Inhibition of SARS-CoV2 Replication Regulated by NSP3 through Ayurveda Phytoconstituents of Indian Traditional Medicine

With Covid-19, a significant proportion of the population who are already vaccinated have tested positive. Therefore, there is a need for better medicines that act against the virus rigorously without causing any side effects. We aim to achieve the same through molecular docking and further simulations for bioactive phytochemicals of ayurvedic medicinal plants. The target for this study has been considered the NSP3 protein of the viral RNA that actively takes part in both replication and immune evasion pathways of the virus. Ligand libraries consisting of bioactive phytochemicals of aswasgandha and analogues of curcumin and piperine are curated. The libraries, along with the NSP3 protein moiety are docked onto two active sites. With the best-scored complexes further taken up for molecular dynamics simulation, the study resulted in favourable outcomes for three such ligands (compound ID 5469426, 69501714, ZINC000003874317). © 2023 Bharati Vidyapeeth, New Delhi.

An integrated computational approach towards the screening of active plant metabolites as potential inhibitors of SARS-CoV-2: an overview.

COVID-19 and its causative organism SARS-CoV-2 paralyzed the world and was designated a pandemic by the World Health Organization in March 2020. The worldwide health system is trying to discover an effective therapeutic measure since no clinically authorized medications are present. Screening of plant-derived pharmaceuticals may be a viable technique to fight COVID-19 in this vital situation. This review discusses the potential application of in silico approaches in developing new therapeutic molecules related to preventing SARS-CoV-2 infection. Also, it describes the binding affinity of various phytoconstituents with distinct SARS-CoV-2 target sites. In this perspective, an extensive literature survey was carried out to find the potential phytoconstituents to develop new therapeutic entities to treat COVID-19 in different online academic databases and books. Data retrieved from databases were analyzed and interpreted to conclude that many phytochemicals will bind with the 3-chymotrypsin-like (3CLpro) and papain-like proteases (PLpro), spike glycoprotein, ACE-2, NSP15-endoribonuclease, and E protein targets of SARS-CoV-2 main protease using in silico molecular docking approach. The present investigations reveal that phytoconstituents such as curcumin, apigenin, chrysophanol, and gingerol are significantly binding with spike glycoprotein; laurolistine, acetoside, etc. are bound with Mpro for anti-SARS-CoV-2 therapies. Using virtual applications of in silico studies, the current study constitutes a progressive data analysis on the mechanism of binding efficiency of distinct classes of plant metabolites against the active sites of SARS-CoV-2. Furthermore, the current review also demonstrates the fundamental necessity of the alternative and complementary medicine for future therapeutic uses of phytoconstituents by phytochemists in the fight against COVID-19.

Investigation of Neolamarckia cadamba Phytoconstituents Against SARS-CoV-2 3CL Pro: An In-Silico Approach

In present study, the inhibitory potential of Neolamarckia cadamba phytoconstituents was investigated against SARS-CoV-2 3CL protease (3CL pro) (PDB ID: 6M2N). Molecular docking was analyzed using AutoDock Vina software by setting the grid parameter as X=-33.163, Y=-65.074 and Z= 41.434 with dimensions of the grid box 25 × 25 × 25 Å. Remdesivir was taken as the standard for comparative analysis along with inhibitor 5, 6, 7-trihydroxy-2-phenyl-4H-chromen-4-one. Furthermore, the exploration of 2 D Hydrogen-bond interactions was performed by Biovia Discovery Studio 4.5 program to identify the interactions between an amino acid of target and ligand followed by assessment of physicochemical properties using Lipinski's rule and Swiss ADME database. The decent bonding scores of secondary metabolites owing to hydrogen bonding with catalytic residues suggest the effectiveness of these phytochemicals towards 3CLpro. The results are further consolidated positively by Lipinski's rule and Swiss ADME prediction. Thus reasonably, observations with docking studies suggest possibility of phytochemicals from Neolamarckia cadamba to inhibit the 3CLpro and consequently would be explored further as agents for preventing COVID-19. © 2023, Universidade Federal de Mato Grosso do Sul, Departamento de Quimica. All rights reserved.

