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1.
Molecules ; 26(24)2021 Dec 09.
Article in English | MEDLINE | ID: covidwho-1572567

ABSTRACT

COVID-19 is the name of the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that occurred in 2019. The virus-host-specific interactions, molecular targets on host cell deaths, and the involved signaling are crucial issues, which become potential targets for treatment. Spike protein, angiotensin-converting enzyme 2 (ACE2), cathepsin L-cysteine peptidase, transmembrane protease serine 2 (TMPRSS2), nonstructural protein 1 (Nsp1), open reading frame 7a (ORF7a), viral main protease (3C-like protease (3CLpro) or Mpro), RNA dependent RNA polymerase (RdRp) (Nsp12), non-structural protein 13 (Nsp13) helicase, and papain-like proteinase (PLpro) are molecules associated with SARS-CoV infection and propagation. SARS-CoV-2 can induce host cell death via five kinds of regulated cell death, i.e., apoptosis, necroptosis, pyroptosis, autophagy, and PANoptosis. The mechanisms of these cell deaths are well established and can be disrupted by synthetic small molecules or natural products. There are a variety of compounds proven to play roles in the cell death inhibition, such as pan-caspase inhibitor (z-VAD-fmk) for apoptosis, necrostatin-1 for necroptosis, MCC950, a potent and specific inhibitor of the NLRP3 inflammasome in pyroptosis, and chloroquine/hydroxychloroquine, which can mitigate the corresponding cell death pathways. However, NF-κB signaling is another critical anti-apoptotic or survival route mediated by SARS-CoV-2. Such signaling promotes viral survival, proliferation, and inflammation by inducing the expression of apoptosis inhibitors such as Bcl-2 and XIAP, as well as cytokines, e.g., TNF. As a result, tiny natural compounds functioning as proteasome inhibitors such as celastrol and curcumin can be used to modify NF-κB signaling, providing a responsible method for treating SARS-CoV-2-infected patients. The natural constituents that aid in inhibiting viral infection, progression, and amplification of coronaviruses are also emphasized, which are in the groups of alkaloids, flavonoids, terpenoids, diarylheptanoids, and anthraquinones. Natural constituents derived from medicinal herbs have anti-inflammatory and antiviral properties, as well as inhibitory effects, on the viral life cycle, including viral entry, replication, assembly, and release of COVID-19 virions. The phytochemicals contain a high potential for COVID-19 treatment. As a result, SARS-CoV-2-infected cell death processes and signaling might be of high efficacy for therapeutic targeting effects and yielding encouraging outcomes.


Subject(s)
COVID-19/drug therapy , Cell Death/drug effects , Drug Discovery/methods , Molecular Targeted Therapy/methods , SARS-CoV-2/drug effects , Amino Acid Chloromethyl Ketones/pharmacology , Antiviral Agents/pharmacology , Apoptosis/drug effects , Furans/pharmacology , Humans , Hydroxychloroquine/pharmacology , Imidazoles/pharmacology , Indenes/pharmacology , Indoles/pharmacology , Necroptosis/drug effects , Phytochemicals/pharmacology , Pyroptosis/drug effects , SARS-CoV-2/metabolism , Signal Transduction/drug effects , Sulfonamides/pharmacology , Viral Proteins/antagonists & inhibitors
2.
J Microbiol ; 59(11): 959-977, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1491414

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has underscored the lack of approved drugs against acute viral diseases. Plants are considered inexhaustible sources of drugs for several diseases and clinical conditions, but plant-derived compounds have seen little success in the field of antivirals. Here, we present the case for the use of compounds from vascular plants, including alkaloids, flavonoids, polyphenols, and tannins, as antivirals, particularly for the treatment of COVID-19. We review current evidence for the use of these phytochemicals against SARS-CoV-2 infection and present their potential targets in the SARS-CoV-2 replication cycle.


