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1.
Molecules ; 27(13)2022 Jun 26.
Article in English | MEDLINE | ID: covidwho-1934173

ABSTRACT

The purpose of this study was to find the biological propensities of the vegetable plant Pleurospermum candollei by investigating its phytochemical profile and biological activities. Phytochemical analysis was done by spectroscopic methods to investigate the amount of total polyphenols, and biological evaluation was done by the different antioxidant, enzyme inhibitory (tyrosinase, α-amylase, and α-glucosidase), thrombolytic, and antibacterial activities. The highest amount of total phenolic and flavonoid contents was observed in methanolic extract (240.69 ± 2.94 mg GAE/g and 167.59 ± 3.47 mg QE/g); the fractions showed comparatively less quantity (57.02 ± 1.31 to 144.02 ± 2.11 mg GAE/g, and 48.21 ± 0.75 to 96.58 ± 2.30 mg QE/g). The effect of these bioactive contents was also related to biological activities. GCMS analysis led to the identification of bioactive compounds with different biological effects from methanolic extract (antioxidant; 55.07%, antimicrobial; 56.41%), while the identified compounds from the n-hexane fraction with antioxidant properties constituted 67.86%, and those with antimicrobial effects constituted 82.95%; however, the synergetic effect of polyphenols may also have contributed to the highest value of biological activities of methanolic extract. Molecular docking was also performed to understand the relationship of identified secondary metabolites with enzyme-inhibitory activities. The thrombolytic activity was also significant (40.18 ± 1.80 to 57.15 ± 1.10 % clot lysis) in comparison with streptokinase (78.5 ± 1.53 to 82.34 ± 1.25% clot lysis). Methanolic extract also showed good activity against Gram-positive strains of bacteria, and the highest activity was observed against Bacillus subtilis. The findings of this study will improve our knowledge of phytochemistry, and biological activities of P. candollei, which seems to be a ray of hope to design formulations of natural products for the improvement of health and prevention of chronic diseases; however, further research may address the development of novel drugs for use in pharmaceuticals.


Subject(s)
Anti-Infective Agents , Apiaceae , Biological Products , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Biological Products/pharmacology , Methanol/chemistry , Molecular Docking Simulation , Phytochemicals/chemistry , Phytochemicals/pharmacology , Plant Extracts/chemistry , Plant Extracts/pharmacology , Polyphenols/pharmacology
2.
PLoS One ; 17(6): e0268454, 2022.
Article in English | MEDLINE | ID: covidwho-1892318

ABSTRACT

This study aims to investigate the binding potential of chemical compounds of Senna in comparison with the experimentally tested active phytochemicals against SARS-CoV-2 protein targets to assist in prevention of infection by exploring multiple treatment options. The entire set of phytochemicals from both the groups were subjected to advanced computational analysis that explored functional molecular descriptors from a set of known medicinal-based active therapeutics followed by MD simulations on multiple SARS-CoV-2 target proteins. Our findings manifest the importance of hydrophobic substituents in chemical structures of potential inhibitors through cross-validation with the FDA-approved anti-3CLpro drugs. Noteworthy improvement in end-point binding free energies and pharmacokinetic profiles of the proposed compounds was perceived in comparison to the control drug, vizimpro. Moreover, the identification of common drug targets namely; AKT1, PTGS1, TNF, and DPP4 between proposed active phytochemicals and Covid19 using network pharmacological analysis further substantiate the importance of medicinal scaffolds. The structural dynamics and binding affinities of phytochemical compounds xanthoangelol_E, hesperetin, and beta-sitosterol reported as highly potential against 3CLpro in cell-based and cell-free assays are consistent with the computational analysis. Whereas, the secondary metabolites such as sennosides A, B, C, D present in higher amount in Senna exhibited weak binding affinity and instability against the spike protein, helicase nsp13, RdRp nsp12, and 3CLpro. In conclusion, the results contravene fallacious efficacy claims of Senna tea interventions circulating on electronic/social media as Covid19 cure; thus emphasizing the importance of well-examined standardized data of the natural products in hand; thereby preventing unnecessary deaths under pandemic hit situations worldwide.