An In-silico Multi-Targeted Approach in Search of Potential Drug Candi-date(s) Against SARS-CoV-2 Lung Infection

Background: The multitargeted computational approach for the design of drugs to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lung infection from herbal sources may lead to compound(s) that is/are safe (derived from natural sources), effective (act on predefined targets) and broad spectrum (active in both, adult and juvenile population). Objective(s): The present work aims at developing a specific and effective treatment for a lung infection in both the adult and juvenile population, caused due to SARS-CoV-2 through a computational approach. Method(s): A systematic virtual screening of 27 phytoconstituents from 11 Indian herbs with antiviral, anti-inflammatory, and immunomodulatory activity was performed. After applying the Lipinski rule of five, 19 compounds that fitted well were subjected to molecular docking studies using Molegro virtual docker 6.0 with two targets viz. SARS-CoV-2 main protease (Mpro) (PDB ID 6LU7) and ACE receptor (PDB ID 6M0J). The best-docked complexes were used to develop a merged feature pharmacophore using Lig-andscout software, to know the structural requirements to develop multitarget inhibitor(s) of SARS-CoV-2. Drug likeliness and ADMET studies were also performed. Result(s): The results revealed that Syringin, a glycoside from Tinospora cordifolia, has a good binding affinity towards both targets as compared to Remdesivir. Furthermore, drug likeliness and ADMET studies established its better bioavailability and low toxicity. Conclusion(s): The pharmacophores developed from protein-ligand complexes provided an important understanding to design multitarget inhibitor(s) of SARS-CoV-2 to treat COVID-19 lung infection in both the adult and juvenile populations. Syringin may be subjected to further wet-lab studies to establish the results obtained through in-silico studies.Copyright © 2022 Bentham Science Publishers.

Screening for Potential Traditional Herbal Inhibitors Against 3-Chymo-trypsin-like Main Protease (3CLpro) from Four Different Coronaviruses: An in silico Approach

Background: The recent outbreak of the COVID-19 pandemic has raised a global health concern due to the unavailability of any vaccines or drugs. The repurposing of traditional herbs with broad-spectrum anti-viral activity can be explored to control or prevent a pandemic. Objective(s): The 3-chymotrypsin-like main protease (3CLpro), also referred to as the "Achilles' heel" of the coronaviruses (CoVs), is highly conserved among CoVs and is a potential drug target. 3CLpro is essential for the virus' life cycle. The objective of the study was to screen and identify broad--spectrum natural phytoconstituents against the conserved active site and substrate-binding site of 3CLpro of HCoVs. Method(s): Herein, we applied the computational strategy based on molecular docking to identify potential phytoconstituents for the non-covalent inhibition of the main protease 3CLpro from four different CoVs, namely, SARS-CoV-2, SARS-CoV, HCoV-HKU1, and HCoV-229E. Result(s): Our study shows that natural phytoconstituents in Triphala (a blend of Emblica officinalis fruit, Terminalia bellerica fruit, and Terminalia chebula fruit), namely chebulagic acid, chebulinic acid, and elagic acid, exhibited the highest binding affinity and lowest dissociation constants (Ki), against the conserved 3CLpro main protease of SARSCoV-2, SARS-CoV, HCoV-HKU1, and HCoV-229E. Besides, phytoconstituents of other herbs like Withania somnifera, Glycyrrhiza glabra, Hyssopus officinalis, Camellia sinensis, Prunella vulgaris, and Ocimum sanctum also showed good binding affinity and lower Ki against the active site of 3CLpro. The top-ranking phyto-constituents' binding interactions clearly showed strong and stable interactions with amino acid residues in the catalytic dyad (CYS-HIS) and substrate-binding pocket of the 3CLpro main proteases. Conclusion(s): This study provides a valuable scaffold for repurposing traditional herbs with anti--CoV activity to combat SARS-CoV-2 and other HCoVs until the discovery of new therapies.Copyright © 2021 Bentham Science Publishers.