Subject(s)
Antiviral Agents , COVID-19/drug therapy , Pandemics , Phytochemicals , SARS-CoV-2/drug effects , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Chlorocebus aethiops , HEK293 Cells , Humans , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Vero Cells
3.
Molecules ; 26(20)2021 Oct 15.
Article in English | MEDLINE | ID: covidwho-1480885

ABSTRACT

In our in vitro and in vivo studies, we used Acalypha indica root methanolic extract (AIRME), and investigated their free radical scavenging/antioxidant and anti-inflammatory properties. Primarily, phytochemical analysis showed rich content of phenols (70.92 mg of gallic acid/g) and flavonoids (16.01 mg of rutin/g) in AIRME. We then performed HR-LC-MS and GC-MS analyses, and identified 101 and 14 phytochemical compounds, respectively. Among them, ramipril glucuronide (1.563%), antimycin A (1.324%), swietenine (1.134%), quinone (1.152%), oxprenolol (1.118%), choline (0.847%), bumetanide (0.847%) and fenofibrate (0.711%) are the predominant phytomolecules. Evidence from in vitro studies revealed that AIRME scavenges DPPH and hydroxyl radicals in a concentration dependent manner (10-50 µg/mL). Similarly, hydrogen peroxide and lipid peroxidation were also remarkably inhibited by AIRME as concentration increases (20-100 µg/mL). In vitro antioxidant activity of AIRME was comparable to ascorbic acid treatment. For in vivo studies, carrageenan (1%, sub-plantar) was injected to rats to induce localized inflammation. Acute inflammation was represented by paw-edema, and significantly elevated (p < 0.05) WBC, platelets and C-reactive protein (CRP). However, AIRME pretreatment (150/300 mg/kg bodyweight) significantly (p < 0.05) decreased edema volume. This was accompanied by a significant (p < 0.05) reduction of WBC, platelets and CRP with both doses of AIRME. The decreased activities of superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase in paw tissue were restored (p < 0.05 / p < 0.01) with AIRME in a dose-dependent manner. Furthermore, AIRME attenuated carrageenan-induced neutrophil infiltrations and vascular dilation in paw tissue. For the first time, our findings demonstrated the potent antioxidant and anti-inflammatory properties of AIRME, which could be considered to develop novel anti-inflammatory drugs.


Subject(s)
Acalypha/chemistry , Phytochemicals/chemistry , Phytochemicals/pharmacology , Plants, Medicinal/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Disease Models, Animal , Edema/drug therapy , Edema/enzymology , Edema/pathology , Free Radical Scavengers/chemistry , Free Radical Scavengers/pharmacology , In Vitro Techniques , Male , Phytotherapy , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Roots/chemistry , Rats , Rats, Wistar
4.
Phytother Res ; 35(10): 5384-5396, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1479438

ABSTRACT

The current pandemic responsible for the crippling of the health care system is caused by the novel SARS-CoV-2 in 2019 and leading to coronavirus disease 2019 (COVID-19). The virus enters into humans by attachment of its Spike protein (S) to the ACE receptor present on the lung epithelial cell surface followed by cleavage of S protein by the cellular transmembrane serine protease (TMPRSS2). After entry, the SARS-CoV-2 RNA genome is released into the cytosol, where it highjacks host replication machinery for viral replication, assemblage, as well as the release of new viral particles. The major drug targets that have been identified for SARS-CoV-2 through host-virus interaction studies include 3CLpro, PLpro, RNA-dependent RNA polymerase, and S proteins. Several reports of natural compounds along with synthetic products have displayed promising results and some of them are Tripterygium wilfordii, Pudilan Xiaoyan Oral Liquid, Saponin derivates, Artemisia annua, Glycyrrhiza glabra L., Jinhua Qinggan granules, Xuebijing, and Propolis. This review attempts to disclose the natural products identified as anti-SARS-CoV-2 based on in silico prediction and the effect of a variety of phytochemicals either alone and/or in combination with conventional treatments along with their possible molecular mechanisms involved for both prevention and treatment of the SARS-CoV-2 disease.