Subject(s)
COVID-19 , Antiviral Agents/pharmacology , COVID-19/drug therapy , Humans , Molecular Docking Simulation , Phytochemicals/chemistry , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , SARS-CoV-2 , Sennosides
3.
Appl Biochem Biotechnol ; 194(1): 291-301, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1748423

ABSTRACT

Corona virus pandemic outbreak also known as COVID-19 has created an imbalance in this world. Scientists have adopted the use of natural or alternative medicines which are consumed mostly as dietary supplements to boost the immune system as herbal remedies. India is famous for traditional medicinal formulations which includes 'Trikadu'-a combination of three acrids, namely Zingiber officinale, Piper nigrum and Piper longum which have antioxidant properties that boost our immune system hence acting as a strong preventive measure. In this study, AutoDock 4.0 was used to study interaction between the phytocompounds of Trikadu with RNA-dependent polymerase protein and enveloped protein of the SARS-CoV-2 virus. Analysis of the results showed that coumarin, coumaperine and bisdemethoxycurcumin showed strong bonding interactions with both the proteins. We can conclude that Trikadu has the potential molecules; hence, it can be incorporated in the diet to boost the immune system as a preventive measure against the virus.


Subject(s)
COVID-19/drug therapy , COVID-19/immunology , Phytotherapy , Plant Preparations/therapeutic use , SARS-CoV-2 , Antioxidants/isolation & purification , Antioxidants/therapeutic use , COVID-19/virology , Computer Simulation , Coronavirus RNA-Dependent RNA Polymerase/chemistry , Coronavirus RNA-Dependent RNA Polymerase/drug effects , Dietary Supplements , Ginger/chemistry , Humans , Immune System/drug effects , India , Ligands , Medicine, Traditional , Molecular Docking Simulation , Phytochemicals/chemistry , Phytochemicals/therapeutic use , Piper/chemistry , Piper nigrum/chemistry , Plant Preparations/isolation & purification , Plants, Medicinal/chemistry , SARS-CoV-2/chemistry , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/drug effects
4.
Molecules ; 27(2)2022 Jan 13.
Article in English | MEDLINE | ID: covidwho-1625268

ABSTRACT

The focus of this roadmap is to evaluate the possible efficacy of Artemisia herba-alba Asso. (Asteraceae) for the treatment of COVID-19 and some of its symptoms and several comorbidities using a combination of in silico (molecular docking) studies, reported ethnic uses, and pharmacological activity studies of this plant. In this exploratory study, we show that various phytochemicals from Artemisia herba-alba can be useful against COVID-19 (in silico studies) and for its associated comorbidities. COVID-19 is a new disease, so reports of any therapeutic treatments against it (traditional or conventional) are scanty. On the other hand, we demonstrate, using Artemisia herba-alba as an example, that through a proper search and identification of medicinal plant(s) and their phytochemicals identification using secondary data (published reports) on the plant's ethnic uses, phytochemical constituents, and pharmacological activities against COVID-19 comorbidities and symptoms coupled with the use of primary data obtained from in silico (molecular docking and molecular dynamics) studies on the binding of the selected plant's phytochemicals (such as: rutin, 4,5-di-O-caffeoylquinic acid, and schaftoside) with various vital components of SARS-CoV-2, it may be possible to rapidly identify plants that are suitable for further research regarding therapeutic use against COVID-19 and its associated symptoms and comorbidities.


Subject(s)
Artemisia/chemistry , COVID-19/drug therapy , Plant Extracts/chemistry , Plant Extracts/pharmacology , COVID-19/epidemiology , Comorbidity , Coronavirus 3C Proteases/chemistry , Ethnobotany/methods , Ligands , Molecular Docking Simulation , Molecular Dynamics Simulation , Phytochemicals/chemistry , Plants, Medicinal/chemistry
5.
Molecules ; 26(22)2021 Nov 10.
Article in English | MEDLINE | ID: covidwho-1512512