Inhibitory Potentials of Phytoconstituents of Phyllanthus amarus against Severe Acute Respiratory Syndrome-Corona Virus-2 Main Protease: A Computational Aided Approach

In 2019, a new strain of Coronavirus disease was identified in Wuhan, China. Specific therapies are unavailable and investigations regarding Coronavirus disease treatment are lacking. The present study aimed to assess bioactive compounds found in medicinal plant Phyllanthus amarus as potential Coronavirus disease main protease inhibitors, using a molecular docking study. Molecular docking was performed using Autodock 4.2. Coronavirus disease main protease was docked with several compounds, and docking was analysed by Autodock 4.2, Lopinavir was used as standard for comparison. The binding energies obtained from the docking of 6LU7 with native ligand, lopinavir, Phyllanthin, Hypophyllanthin, Hexanedioic acid, bis (2-ethylhexyl) ester, Benzeneethanamine,3,4-dimethoxy-n-((pentafluoro phenyl) methylene), Phenethylamine, 2-methoxy-alpha.-methyl-4,5-(methylenedioxy), Diisooctyl adipate, P-Tert-Octylresorcinol, 4-methyl-2,5-dimethoxy phenethylamine, 3-(2,4-dimethoxy-phenyl)-2-formylamino-propionic acid, ethyl ester, Rutin, Quercetin and Niranthin were-6.08,-4.44,-4.14,-2.32,-4.23,-4.07,-2.5,-4.66,-4.14,-3.38,-7.46,-6.28 and-4.62 kcal/mol, respectively. Therefore, lopinavir may represent potential treatment option and Rutin and Quercetin appeared to have the best potential to act as Coronavirus disease main protease inhibitors. Thus all the compounds have shown significant binding energy and potent inhibitory effect against Coronavirus disease main protease. However, further research is necessary to investigate their potential medicinal use.

Butein as a potential binder of human ACE2 receptor for interfering with SARS-CoV-2 entry: a computer-aided analysis.

Natural products have been included in our dietary supplements and have been shown to have numerous therapeutic properties. With the looming danger of many zoonotic agents and novel emerging pathogens mainly of viral origin, many researchers are launching various clinical trials, testing these compounds for their antiviral activity. The present work deals with some of the available natural compounds from the literature that have demonstrated activity in counteracting pathogen infections. Accordingly, we screened, using in silico methods, this subset of natural compounds for searching potential drug candidates able to interfere in the recognition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and its target human angiotensin-converting enzyme 2 (hACE2) receptor, leading to the viral entry. Disrupting that recognition is crucial for slowing down the entrance of viral particles into host cells. The selected group of natural products was examined, and their interaction profiles against the host cell target protein ACE2 were studied at the atomic level. Based on different computer-based procedures including molecular docking, physicochemical property evaluation, and molecular dynamics, butein was identified as a potential hit molecule able to bind the hACE2 receptor. The results indicate that herbal compounds can be effective for providing possible therapeutics for treating and managing coronavirus disease 2019 (COVID-19) infection.

Uncovering of Anti-dengue Molecules from Plants Prescribed for Dengue: A Computational Investigation

Dengue fever is a tropical disease spread worldwide, transmitted by the mosquito Aedes aegypti. It affects 100 million people worldwide every year and half a million cases of dengue hemorrhagic fever are registered. At present, it poses sever health burden as combined infections of COVID-19. Currently, as a combined infection with COVID-19, it is becoming a serious health burden. To identify the active molecule, Maestro V12.7 was used with different tools including LigPrep, Grid Generation, SiteMap, Glide XP Docking, Pharmachophores and MM-GBSA. The UNRESS tool was also used to assess the protein stability with this dengue protein. The docking result showed that all examined phytocomponents except berberine and -(+)-l-alliin had good docking scores of -8.577 (azadirachtin), -8.112 (curcumin), -7.348 (apigenin) and -6.028 (andrographolide). However, berberine and -(+)-l-alliin possessed good hydrogen-bonding interactions with RdRp. In addition, molecular dynamic simulations demonstrate that the complex of azadirachtin and dengue protein has a solid understanding of the precise interactions. As per the research results, the present research suggests that this is the first statement of azadirachtin against NS5 RNA-dependent RNA polymerase domain (RdRp), despite extensive research on this molecule in previous investigations. Furthermore, we anticipate that molecules such as curcumin, apigenin, and andrographolide would show beneficial effects while in vitro and in vivo studies are conducted on virally related objects. Since we performed ADMET and pharmacokinetic properties in this research, we feel that the phytochemicals of the screened anti-dengue molecules may not need to be evaluated for toxicological effects.