Subject(s)
Antiviral Agents , Biological Products , COVID-19 , Drugs, Chinese Herbal , SARS-CoV-2/drug effects , Antiviral Agents/pharmacology , Biological Products/pharmacology , COVID-19/drug therapy , Drugs, Chinese Herbal/pharmacology , Humans , Phytochemicals/pharmacology
5.
Sci Rep ; 11(1): 20295, 2021 10 13.
Article in English | MEDLINE | ID: covidwho-1467129

ABSTRACT

Novel SARS-CoV-2, an etiological factor of Coronavirus disease 2019 (COVID-19), poses a great challenge to the public health care system. Among other druggable targets of SARS-Cov-2, the main protease (Mpro) is regarded as a prominent enzyme target for drug developments owing to its crucial role in virus replication and transcription. We pursued a computational investigation to identify Mpro inhibitors from a compiled library of natural compounds with proven antiviral activities using a hierarchical workflow of molecular docking, ADMET assessment, dynamic simulations and binding free-energy calculations. Five natural compounds, Withanosides V and VI, Racemosides A and B, and Shatavarin IX, obtained better binding affinity and attained stable interactions with Mpro key pocket residues. These intermolecular key interactions were also retained profoundly in the simulation trajectory of 100 ns time scale indicating tight receptor binding. Free energy calculations prioritized Withanosides V and VI as the top candidates that can act as effective SARS-CoV-2 Mpro inhibitors.


Subject(s)
COVID-19/drug therapy , Coronavirus 3C Proteases/metabolism , Phytochemicals/pharmacology , Antiviral Agents/pharmacology , Computational Biology/methods , Coronavirus 3C Proteases/drug effects , Coronavirus 3C Proteases/ultrastructure , Drug Evaluation, Preclinical/methods , Humans , Molecular Docking Simulation/methods , Molecular Dynamics Simulation , Peptide Hydrolases/drug effects , Phytochemicals/metabolism , Protease Inhibitors/pharmacology , Protein Binding/drug effects , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity
6.
Comput Biol Med ; 136: 104758, 2021 09.
Article in English | MEDLINE | ID: covidwho-1406242

ABSTRACT

Covid-19 is an emerging infectious disease caused by coronavirus SARS-CoV-2. Due to the rapid rise in deaths resulted from this infection all around the world, the identification of drugs against this new coronavirus is an important requirement. Among the drugs that can fight this type of infection; natural products are substances that serve as sources of beneficial chemical molecules for the development of effective therapies. In this study, Camphor, Artemisinin and 14 Sumac phytochemicals were docked in the active site of SARS-CoV-2 main protease (PDB code: 6LU7). We have also performed molecular dynamic simulation at 100 ns with MM-GBSA/PBSA analysis for the structures with the best affinity in the binding site of the studied enzyme (Hinokiflavone and Myricetin) after docking calculations to consider parameters like RMSD, covariance, PCA, radius of gyration, potential energy, temperature and pressure. The result indicates that Hinokiflavone and Myricetin are the structures with best affinity and stability in the binding site of the studied enzyme and they respect the conditions mentioned in Lipinski's rule and have acceptable ADMET proprieties; so, these compounds have important pharmacokinetic properties and bioavailability, and they could have more potent antiviral treatment of COVID-19 than the other studied compounds.


Subject(s)
Artemisinins , COVID-19 , Rhus , Camphor , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Phytochemicals/pharmacology , Protease Inhibitors , SARS-CoV-2
7.
Molecules ; 26(17)2021 Aug 25.
Article in English | MEDLINE | ID: covidwho-1399347

ABSTRACT

Lippia graveolens is a traditional crop and a rich source of bioactive compounds with various properties (e.g., antioxidant, anti-inflammatory, antifungal, UV defense, anti-glycemic, and cytotoxicity) that is primarily cultivated for essential oil recovery. The isolated bioactive compounds could be useful as additives in the functional food, nutraceuticals, cosmetics, and pharmaceutical industries. Carvacrol, thymol, ß-caryophyllene, and p-cymene are terpene compounds contained in oregano essential oil (OEO); flavonoids such as quercetin O-hexoside, pinocembrin, and galangin are flavonoids found in oregano extracts. Furthermore, thermoresistant compounds that remain in the plant matrix following a thermal process can be priced in terms of the circular economy. By using better and more selective extraction conditions, the bioactive compounds present in Mexican oregano can be studied as potential inhibitors of COVID-19. Also, research on extraction technologies should continue to ensure a higher quality of bioactive compounds while preventing an undesired chemical shift (e.g., hydrolysis). The oregano fractions can be used in the food, health, and agricultural industries.


