- 0.12 to 3.95 +or- 0.05%w/w. At the storage temperature of 4 degrees C, the decoction showed the best physical stability. Thus, the results can be used in setting up storage guidelines for Thai traditional and folk decoctions to ensue the best stability.

Kadsura japonica fruits exert immunostimulatory and anti-obesity activity in RAW264.7 and 3T3-L1 cells

Under the COVID-19 pandemic, interest in immune enhancement and anti-obesity is increasing. Thus, in this study, we investigated whether Kadsura japonica fruits (KJF) exhibits immunostimulatory activity and anti-obesity activity. KJF increased the production of immunostimulatory factors and phagocytosis in RAW264.7 cells. Inhibition of TLR2 and TLR4 blocked KJF-mediated production of immunostimulatory factors in RAW264.7 cells. In addition, the inhibition of MAPK and PI3 K/AKT signaling pathway reduced KJF-mediated production of immunostimulatory factors, and the activation of MAPK and PI3 K/AKT signaling pathway by KJF suppressed the inhibition of TLR2/4. KJF attenuated the lipid accumulation and the protein expression such as CEBPa, PPARP, perilipin-1, adiponectin, and FABP4 related to the lipid accumulation in 3T3-L1 cells. In addition, KJF inhibited excessive proliferation of 3T3-L1 cells and protein expressions such as beta-catenin and cyclin D1 related to cell growth. These findings indicate that KJF may have immunostimulatory activity and anti-obesity activity.

Do uncommon plant phenolic compounds have uncommon properties? A mini review on novel flavonoids

Unique plants and their properties, once considered synonymous to medicine, remain a potent source for new compounds in modern science. Plant polyphenols and natural products continue to be investigated for effective treatments for the most persistent of human ailments. In this review, fifty novel plant phenolic compounds have been compiled and briefly described from the previous five years. Select compounds and notable plant species from genus Morinda and Sophora are further expanded on. Traditional medicine plants often contain rich and diverse mixtures of flavonoids, from which rare compounds should receive attention. The bioactivity of crude plant extracts, purified compounds and mixtures can differ greatly, requiring that these interactions and mechanisms of action be investigated in greater detail. Novel applications of uncommon natural products, namely mimosine and juglone, are explored within this review. The 2019 coronavirus pandemic has resulted in abrupt spike of related scientific publications: speculation is made regarding plant natural products and future of antiviral drug discovery.

In silico-based studies on phytochemicals from native Indian plants as potential inhibitors of SARS-CoV-2

This study aims to analyze the AntiCovid effect of Phytocompounds extracted from Native Indian Plant species by computational methods such as Molecular Docking. Through this study keeping the Indian Heritage alive we characterized the ability of these phytochemicals as inhibiting agents of the Main Protease enzyme of this Virus. The lack of any effective treatment and the reoccurrence of cases despite Vaccination necessitates the quick provision of anti-SARS-CoV-2 drugs. Natural substances are getting a lot of attention for SARS-CoV-2 therapy as they have proven antimicrobial activities and are a key source for numerous antiviral drugs. Despite the fact that this virus has several identified target receptors, Main Protease (Mpro) is crucial for viral replication. In this study, 26 phytochemicals from 10 native Indian plant species were studied. Our docking studies demonstrated that compounds Quercetin, Withaferin A, Sominone, and Nimbin were likely to be more favorable than the natural inhibitor N3, with binding energies of-8.42, -9.21, -9.95, and -8.88 kcal/mol, respectively. These four candidate natural compounds were further examined for their bioavailability scores through ADMET analysis to prove the safety of these compounds as well as their drug likeliness. Through the results it was indicated that these natural phytochemicals have a significant potential of inhibiting the SARS-CoV-2 Mpro enzyme and might be utilized to treat SARS-CoV-2 and manage public health, subject to in vitro validation in the future.

Study in-silico oleanane triterpenoids in Aquilaria spp. as a COVID-19 antiviral

Covid-19, a disease characterized by Severe Acute Respiratory Syndrome, is caused by Coronavirus-2 (SARS-CoV-2). This virus causes tissue damage and a decrease in the respiratory system. Agarwood (Aquilaria spp) is a plant that has various pharmacological activities, including relieving respiratory diseases. One of the several secondary metabolites reported in Aquilaria spp. is oleanane triterpenoids, suspected of having antiviral activity. This research was aimed to determine the potential of oleanane triterpenoids from Agarwood as a covid-19 antiviral by in silico study. The research methods were molecular docking, prediction of Lipinski rules of five, and prediction of ADME. As a receptor, main protease (Mpro) Covid-19 was used. The four oleanane triterpenoid compounds in Agarwood demonstrated a higher affinity for the main protease covid-19 (G 11-oxo-beta-amyrin = -9.8 kcal/mol, G hederagenin-an = -9.6 kcal/mol, G 3beta-acetoxyfriedelane = -9.4 kcal/mol, G ursolic acid = -9.5 kcal/mol) than Lopinavir (G = -6.2 kcal/mol) and Remdesivir (G = -7.2 kcal/mol). The major amino acids involved in ligand and receptor interactions are methionine 49 and 165, proline 168, glutamine 189, arginine 188, and threonine 25. According to the prediction of Lipinski's rule of five and ADME, hederageninan is potential for development as oral medicine.

Study on the effect of Xuanfei Jiere Granules in the treatment of COVID-19 by network pharmacology and molecular docking

Objective: To explore the effect and mechanism of Xuanfei Jiere Granules in the treatment of corona virus disease 2019 (COVID-19) complicated with fever. Methods: The effective components of Xuanfei Jiere Granules were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the potential target genes were predicted. The disease targets of COVID-19 complicated with fever were searched by GeneCards and CTD databases, and the common targets were obtained, and then introduced into Cytoscape to construct the "component-target-disease" network. The above 2 common targets were input into the online database of STRING protein interaction, and the results were imported into Cytoscape software to obtain Protein-Protein Interaction(PPI) network;R language was used to analyze the common targets with Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis. Results: 84 active components and 82 targets were obtained. The pathway enrichment analysis showed that Xuanfei Jiere Granules mainly acted on protein kinase B(AKT1), tumor protein P53(TP53), interleukin-6(IL6) and other key targets in the treatment of COVID-19 complicated with fever. KEGG pathway enrichment analysis showed that the action was mainly related to the influence of fluid shear stress and atherosclerosis, human cytomegalovirus infection, and AGE-RAGE in diabetic complications and other signal pathways. The results of molecular docking showed that the core target had strong affinity with beta-sitosterol, formononetin, N-trans ferulyl tyramine and so on. Conclusion: This study preliminarily verified that Xuanfei Jiere Granules can play a role in the treatment of COVID-19 complicated with fever through multi-components, multi-targets and multi-pathways.