Interaction of Bioactive Compounds of Moringa oleifera Leaves with SARS-CoV-2 Proteins to Combat COVID-19 Pathogenesis: a Phytochemical and In Silico Analysis.

Novel SARS-CoV-2 claimed a large number of human lives. The main proteins for viral entry into host cells are SARS-CoV-2 spike glycoprotein (PDB ID: 6VYB) and spike receptor-binding domain bound with ACE2 (spike RBD-ACE2; PDB ID: 6M0J). Currently, specific therapies are lacking globally. This study was designed to investigate the bioactive components from Moringa oleifera leaf (MOL) extract by gas chromatography-mass spectroscopy (GC-MS) and their binding interactions with spike glycoprotein and spike RBD-ACE2 protein through computational analysis. GC-MS-based analysis unveiled the presence of thirty-seven bioactive components in MOL extract, viz. polyphenols, fatty acids, terpenes/triterpenes, phytosterols/steroids, and aliphatic hydrocarbons. These bioactive phytoconstituents showed potential binding with SARS-CoV-2 spike glycoprotein and spike RBD-ACE2 protein through the AutoDock 4.2 tool. Further by using AutoDock 4.2 and AutoDock Vina, the top sixteen hits (binding energy ≥ - 6.0 kcal/mol) were selected, and these might be considered as active biomolecules. Moreover, molecular dynamics simulation was determined by the Desmond module. Interestingly two biomolecules, namely ß-tocopherol with spike glycoprotein and ß-sitosterol with spike RBD-ACE2, displayed the best interacting complexes and low deviations during 100-ns simulation, implying their strong stability and compactness. Remarkably, both ß-tocopherol and ß-sitosterol also showed the drug- likeness with no predicted toxicity. In conclusion, these findings suggested that both compounds ß-tocopherol and ß-sitosterol may be developed as anti-SARS-CoV-2 drugs. The current findings of in silico approach need to be optimized using in vitro and clinical studies to prove the effectiveness of phytomolecules against SARS-CoV-2.

Ethnobotanical Uses, Phytochemistry, Toxicology, and Pharmacological Properties of Euphorbia neriifolia Linn. against Infectious Diseases: A Comprehensive Review.

Medicinal plants have considerable potential as antimicrobial agents due to the presence of secondary metabolites. This comprehensive overview aims to summarize the classification, morphology, and ethnobotanical uses of Euphorbia neriifolia L. and its derived phytochemicals with the recent updates on the pharmacological properties against emerging infectious diseases, mainly focusing on bacterial, viral, fungal, and parasitic infections. The data were collected from electronic databases, including Google Scholar, PubMed, Semantic Scholar, ScienceDirect, and SpringerLink by utilizing several keywords like 'Euphorbia neriifolia', 'phytoconstituents', 'traditional uses', 'ethnopharmacological uses', 'infectious diseases', 'molecular mechanisms', 'COVID-19', 'bacterial infection', 'viral infection', etc. The results related to the antimicrobial actions of these plant extracts and their derived phytochemicals were carefully reviewed and summarized. Euphol, monohydroxy triterpene, nerifoliol, taraxerol, ß-amyrin, glut-5-(10)-en-1-one, neriifolione, and cycloartenol are the leading secondary metabolites reported in phytochemical investigations. These chemicals have been shown to possess a wide spectrum of biological functions. Different extracts of E. neriifolia exerted antimicrobial activities against various pathogens to different extents. Moreover, major phytoconstituents present in this plant, such as quercetin, rutin, friedelin, taraxerol, epitaraxerol, taraxeryl acetate, 3ß-friedelanol, 3ß-acetoxy friedelane, 3ß-simiarenol, afzelin, 24-methylene cycloarenol, ingenol triacetate, and ß-amyrin, showed significant antimicrobial activities against various pathogens that are responsible for emerging infectious diseases. This plant and the phytoconstituents, such as flavonoids, monoterpenoids, diterpenoids, triterpenoids, and alkaloids, have been found to have significant antimicrobial properties. The current evidence suggests that they might be used as leads in the development of more effective drugs to treat emerging infectious diseases, including the 2019 coronavirus disease (COVID-19).