Subject(s)
Lippia/chemistry , Phytochemicals/therapeutic use , Plant Extracts/therapeutic use , COVID-19/drug therapy , Cosmetics , Dietary Supplements , Functional Food , Humans , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , SARS-CoV-2/drug effects
8.
Eur J Pharmacol ; 890: 173648, 2021 Jan 05.
Article in English | MEDLINE | ID: covidwho-1385504

ABSTRACT

In an attempt to search for selective inhibitors against the SARS-CoV-2 which caused devastating of lives and livelihoods across the globe, 415 natural metabolites isolated from several plants, fungi and bacteria, belonging to different classes, were investigated. The drug metabolism and safety profiles were computed in silico and the results showed seven compounds namely fusaric acid, jasmonic acid, jasmonic acid methyl ester, putaminoxin, putaminoxin B and D, and stagonolide K were predicted to having considerable absorption, metabolism, distribution and excretion parameters (ADME) and safety indices. Molecular docking against the receptor binding domain (RBD) of spike glycoprotein (S1) and the main protease (Mpro) exposed the compounds having better binding affinity to main protease as compared to the S1 receptor binding domain. The docking results were compared to an antiviral drug penciclovir reportedly of clinical significance in treating the SARS-CoV-2 infected patients. The results demonstrated the test compounds jasmonic acid, putaminoxins B and D bound to the HIS-CYS catalytic dyad as well as to other residues within the MPro active site with much greater affinity than penciclovir. The findings of the study suggest that these compounds could be explored as potential SARS-CoV-2 inhibitors, and could further be combined with the experimental investigations to develop effective therapeutics to deal with the present pandemic.


Subject(s)
Antiviral Agents/pharmacology , Biological Products/pharmacology , Coronavirus 3C Proteases/metabolism , Phytochemicals/pharmacology , Protease Inhibitors/pharmacology , Spike Glycoprotein, Coronavirus/metabolism , Antiviral Agents/pharmacokinetics , Bacteria/metabolism , Biological Products/pharmacokinetics , Blood-Brain Barrier/metabolism , Coronavirus 3C Proteases/antagonists & inhibitors , Cyclopentanes/pharmacokinetics , Cyclopentanes/pharmacology , Fungi/metabolism , Humans , Intestinal Absorption , Lactones/pharmacokinetics , Lactones/pharmacology , Molecular Docking Simulation , Molecular Dynamics Simulation , Oxylipins/pharmacokinetics , Oxylipins/pharmacology , Phytochemicals/pharmacokinetics , Plants/metabolism , Protease Inhibitors/pharmacokinetics , Protein Binding , Protein Domains , SARS-CoV-2
9.
BMC Complement Med Ther ; 21(1): 219, 2021 Sep 01.
Article in English | MEDLINE | ID: covidwho-1383623

ABSTRACT

BACKGROUND: Pears have been world-widely used as a sweet and nutritious food and a folk medicine for more than two millennia. METHODS: We conducted a review from ancient literatures to current reports to extract evidence-based functions of pears. RESULTS: We found that pears have many active compounds, e.g., flavonoids, triterpenoids, and phenolic acids including arbutin, chlorogenic acid, malaxinic acid, etc. Most of researchers agree that the beneficial compounds are concentrated in the peels. From various in vitro, in vivo, and human studies, the medicinal functions of pears can be summarized as anti-diabetic,-obese, -hyperlipidemic, -inflammatory, -mutagenic, and -carcinogenic effects, detoxification of xenobiotics, respiratory and cardio-protective effects, and skin whitening effects. Therefore, pears seem to be even effective for prevention from Covid-19 or PM2.5 among high susceptible people with multiple underlying diseases. CONCLUSION: For the current or post Covid-19 era, pears have potential for functional food or medicine for both of communicable and non-communicable disease.