ABSTRACT

The novel coronavirus disease (COVID-19), the reason for worldwide pandemic, has already masked around 220 countries globally. This disease is induced by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). Arising environmental stress, increase in the oxidative stress level, weak immunity and lack of nutrition deteriorates the clinical status of the infected patients. Though several researches are at its peak for understanding and bringing forward effective therapeutics, yet there is no promising solution treating this disease directly. Medicinal plants and their active metabolites have always been promising in treating many clinical complications since time immemorial. Mother nature provides vivid chemical structures, which act multi-dimensionally all alone or synergistically in mitigating several diseases. Their unique antioxidant and anti-inflammatory activity with least side effects have made them more effective candidate for pharmacological studies. These medicinal plants inhibit attachment, encapsulation and replication of COVID-19 viruses by targeting various signaling molecules such as angiotensin converting enzyme-2, transmembrane serine protease 2, spike glycoprotein, main protease etc. This property is re-examined and its potency is now used to improve the existing global health crisis. This review is an attempt to focus various antiviral activities of various noteworthy medicinal plants. Moreover, its implications as prophylactic or preventive in various secondary complications including neurological, cardiovascular, acute kidney disease, liver disease are also pinpointed in the present review. This knowledge will help emphasis on the therapeutic developments for this novel coronavirus where it can be used as alone or in combination with the repositioned drugs to combat COVID-19.


Subject(s)
COVID-19/drug therapy , Drug Repositioning , Phytochemicals/therapeutic use , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/complications , COVID-19/pathology , COVID-19/virology , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/pathology , Humans , Phytochemicals/chemistry , Phytochemicals/metabolism , Phytochemicals/pharmacology , Plants, Medicinal/chemistry , Plants, Medicinal/metabolism , SARS-CoV-2/isolation & purification , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization/drug effects
6.
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
7.
Molecules ; 26(19)2021 Oct 08.
Article in English | MEDLINE | ID: covidwho-1463772

ABSTRACT

The naturally occurring saponins exhibit remarkable interfacial activity and also possess many biological activities linking to human health benefits, which make them particularly attractive as bifunctional building blocks for formulation of colloidal multiphase food systems. This review focuses on two commonly used food-grade saponins, Quillaja saponins (QS) and glycyrrhizic acid (GA), with the aim of clarifying the relationship between the structural features of saponin molecules and their subsequent self-assembly and interfacial properties. The recent applications of these two saponins in various colloidal multiphase systems, including liquid emulsions, gel emulsions, aqueous foams and complex emulsion foams, are then discussed. A particular emphasis is on the unique use of GA and GA nanofibrils as sole stabilizers for fabricating various multiphase food systems with many advanced qualities including simplicity, ultrastability, stimulability, structural viscoelasticity and processability. These natural saponin and saponin-based colloids are expected to be used as sustainable, plant-based ingredients for designing future foods, cosmetics and pharmaceuticals.


Subject(s)
Glycyrrhizic Acid/chemistry , Plants/chemistry , Quillaja Saponins/chemistry , Colloids/chemistry , Cosmetics/chemistry , Food Technology , Molecular Structure , Phytochemicals/chemistry
8.
Biomed Res Int ; 2021: 1636816, 2021.
Article in English | MEDLINE | ID: covidwho-1455769

ABSTRACT

Respiratory inflammation is caused by an air-mediated disease induced by polluted air, smoke, bacteria, and viruses. The COVID-19 pandemic is also a kind of respiratory disease, induced by a virus causing a serious effect on the lungs, bronchioles, and pharynges that results in oxygen deficiency. Extensive research has been conducted to find out the potent natural products that help to prevent, treat, and manage respiratory diseases. Traditionally, wider floras were reported to be used, such as Morus alba, Artemisia indica, Azadirachta indica, Calotropis gigantea, but only some of the potent compounds from some of the plants have been scientifically validated. Plant-derived natural products such as colchicine, zingerone, forsythiaside A, mangiferin, glycyrrhizin, curcumin, and many other compounds are found to have a promising effect on treating and managing respiratory inflammation. In this review, current clinically approved drugs along with the efficacy and side effects have been studied. The study also focuses on the traditional uses of medicinal plants on reducing respiratory complications and their bioactive phytoconstituents. The pharmacological evidence of lowering respiratory complications by plant-derived natural products has been critically studied with detailed mechanism and action. However, the scientific validation of such compounds requires clinical study and evidence on animal and human models to replace modern commercial medicine.