Insights into the Antimicrobial, Antioxidant, Anti-SARS-CoV-2 and Cytotoxic Activities of Pistacia lentiscus Bark and Phytochemical Profile; In Silico and In Vitro Study.

Foodborne infections and antibiotic resistance pose a serious threat to public health and must be addressed urgently. Pistacia lentiscus is a wild-growing shrub and has been utilized for medicinal applications as well as for culinary purposes. The antibacterial and antioxidant activities of P. lentiscus bark in vitro, as well as the phytochemical composition, are the focus of this inquiry. The bark extract of P. lentiscus showed significant antimicrobial activity in experiments on bacteria and yeast isolated from human and food sources. The exposure time for the complete inhibition of cell viability of P. aeruginosa in the extracts was found to be 5% at 15 min. Phytochemical inquiry of the methanol extract demonstrates the existence of carbohydrates, flavonoids, tannins, coumarins, triterpenes, and alkaloids. Deep phytochemical exploration led to the identification of methyl gallate, gallic acid, kaempferol, quercetin, kaempferol 3-O-α-rhamnoside, kaempferol 3-O-ß-glucoside, and Quercetin-3-O-ß-glucoside. When tested using the DPPH assay, the methanol extracts of P. lentiscus bark demonstrated a high free radical scavenging efficiency. Further, we have performed a molecular modelling study which revealed that the extract of P. lentiscus bark could be a beneficial source for novel flavonoid glycosides inhibitors against SARS-CoV-2 infection. Taken together, this study highlights the Pistacia lentiscus bark methanol extract as a promising antimicrobial and antiviral agent.

Olive Leaves as a Potential Phytotherapy in the Treatment of COVID-19 Disease; A Mini-Review.

Beginning from December 2019, widespread COVID-19 has caused huge financial misfortunes and exceptional wellbeing emergencies across the globe. Discovering an effective and safe drug candidate for the treatment of COVID-19 and its associated symptoms became an urgent global demand, especially due to restricted information that has been discharged with respect to vaccine efficacy and safety in humans. Reviewing the recent research, olive leaves were selected as a potential co-therapy supplement for the treatment and improvement of clinical manifestations in COVID-19 patients. Olive leaves were reported to be rich in phenolic compounds such as oleuropein, hydroxytyrosol, verbascoside, apigenin-7-O-glucoside, and luteolin-7-O-glucoside and also triterpenoids such as maslinic, ursolic, and oleanolic acids that have been reported as anti-SARS-CoV-2 metabolites in recent computational and in vitro studies. In addition, olive leaf extract was previously reported in several in vivo studies for its anti-inflammatory, analgesic, antipyretic, immunomodulatory, and antithrombotic activities which are of great benefit in the control of associated inflammatory cytokine storm and disseminated intravascular coagulation in COVID-19 patients. In conclusion, the described biological activities of olive leaves alongside their biosafety, availability, and low price make them a potential candidate drug or supplement to control COVID-19 infection and are recommended for clinical investigation.

Bioactive Based Nanocarriers for the Treatment of Viral Infections and SARS-CoV-2.

Since ancient times, plants have been used for their medicinal properties. They provide us with many phytomolecules, which serve a synergistic function for human well-being. Along with anti-microbial, plants also possess anti-viral activities. In Western nations, about 50% of medicines were extracted from plants or their constituents. The spread and pandemic of viral diseases are becoming a major threat to public health and a burden on the financial prosperity of communities worldwide. In recent years, SARS-CoV-2 has made a dramatic lifestyle change. This has promoted scientists not to use synthetic anti-virals, such as protease inhibitors, nucleic acid analogs, and other anti-virals, but to study less toxic anti-viral phytomolecules. An emerging approach includes searching for eco-friendly therapeutic molecules to develop phytopharmaceuticals. This article briefly discusses numerous bioactive molecules that possess anti-viral properties, their mode of action, and possible applications in treating viral diseases, with a special focus on coronavirus and various nano-formulations used as a carrier for the delivery of phytoconstituents for improved bioavailability.