Subject(s)
Fruit/chemistry , Functional Food , Phytochemicals/pharmacology , Pyrus/chemistry , COVID-19 , Flavonoids , Humans , Phenols , Triterpenes
10.
Bratisl Lek Listy ; 122(9): 670-679, 2021.
Article in English | MEDLINE | ID: covidwho-1380031

ABSTRACT

BACKGROUND: Predominant molecules in Peganum harmala leaves were detected using gas chromatography-mass spectrometry (GC-MS). Based on the results of this analysis, most alkaloids, flavonoids and triterpenoids in found P. harmala was compiled from the literature in order to develop and lead the production of effective inhibitor drugs for ACE2, main protease, and RNA dependent RNA polymerase (RdRp) proteins of SARS-CoV-2 virus, which is today's most contagious and deadly disease. AIM: By comparing FDA-approved drugs used in the treatment of COVID-19, we aimed to determine whether the molecules in P. harmala are effective against SARS CoV-2 in silico. RESULTS AND CONCLUSION: P. harmala molecules were selected as drug candidates from the PubChem web tool. Afterwards, molecular docking calculations of these inhibitor molecules were made with Maestro Molecular modeling program by Schrödinger. The comparison of molecules with high inhibitory activities with FDA-approved drugs was made. With molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations, docking calculations of molecules that have high inhibitory activity, were tried to be verified by calculations in the range of 0-100 nanoseconds (Tab. 4, Fig. 6, Ref. 53).


Subject(s)
Alkaloids , Peganum , SARS-CoV-2/drug effects , Alkaloids/pharmacology , COVID-19 , Humans , Molecular Docking Simulation , Peganum/chemistry , Phytochemicals/pharmacology , Plant Leaves/chemistry
11.
Comput Biol Med ; 137: 104818, 2021 10.
Article in English | MEDLINE | ID: covidwho-1372943

ABSTRACT

BACKGROUND: This world is currently witnessing a pandemic outbreak of 'COVID-19' caused by a positive-strand RNA virus 'SARS-CoV-2'. Millions have succumbed globally to the disease, and the numbers are increasing day by day. The viral genome enters into the human host through interaction between the spike protein (S) and host angiotensin-converting enzyme-2 (ACE2) proteins. S is the common target for most recently rolled-out vaccines across regions. A recent surge in single/multiple mutations in S region is of great concern as it may escape vaccine induced immunity. So far, the treatment regime with repurposed drugs has not been too successful. HYPOTHESIS: Natural compounds are capable of targeting mutated spike protein by binding to its active site and destabilizing the spike-host ACE2 interaction. MATERIALS AND METHODS: A hypothetical mutated spike protein was constructed by incorporating twelve different mutations from twelve geographical locations simultaneously into the receptor-binding domain (RBD) and docked with ACE2 and seven phytochemicals namely allicin, capsaicin, cinnamaldehyde, curcumin, gingerol, piperine and zingeberene. Molecular Dynamic (MD) simulation and Principal Component Analysis (PCA) were finally used for validation of the docking results. RESULT: The docking results showed that curcumin and piperine were most potent to bind ACE2, mutated spike, and mutated spike-ACE2 complex, thereby restricting viral entry. ADME analysis also proved their drug candidature. The docking complexes were found to be stable by MD simulation. CONCLUSION: This result provides a significant insight about the phytochemicals' role, namely curcumin and piperine, as the potential therapeutic entities against mutated spike protein of SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Molecular Docking Simulation , Phytochemicals/pharmacology
12.
Biomolecules ; 11(8)2021 08 23.
Article in English | MEDLINE | ID: covidwho-1367768

ABSTRACT

In 2019, COVID-19 emerged as a severe respiratory disease that is caused by the novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The disease has been associated with high mortality rate, especially in patients with comorbidities such as diabetes, cardiovascular and kidney diseases. This could be attributed to dysregulated immune responses and severe systemic inflammation in COVID-19 patients. The use of effective antiviral drugs against SARS-CoV-2 and modulation of the immune responses could be a potential therapeutic strategy for COVID-19. Studies have shown that natural phenolic compounds have several pharmacological properties, including anticoronavirus and immunomodulatory activities. Therefore, this review discusses the dual action of these natural products from the perspective of applicability at COVID-19.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Flavonoids/therapeutic use , Immunologic Factors/therapeutic use , Phytochemicals/therapeutic use , Protease Inhibitors/therapeutic use , Animals , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Coronavirus/drug effects , Flavonoids/chemistry , Flavonoids/pharmacology , Humans , Immunologic Factors/chemistry , Immunologic Factors/pharmacology , Phytochemicals/chemistry , Phytochemicals/pharmacology , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology
13.
Pharmacol Res ; 163: 105224, 2021 01.
Article in English | MEDLINE | ID: covidwho-1364404