Subject(s)
COVID-19 , Pandemics , Phytochemicals/therapeutic use , Plant Extracts/therapeutic use , Plants, Medicinal/chemistry , SARS-CoV-2 , Animals , COVID-19/drug therapy , COVID-19/epidemiology , Humans , Inflammation/drug therapy , Inflammation/epidemiology , Phytochemicals/chemistry , Plant Extracts/chemistry
9.
Mini Rev Med Chem ; 22(3): 457-483, 2022.
Article in English | MEDLINE | ID: covidwho-1399062

ABSTRACT

Coronaviruses have caused worldwide outbreaks in different periods. SARS (severe acute respiratory syndrome) was the first emerged virus from this family, followed by MERS (Middle East respiratory syndrome) and SARS-CoV-2 (2019-nCoV or COVID 19), which is newly emerged. Many studies have been conducted on the application of chemical and natural drugs for treating these coronaviruses and they are mostly focused on inhibiting the proteases of viruses or blocking their protein receptors through binding to amino acid residues. Among many substances which are introduced to have an inhibitory effect against coronaviruses through the mentioned pathways, natural components are of specific interest. Secondary and primary metabolites from plants, are considered as potential drugs to have an inhibitory effect on coronaviruses. IC50 value (the concentration in which there is 50% loss in enzyme activity), molecular docking score and binding energy are parameters to understand the ability of metabolites to inhibit the specific virus. In this study we reviewed 154 papers on the effect of plant metabolites on different coronaviruses and data of their IC50 values, molecular docking scores and inhibition percentages are collected in tables. Secondary plant metabolites such as polyphenol, alkaloids, terpenoids, organosulfur compounds, saponins and saikosaponins, lectins, essential oil, and nicotianamine, and primary metabolites such as vitamins are included in this study.


Subject(s)
Antiviral Agents/pharmacology , Phytochemicals/pharmacology , SARS-CoV-2/drug effects , Antiviral Agents/chemistry , COVID-19/drug therapy , Humans , Inhibitory Concentration 50 , Molecular Docking Simulation , Phytochemicals/chemistry
10.
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
11.
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
12.
Int J Mol Sci ; 22(8)2021 Apr 09.
Article in English | MEDLINE | ID: covidwho-1298159

ABSTRACT

A comparative phytochemical study on the phenylethanoid glycoside (PhEG) composition of the underground organs of three Plantago species (P. lanceolata, P. major, and P. media) and that of the fruit wall and seed parts of Forsythia suspensa and F. europaea fruits was performed. The leaves of these Forsythia species and six cultivars of the hybrid F. × intermedia were also analyzed, demonstrating the tissue-specific accumulation and decomposition of PhEGs. Our analyses confirmed the significance of selected tissues as new and abundant sources of these valuable natural compounds. The optimized heat treatment of tissues containing high amounts of the PhEG plantamajoside (PM) or forsythoside A (FA), which was performed in distilled water, resulted in their characteristic isomerizations. In addition to PM and FA, high amounts of the isomerization products could also be isolated after heat treatment. The isomerization mechanisms were elucidated by molecular modeling, and the structures of PhEGs were identified by nuclear magnetic resonance spectroscopy (NMR) and high-resolution mass spectrometry (HR-MS) techniques, also confirming the possibility of discriminating regioisomeric PhEGs by tandem MS. The PhEGs showed no cytostatic activity in non-human primate Vero E6 cells, supporting their safe use as natural medicines and allowing their antiviral potency to be tested.


Subject(s)
Forsythia/chemistry , Glycosides/chemistry , Phytochemicals/chemistry , Plantago/chemistry , Animals , Chlorocebus aethiops , Chromatography, High Pressure Liquid , Forsythia/metabolism , Glycosides/metabolism , Glycosides/pharmacology , Isomerism , Molecular Conformation , Molecular Structure , Organ Specificity , Phytochemicals/metabolism , Phytochemicals/pharmacology , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plantago/metabolism , Structure-Activity Relationship , Vero Cells
13.
Molecules ; 26(13)2021 Jun 25.
Article in English | MEDLINE | ID: covidwho-1288961