Implication of in silico studies in the search for novel inhibitors against SARS-CoV-2.

Corona Virus Disease-19 (COVID-19) is a pandemic disease mainly caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It had spread from Wuhan, China, in late 2019 and spread over 222 countries and territories all over the world. Earlier, at the very beginning of COVID-19 infection, there were no approved medicines or vaccines for combating this disease, which adversely affected a lot of individuals worldwide. Although frequent mutation leads to the generation of more deadly variants of SARS-CoV-2, researchers have developed several highly effective vaccines that were approved for emergency use by the World Health Organization (WHO), such as mRNA-1273 by Moderna, BNT162b2 by Pfizer/BioNTech, Ad26.COV2.S by Janssen, AZD1222 by Oxford/AstraZeneca, Covishield by the Serum Institute of India, BBIBP-CorV by Sinopharm, coronaVac by Sinovac, and Covaxin by Bharat Biotech, and the first US Food and Drug Administration-approved antiviral drug Veklury (remdesivir) for the treatment of COVID-19. Several waves of COVID-19 have already occurred worldwide, and good-quality vaccines and medicines should be available for ongoing as well as upcoming waves of the pandemic. Therefore, in silico studies have become an excellent tool for identifying possible ligands that could lead to the development of safer medicines or vaccines. Various phytoconstituents from plants and herbs with antiviral properties are studied further to obtain inhibitors of SARS-CoV-2. In silico screening of various molecular databases like PubChem, ZINC, Asinex Biol-Design Library, and so on has been performed extensively for finding effective ligands against targets. Herein, in silico studies carried out by various researchers are summarized so that one can easily find the best molecule for further in vitro and in vivo studies.

Phytoconstituents from Moringa oleifera fruits target ACE2 and open spike glycoprotein to combat SARS-CoV-2: An integrative phytochemical and computational approach.

Therapeutic drugs based on natural products for the treatment of SARS-CoV-2 are currently unavailable. This study was conducted to develop an anti-SARS-CoV-2 herbal medicine to face the urgent need for COVID-19 treatment. The bioactive components from ethanolic extract of Moringa oleifera fruits (MOFs) were determined by gas chromatography-mass spectroscopy (GC-MS). Molecular-docking analyses elucidated the binding effects of identified phytocomponents against SARS-CoV-2 spike glycoprotein (PDB ID: 6VYB) and human ACE2 receptor (PDB ID: 1R42) through the Glide module of Maestro software. GC-MS analysis unveiled the presence of 33 phytocomponents. Eighteen phytocomponents exhibited good binding affinity toward ACE2 receptor, and thirteen phytocomponents had a high affinity with spike glycoprotein. This finding suggests that the top 11 hits (Docking score ≥ -3.0 kcal/mol) could inhibit SARS-CoV-2 propagation. Intriguingly, most of the phytoconstituents displayed drug-likeness with no predicted toxicity. However, further studies are needed to validate their effects and mechanisms of action. PRACTICAL APPLICATIONS: Moringa oleifera (MO) also called "drumstick tree" has been used as an alternative food source to combat malnutrition and may act as an immune booster. GC-MS analysis unveiled that ethanolic extract of Moringa oleifera fruits (MOFs) possessed 33 active components of pyridine, aromatic fatty acid, oleic acid, tocopherol, methyl ester, diterpene alcohol, triterpene and fatty acid ester and their derivatives, which have various pharmacological and medicinal values. Virtual screening study of phytocomponents of MOF with human ACE2 receptor and SARS-CoV-2 spike glycoprotein exhibited good binding affinity. Based on molecular docking, the top 11 hits (Docking score ≥-3.0 kcal/mol) might serve as potential lead molecules in antiviral drug development. Intriguingly, most of the phytoconstituents displayed drug-likeness with no predicted toxicity. Thus, MOF might be used as a valuable source for antiviral drug development to combat COVID-19, an ongoing pandemic.

Revisiting liquorice (Glycyrrhiza glabra L.) as anti-inflammatory, antivirals and immunomodulators: Potential pharmacological applications with mechanistic insight.