ABSTRACT

Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) as common life-threatening lung diseases with high mortality rates are mostly associated with acute and severe inflammation in lungs. With increasing in-depth studies of ALI/ARDS, significant breakthroughs have been made, however, there are still no effective pharmacological therapies for treatment of ALI/ARDS. Especially, the novel coronavirus pneumonia (COVID-19) is ravaging the globe, and causes severe respiratory distress syndrome. Therefore, developing new drugs for therapy of ALI/ARDS is in great demand, which might also be helpful for treatment of COVID-19. Natural compounds have always inspired drug development, and numerous natural products have shown potential therapeutic effects on ALI/ARDS. Therefore, this review focuses on the potential therapeutic effects of natural compounds on ALI and the underlying mechanisms. Overall, the review discusses 159 compounds and summarizes more than 400 references to present the protective effects of natural compounds against ALI and the underlying mechanism.


Subject(s)
Acute Lung Injury/drug therapy , Lung/drug effects , Phytochemicals/pharmacology , Respiratory Distress Syndrome/drug therapy , Acute Lung Injury/etiology , Acute Lung Injury/metabolism , Acute Lung Injury/pathology , Animals , Humans , Lung/metabolism , Lung/pathology , Phytochemicals/isolation & purification , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/metabolism , Respiratory Distress Syndrome/pathology , Signal Transduction
14.
Int J Mol Sci ; 22(16)2021 Aug 18.
Article in English | MEDLINE | ID: covidwho-1360776

ABSTRACT

The year 2020 became the year of the outbreak of coronavirus, SARS-CoV-2, which escalated into a worldwide pandemic and continued into 2021. One of the unique symptoms of the SARS-CoV-2 disease, COVID-19, is the loss of chemical senses, i.e., smell and taste. Smell training is one of the methods used in facilitating recovery of the olfactory sense, and it uses essential oils of lemon, rose, clove, and eucalyptus. These essential oils were not selected based on their chemical constituents. Although scientific studies have shown that they improve recovery, there may be better combinations for facilitating recovery. Many phytochemicals have bioactive properties with anti-inflammatory and anti-viral effects. In this review, we describe the chemical compounds with anti- inflammatory and anti-viral effects, and we list the plants that contain these chemical compounds. We expand the review from terpenes to the less volatile flavonoids in order to propose a combination of essential oils and diets that can be used to develop a new taste training method, as there has been no taste training so far. Finally, we discuss the possible use of these in clinical settings.


Subject(s)
Ageusia/drug therapy , Ageusia/virology , Anosmia/drug therapy , Anosmia/virology , COVID-19/drug therapy , Phytochemicals/therapeutic use , Ageusia/metabolism , Anosmia/diagnosis , Anosmia/metabolism , COVID-19/complications , Humans , Phytochemicals/pharmacology , SARS-CoV-2/isolation & purification
15.
Curr Opin Pharmacol ; 60: 200-207, 2021 10.
Article in English | MEDLINE | ID: covidwho-1347566

ABSTRACT

Lonicerae japonicae flos (LJF), known as Jin Yin Hua in Chinese, is one of the most commonly used traditional Chinese herbs and nutraceuticals. Nowadays, LJF is broadly applied in an array of afflictions, such as fever, sore throat, flu infection, cough, and arthritis, with the action mechanism to be elucidated. Here, we strove to summarize the main phytochemical components of LJF and review its updated pharmacological effects, including inhibition of inflammation, pyrexia, viruses, and bacteria, immunoregulation, and protection of the liver, nervous system, and heart, with a focus on the potential efficacy of LJF on coronavirus disease-2019 based on network pharmacology so as to fully underpin the utilization of LJF as a medicinal herb and a favorable nutraceutical in daily life.