ABSTRACT

A newly diagnosed coronavirus in 2019 (COVID-19) has affected all human activities since its discovery. Flavonoids commonly found in the human diet have attracted a lot of attention due to their remarkable biological activities. This paper provides a comprehensive review of the benefits of flavonoids in COVID-19 disease. Previously-reported effects of flavonoids on five RNA viruses with similar clinical manifestations and/or pharmacological treatments, including influenza, human immunodeficiency virus (HIV), severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and Ebola, were considered. Flavonoids act via direct antiviral properties, where they inhibit different stages of the virus infective cycle and indirect effects when they modulate host responses to viral infection and subsequent complications. Flavonoids have shown antiviral activity via inhibition of viral protease, RNA polymerase, and mRNA, virus replication, and infectivity. The compounds were also effective for the regulation of interferons, pro-inflammatory cytokines, and sub-cellular inflammatory pathways such as nuclear factor-κB and Jun N-terminal kinases. Baicalin, quercetin and its derivatives, hesperidin, and catechins are the most studied flavonoids in this regard. In conclusion, dietary flavonoids are promising treatment options against COVID-19 infection; however, future investigations are recommended to assess the antiviral properties of these compounds on this disease.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Flavonoids/pharmacology , Phytochemicals/pharmacology , SARS-CoV-2/drug effects , Animals , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Flavonoids/chemistry , Flavonoids/therapeutic use , Humans , Phytochemicals/chemistry , Phytochemicals/therapeutic use , Signal Transduction/drug effects
14.
Molecules ; 26(13)2021 Jun 25.
Article in English | MEDLINE | ID: covidwho-1288960

ABSTRACT

(1) Background: The COVID-19 pandemic lacks treatments; for this reason, the search for potential compounds against therapeutic targets is still necessary. Bioinformatics tools have allowed the rapid in silico screening of possible new metabolite candidates from natural resources or repurposing known ones. Thus, in this work, we aimed to select phytochemical candidates from Peruvian plants with antiviral potential against three therapeutical targets of SARS-CoV-2. (2) Methods: We applied in silico technics, such as virtual screening, molecular docking, molecular dynamics simulation, and MM/GBSA estimation. (3) Results: Rutin, a compound present in Peruvian native plants, showed affinity against three targets of SARS-CoV-2. The molecular dynamics simulation demonstrated the high stability of receptor-ligand systems during the time of the simulation. Our results showed that the Mpro-Rutin system exhibited higher binding free energy than PLpro-Rutin and N-Rutin systems through MM/GBSA analysis. (4) Conclusions: Our study provides insight on natural metabolites from Peruvian plants with therapeutical potential. We found Rutin as a potential candidate with multiple pharmacological properties against SARS-CoV-2.


Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Phytochemicals/chemistry , Phytochemicals/pharmacology , Plants/chemistry , Plants/metabolism , Asteraceae/chemistry , Asteraceae/metabolism , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus 3C Proteases/chemistry , Coronavirus Nucleocapsid Proteins/antagonists & inhibitors , Coronavirus Nucleocapsid Proteins/chemistry , Coronavirus Papain-Like Proteases/antagonists & inhibitors , Coronavirus Papain-Like Proteases/chemistry , Databases, Factual , Humans , Lepidium/chemistry , Lepidium/metabolism , Ligands , Molecular Docking Simulation , Molecular Dynamics Simulation , Peru , Phosphoproteins/antagonists & inhibitors , Phosphoproteins/chemistry , Rutin/chemistry , Rutin/pharmacology , SARS-CoV-2
15.
Plant J ; 107(5): 1299-1319, 2021 09.
Article in English | MEDLINE | ID: covidwho-1282039