Background: Glycyrrhiza glabra L. (G. glabra) commonly known as liquorice is one of the highly exploited and utilized medicinal plant of the world. Since ancient times liquorice is considered as an auspicious and valuable traditional medicine across the world for treatment of various ailments. Method: Several electronic online scientific databases such as Science Direct, PubMed, Scopus, Scifinder, Google Scholar, online books and reports were assessed for collecting information. All the collected information was classified into different sections to meet the objective of the paper. Results: The electronic database search yielded 3908 articles from different countries. Out of them one ninety-eight articles published between 1956 and 2021 were included, corresponding to all detailed review on G. glabra and research on anti-inflammatories, antivirals and immunomodulatory through pre-clinical and clinical models. From all selective area of studies on G. glabra and its bioactive components it was established (including molecular mechanisms) as a suitable remedy as per the current requirement of pandemic situation arise through respiratory tract infection. Conclusion: Different relevant studies have been thoroughly reviewed to gain an insight on utility of liquorice and its bioactive constituents for anti-inflammatories, antivirals and immunomodulatory effects with special emphasized for prevention and treatment of COVID-19 infection with possible mechanism of action at molecular level. Proposed directions for future research are also outlined to encourage researchers to find out various mechanistic targets and useful value added products of liquorice in future investigations.

Improving oral bioavailability of medicinal herbal compounds through lipid-based formulations - A Scoping Review.

BACKGROUND: Although numerous medicinal herbal compounds demonstrate promising therapeutic potential, their clinical application is often limited by their poor oral bioavailability. To circumvent this barrier, various lipid-based herbal formulations have been developed and trialled with promising experimental results. PURPOSE: This scoping review aims to describe the effect of lipid-based formulations on the oral bioavailability of herbal compounds. METHODS: A systematic search was conducted across three electronic databases (Medline, Embase and Cochrane Library) between January 2010 and January 2021 to identify relevant studies. The articles were rigorously screened for eligibility. Data from eligible studies were then extracted and collated for synthesis and descriptive analysis using Covidence. RESULTS: A total of 109 studies were included in the present review: 105 animal studies and four clinical trials. Among the formulations investigated, 50% were emulsions, 34% lipid particulate systems, 12% vesicular systems, and 4% were other types of lipid-based formulations. Within the emulsion system classification, self-emulsifying drug delivery systems were observed to produce the best improvements in oral bioavailability, followed by mixed micellar formulations. The introduction of composite lipid-based formulations and the use of uncommon surfactants such as sodium oleate in emulsion preparation was shown to consistently enhance the bioavailability of herbal compounds with poor oral absorption. Interestingly, the lipid-based formulations of magnesium lithospermate B and Pulsatilla chinensis produced an absolute bioavailability greater than 100% indicating the possibility of prolonged systemic circulation. With respect to chemical conjugation, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was the most frequently used and significantly improved the bioavailability of its phytoconstituents. CONCLUSION: Our findings suggest that there is no distinct lipid-based formulation superior to the other. Bioavailability improvements were largely dependent on the nature of the phytoconstituents. This scoping review, however, provided a detailed summary of the most up-to-date evidence on phytoconstituents formulated into lipid preparations and their oral bioavailability. We conclude that a systematic review and meta-analysis between bioavailability improvements of individual phytoconstituents (such as kaempferol, morin and myricetin) in various lipid-based formulations will provide a more detailed association. Such a review will be highly beneficial for both researchers and herbal manufacturers.

Indian Herb-Derived Phytoconstituent-Based Antiviral, Antimicrobial and Antifungal Formulation: An Oral Rinse Candidate for Oral Hygiene and the Potential Prevention of COVID-19 Outbreaks.