Subject(s)
COVID-19/drug therapy , Drugs, Chinese Herbal/pharmacology , Plant Extracts/pharmacology , Humans , Lonicera , Phytochemicals/pharmacology , SARS-CoV-2/drug effects
16.
Comput Biol Med ; 136: 104683, 2021 09.
Article in English | MEDLINE | ID: covidwho-1333335

ABSTRACT

Coronavirus Disease-2019 (COVID-19), a viral disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was declared a global pandemic by WHO in 2020. In this scenario, SARS-CoV-2 main protease (COVID-19 Mpro), an enzyme mainly involved in viral replication and transcription is identified as a crucial target for drug discovery. Traditionally used medicinal plants contain a large amount of bioactives and pave a new path to develop drugs and medications for COVID-19. The present study was aimed to examine the potential of Emblica officinalis (amla), Phyllanthus niruri Linn. (bhumi amla) and Tinospora cordifolia (giloy) bioactive compounds to inhibit the enzymatic activity of COVID-19 Mpro. In total, 96 bioactive compounds were selected and docked with COVID-19 Mpro and further validated by molecular dynamics study. From the docking and molecular dynamics study, it was revealed that the bioactives namely amritoside, apigenin-6-C-glucosyl7-O-glucoside, pectolinarin and astragalin showed better binding affinities with COVID-19 Mpro. Drug-likeness, ADEMT and bioactivity score prediction of best drug candidates were evaluated by DruLiTo, pkCSM and Molinspiration servers, respectively. Overall, the in silico results confirmed that the validated bioactives could be exploited as promising COVID-19 Mpro inhibitors.


Subject(s)
Phyllanthus emblica , Phyllanthus , Protease Inhibitors/pharmacology , SARS-CoV-2/drug effects , Tinospora , COVID-19 , Coronavirus 3C Proteases/antagonists & inhibitors , Humans , Medicine, Ayurvedic , Molecular Docking Simulation , Molecular Dynamics Simulation , Peptide Hydrolases , Phyllanthus/chemistry , Phyllanthus emblica/chemistry , Phytochemicals/pharmacology , Plants, Medicinal/chemistry , Tinospora/chemistry
17.
Phytother Res ; 35(8): 4284-4296, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1161639

ABSTRACT

The review article serves as a mini directory of medicinal plants (662 medicinal plants have been identified) that have been investigated for antiviral property between 2015 and 2019. Data have been extracted from Scopus using specific keywords followed by manual sorting to avoid any duplication. Critical analyses of handpicked data have been presented. Mapping of medicinal plants, followed by critical analysis on the families and plant parts investigated in the said tenure, and its correlation with the participating countries and virus types have been critically analyzed. Interceptive role of phytochemicals in impeding viral replication has also been taken note of. Emphasis on India's exploration of various medicinal plants has also been given. Also presents a tutelage, which is likely to revive the interest in natural products for search of potential antivirals. This review is expected to serve as a rich data bank and as a guiding principle for researchers who are planning to explore medicinal plants in search for potential antiviral. It is time that researchers need to revisit their countries' own history of traditional medicine to predict something worthful in future.


Subject(s)
Antiviral Agents/pharmacology , Phytochemicals/pharmacology , Plants, Medicinal , Humans , Medicine, Traditional , Phytotherapy , Plant Extracts
18.
Expert Rev Clin Pharmacol ; 14(10): 1305-1315, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1322577

ABSTRACT

BACKGROUND: The high transmission and pathogenicity of SARS-CoV-2 has led to a pandemic that has halted the world's economy and health. The newly evolved strains and scarcity of vaccines has worsened the situation. The main protease (Mpro) of SARS-CoV-2 can act as a potential target due to its role in viral replication and conservation level. METHODS: In this study, we have enlisted more than 1100 phytochemicals from Asian plants based on deep literature mining. The compounds library was screened against the Mpro of SARS-CoV-2. RESULTS: The selected three ligands, Flemichin, Delta-Oleanolic acid, and Emodin 1-O-beta-D-glucoside had a binding energy of -8.9, -8.9, -8.7 KJ/mol respectively. The compounds bind to the active groove of the main protease at; Cys145, Glu166, His41, Met49, Pro168, Met165, Gln189. The multiple descriptors from the simulation study; root mean square deviation, root mean square fluctuation, radius of gyration, hydrogen bond, solvent accessible surface area confirms the stable nature of the protein-ligand complexes. Furthermore, post-md analysis confirms the rigidness in the docked poses over the simulation trajectories. CONCLUSIONS: Our combinatorial drug design approaches may help researchers to identify suitable drug candidates against SARS-CoV-2.