ABSTRACT

Caffeoylquinic acids (CQAs) are specialized plant metabolites we encounter in our daily life. Humans consume CQAs in mg-to-gram quantities through dietary consumption of plant products. CQAs are considered beneficial for human health, mainly due to their anti-inflammatory and antioxidant properties. Recently, new biosynthetic pathways via a peroxidase-type p-coumaric acid 3-hydroxylase enzyme were discovered. More recently, a new GDSL lipase-like enzyme able to transform monoCQAs into diCQA was identified in Ipomoea batatas. CQAs were recently linked to memory improvement; they seem to be strong indirect antioxidants via Nrf2 activation. However, there is a prevalent confusion in the designation and nomenclature of different CQA isomers. Such inconsistencies are critical and complicate bioactivity assessment since different isomers differ in bioactivity and potency. A detailed explanation regarding the origin of such confusion is provided, and a recommendation to unify nomenclature is suggested. Furthermore, for studies on CQA bioactivity, plant-based laboratory animal diets contain CQAs, which makes it difficult to include proper control groups for comparison. Therefore, a synthetic diet free of CQAs is advised to avoid interferences since some CQAs may produce bioactivity even at nanomolar levels. Biotransformation of CQAs by gut microbiota, the discovery of new enzymatic biosynthetic and metabolic pathways, dietary assessment, and assessment of biological properties with potential for drug development are areas of active, ongoing research. This review is focused on the chemistry, biosynthesis, occurrence, analytical challenges, and bioactivity recently reported for mono-, di-, tri-, and tetraCQAs.


Subject(s)
Anti-Inflammatory Agents/chemistry , Antioxidants/chemistry , Cognitive Dysfunction/prevention & control , Neuroprotective Agents/chemistry , Phytochemicals/chemistry , Plants, Medicinal/chemistry , Quinic Acid/analogs & derivatives , Acyltransferases/genetics , Acyltransferases/metabolism , Animals , Anti-Inflammatory Agents/metabolism , Anti-Inflammatory Agents/pharmacology , Antioxidants/metabolism , Antioxidants/pharmacology , Biosynthetic Pathways , Brachypodium/enzymology , Dietary Supplements , Humans , Ipomoea batatas/enzymology , Mixed Function Oxygenases/genetics , Mixed Function Oxygenases/metabolism , Neuroprotective Agents/metabolism , Neuroprotective Agents/pharmacology , Phytochemicals/metabolism , Phytochemicals/pharmacology , Plant Proteins/genetics , Plant Proteins/metabolism , Quinic Acid/chemistry , Quinic Acid/metabolism , Quinic Acid/pharmacology , Terminology as Topic
16.
Mol Biotechnol ; 63(10): 898-908, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1279492

ABSTRACT

New pandemic infection of coronaviridae family virus spread to more than 210 countries with total infection of 1,136,851 and 62,955 (4.6%) deaths until 5th April 2020. Which stopped the regular cycle of humankind but the nature is consistently running. There is no micro molecule remedy found yet to restore the regular life of people. Hence, we decided to work on natural biophores against the COVID proteins. As a first step, major phytoconstituents of antiviral herbs like Leucas aspera, Morinda citrifolia, Azadirachta indica, Curcuma longa, Piper nigrum, Ocimum tenuiflorum, and Corallium rubrum collected and performed the lock and key analysis with major spike protein of COVID-19 to find the best fitting lead biophore using computational drug design platform. The results of protocol run showed, phytoconstituents of Morinda citrifolia and Leucas aspera were found lower binding energy range of - 55.18 to - 25.34 kcal/mol, respectively and compared with Hydroxychloroquine (HCQ) (- 24.29 kcal/mol) and Remdesivir (- 25.38 kcal/mol). The results conclude that, core skeletons chromen, anthracene 9, 11 dione and long-chain alkyl acids/ester-containing biophores showen high stable antagonistic affinity with S-protein. Which leads the breakdown of spike protein and ACE2 receptor complex formation and host mechanism of corono virus. In addition, the dynamic trajectory analysis confirmed the complete denaturation of spike protein by the molecule 4-(24-hydroxy-1-oxo-5-n-propyltetracosanyl)-phenol from Leucas aspera and stability of spike-ligand complex. These biophores will aid the researcher to fabricate new promising analogue and being recommended to assess its COVID-19 treatment.