Outbreaks of emerging infectious diseases continue to challenge human health. Novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has triggered a global coronavirus pandemic, known as COVID-19. Multiple variants of SARS-CoV-2 virus are circulating, thus raising questions with respect to the effectiveness of different lines of treatment, such as vaccines and antiviral drugs. To find the appropriate prevention/treatment, 21 plant-based ingredients (Glycyrrhizin, Withanone, Aloe-emodin, Rhein, Emodin, Chrysophanol, Physcion, Kaempferol, Progallin A, Gallic acid, Naringin, Quercetin, Luteolin, and Apigenin) having antiviral, antibacterial and antifungal properties were identified. We pseudo-typed SARS-CoV-2 on a lentiviral vector plasmid and tested the impact of five different herbal formulations in mammalian HEK293T cells. Viral inactivation assay showed that the natural extracts in a herb-derived phytoconstituent-based formulation, BITS-003, comprising Bacopa monnieri, Glycyerrhiza glabra, Asparagus racemosus-wild, and Nigella sativa had strong virucidal properties, inactivating enveloped viruses from 2log10 (or 99%) to >4log10 (or 99.99%). Moreover, bacterial and yeast cells treated with BITS-003 displayed reduced growth. Topical use of the formulation as a mouthwash/gargle could be effective in reducing symptoms of respiratory viral infections, with the potential to decrease the viral load in the buccal/oral cavity. This may inhibit the coronavirus spreading to the lungs of infected persons and at the same time may reduce the risk of viral transmission to other susceptible persons through micro-droplets originating from the oral cavity of the infected person.

Discovery of Some Antiviral Natural Products to Fight Against Novel Coronavirus (SARS-CoV-2) Using an In silico Approach.

BACKGROUND: Novel coronavirus is a type of enveloped viruses with a single-stranded RNA enclosing helical nucleocapsid. The envelope consists of spikes on the surface which are made up of proteins through which virus enters into human cells. Until now, there is no specific drug or vaccine available to treat COVID-19 infection. In this scenario, reposting of drug or active molecules may provide rapid solution to fight against this deadly disease. OBJECTIVE: We selected 30 phytoconstituents from the different plants which are reported for antiviral activities against coronavirus (CoVs) and performed in silico screening to find out phytoconstituents which have potency to inhibit specific target of the novel coronavirus. METHODS: We performed molecular docking studies on three different proteins of novel coronavirus, namely COVID-19 main protease (3CL pro), papain-like protease (PL pro) and spike protein (S) attached to ACE2 binding domain. The screening of the phytoconstituents on the basis of binding affinity compared to standard drugs. The validations of screened compounds were done using ADMET and bioactivity prediction. RESULTS: We screened five compounds biscoclaurine, norreticuline, amentoflavone, licoricidin and myricetin, using in silico approach. All compounds were found safe in In silico toxicity studies. Bioactivity prediction reveals that these compounds may act through protease or enzyme inhibition. Results of compound biscoclaurine norreticuline were more interesting as this biscoclaurine had higher binding affinity for the target 3CLpro and PLpro targets and norreticuline had a higher binding affinity for the target PLpro and Spike protein. CONCLUSION: Our study concludes that these compounds could be further explored rapidly as it may have potential to fight against COVID-19.

Medicinal Plants and Isolated Molecules Demonstrating Immunomodulation Activity as Potential Alternative Therapies for Viral Diseases Including COVID-19.

Plants have been extensively studied since ancient times and numerous important chemical constituents with tremendous therapeutic potential are identified. Attacks of microorganisms including viruses and bacteria can be counteracted with an efficient immune system and therefore, stimulation of body's defense mechanism against infections has been proven to be an effective approach. Polysaccharides, terpenoids, flavonoids, alkaloids, glycosides, and lactones are the important phytochemicals, reported to be primarily responsible for immunomodulation activity of the plants. These phytochemicals may act as lead molecules for the development of safe and effective immunomodulators as potential remedies for the prevention and cure of viral diseases. Natural products are known to primarily modulate the immune system in nonspecific ways. A number of plant-based principles have been identified and isolated with potential immunomodulation activity which justify their use in traditional folklore medicine and can form the basis of further specified research. The aim of the current review is to describe and highlight the immunomodulation potential of certain plants along with their bioactive chemical constituents. Relevant literatures of recent years were searched from commonly employed scientific databases on the basis of their ethnopharmacological use. Most of the plants displaying considerable immunomodulation activity are summarized along with their possible mechanisms. These discussions shall hopefully elicit the attention of researchers and encourage further studies on these plant-based immunomodulation products as potential therapy for the management of infectious diseases, including viral ones such as COVID-19.