Subject(s)
Antiviral Agents/pharmacology , Drug Discovery , Phytochemicals/pharmacology , SARS-CoV-2/enzymology , Viral Proteases/metabolism , Antiviral Agents/chemistry , Databases, Chemical , Gene Expression Regulation, Viral/drug effects , Molecular Docking Simulation , Molecular Structure , Phytochemicals/chemistry , Viral Proteases/genetics
19.
Comput Biol Med ; 136: 104671, 2021 09.
Article in English | MEDLINE | ID: covidwho-1322055

ABSTRACT

Antiviral culinary plants are potential bioresources for preventive nutraceuticals and/or antiviral drugs in COVID-19. Structure-based virtual screening was undertaken to screen 173 compounds previously reported from Vernonia amygdalina and Occinum gratissimum for direct interaction with the active site of the 3-Chymotrypsin-Like Protease (3CLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on docking scores and comparison with reference inhibitors, a hit-list of 10 top phytocompounds was defined, which also had strong interactions with the catalytic centre of 3CLpro from three related strains of coronavirus (SARS-CoV, MERS-CoV, HKU4). Among these, six compounds (neoandrographolide, vernolide, isorhamnetin, chicoric acid, luteolin, and myricetin) exhibited the highest binding tendencies to the equilibrated conformers of SARS-CoV-2 3CLpro in an in-depth docking analysis to 5 different representative conformations from the cluster analysis of the molecular dynamics simulation (MDS) trajectories of the protein. In silico drug-likeness analyses revealed two drug-like terpenoids viz: neoandrographolide and vernolide as promising inhibitors of SARS-CoV-2 3CLpro. These structures were accommodated within the substrate-binding pocket; and interacted with the catalytic dyad (Cys145 and His41), the oxyanion loop (residues 138-145), and the S1/S2 sub-sites of the enzyme active site through the formation of an array of hydrogen bonds and hydrophobic interactions. Molecular dynamics simulation and binding free energy calculation revealed that the terpenoid-enzyme complexes exhibit strong interactions and structural stability. Therefore, these compounds may stabilize the conformation of the flexible oxyanion loop; and thereby interfere with the tetrahedral oxyanion intermediate formation during the proteolytic activity of the enzyme.


Subject(s)
Antiviral Agents/pharmacology , Coronavirus 3C Proteases/antagonists & inhibitors , Ocimum/chemistry , Phytochemicals/pharmacology , SARS-CoV-2/drug effects , Vernonia , COVID-19 , Chymases , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Protease Inhibitors , Vernonia/chemistry
20.
J Biomol Struct Dyn ; 39(12): 4415-4426, 2021 08.
Article in English | MEDLINE | ID: covidwho-1317839

ABSTRACT

The outbreak due to SARS-CoV-2 (or Covid-19) is spreading alarmingly and number of deaths due to infection is aggressively increasing every day. Due to the rapid human to human transmission of Covid-19, we are in need to find a potent drug at the earliest by ruling-out the traditional time-consuming approach of drug development. This is only possible if we use reliable computational approaches for screening compounds from chemical space or by drug repurposing or by finding the phytochemicals and nutraceuticals from plants as they can be immediately used without the need for carrying out drug-trials to test safety and efficacy. A number of plant products were routinely suggested as drugs in traditional Indian and Chinese medicine. Here using molecular docking approach, and combined molecular dynamics and MM-GBSA based free energy calculations approach, we study the potency of the four selected phytochemicals namely andrographolide (AGP1), 14-deoxy 11,12-didehydro andrographolide (AGP2), neoandrographolide (AGP3) and 14-deoxy andrographolide (AGP4) from A. paniculata plant against the four key targets including three non-structural proteins (3 L main protease (3CLpro), Papain-like proteinase (PLpro) and RNA-directed RNA polymerase (RdRp)) and a structural protein (spike protein (S)) of the virus which are responsible for replication, transcription and host cell recognition. The therapeutic potential of the selected phytochemicals against Covid-19 were also evaluated in comparison with a few commercially available drugs. The binding free energy data suggest that AGP3 could be used as a cost-effective drug-analog for treating covid-19 infection in developing countries.Communicated by Ramaswamy H. Sarma.


Subject(s)
Andrographis , COVID-19 , Pharmaceutical Preparations , Antiviral Agents/pharmacology , Humans , Molecular Docking Simulation , Phytochemicals/pharmacology , SARS-CoV-2
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