Subject(s)
Antiviral Agents/chemistry , Phytochemicals/chemistry , Spike Glycoprotein, Coronavirus/chemistry , Antiviral Agents/pharmacology , COVID-19/drug therapy , COVID-19/virology , Catalytic Domain , Drug Design , Humans , Molecular Docking Simulation , Molecular Structure , Plants, Medicinal/chemistry , Protein Binding/drug effects , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/antagonists & inhibitors
17.
Phytother Res ; 35(6): 3262-3274, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1274778

ABSTRACT

SARS-CoV-2 has caused millions of infections and more than 700,000 deaths. Taking the urgent need to find new therapeutics for coronavirus disease 2019 (COVID-19), a dataset of plant-based natural compounds was selected for the screening of antiviral activity. The viral 3-chymotrypsin-like cysteine protease (Mpro, 3CLpro) was selected as the target. Molecular docking was performed on 2,845 phytochemicals to estimate the spatial affinity for the active sites of the enzyme. The ADMET screening was used for the pharmacological and physicochemical properties of the hit compounds. Nelfinavir and Lopinavir were used as control for binding energy comparison. The top 10 hits, based on the binding energy (Kcal/mol), were Ginkgolide M (-11.2), Mezerein (-11), Tubocurarine (-10.9), Gnidicin (-10.4), Glycobismine A (-10.4), Sciadopitysin Z-10.2), Gnididin (-9.2), Glycobismine A (-10.4), Sciadopitysin (-10.2), Gnididin (-9.20, Emetine (-8.7), Vitexin (-8.3), Calophyllolide (-8.3), and 6-(3,3-Dimethylallyl)galangin (-7.9). The binding energy for nelfinavir and lopinavir were - 9.1 and - 8.4, respectively. Interestingly, some of these natural products were previously shown to possess antiviral properties against various viruses, such as HIV, Zika, and Ebola viruses. Herein, we suggest several phytochemicals as the inhibitors of the main protease of SARS-CoV-2 that could be used in the fight against COVID-19.


Subject(s)
COVID-19/drug therapy , Phytochemicals/pharmacology , Protease Inhibitors/pharmacology , SARS-CoV-2/drug effects , Antiviral Agents/pharmacology , Humans , Molecular Docking Simulation , Peptide Hydrolases/drug effects , Phytochemicals/chemistry , Protease Inhibitors/chemistry
18.
Mol Divers ; 26(1): 429-442, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1265543

ABSTRACT

The SARS-CoV-2 helicase Nsp13 is a promising target for developing anti-COVID drugs. In the present study, we have identified potential natural product inhibitors of SARS-CoV-2 Nsp13 targeting the ATP-binding site using molecular docking and molecular dynamics (MD) simulations. MD simulation of the prepared crystal structure of SARS-CoV-2 Nsp13 was performed to generate an ensemble of structures of helicase Nsp13 capturing the conformational diversity of the ATP-binding site. A natural product library of more than 14,000 phytochemicals from Indian medicinal plants was used to perform virtual screening against the ensemble of Nsp13 structures. Subsequently, a two-stage filter, first based on protein-ligand docking binding energy value and second based on protein residues in the ligand-binding site and non-covalent interactions between the protein residues and the ligand in the best-docked pose, was used to identify 368 phytochemicals as potential inhibitors of SARS-CoV-2 helicase Nsp13. MD simulations of the top inhibitors complexed with protein were performed to confirm stable binding, and to compute MM-PBSA based binding energy. From among the 368 potential phytochemical inhibitors, the top identified potential inhibitors of SARS-CoV-2 helicase Nsp13 namely, Picrasidine M, (+)-Epiexcelsin, Isorhoeadine, Euphorbetin and Picrasidine N, can be taken up initially for experimental studies.


Subject(s)
COVID-19 , SARS-CoV-2 , Antiviral Agents/chemistry , COVID-19/drug therapy , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Phytochemicals/chemistry , Phytochemicals/pharmacology , Protease Inhibitors/pharmacology
19.
J Biomol Struct Dyn ; 40(7): 3155-3169, 2022 04.
Article in English | MEDLINE | ID: covidwho-1246547

ABSTRACT

SARS-CoV-2 cause fatal infection in 213 countries accounting for the death of millions of people globally. In the present study, phytochemicals from spices were assessed for their ability to interact with SARS-CoV-2 MPro. Structure based virtual screening was performed with 146 phytochemicals from spices using Autodock Vina. Phytochemicals with binding energy ≥ -8.0 kcal/mol were selected to understand their interaction with MPro. Virtual screening was further validated by performing molecular docking to generate favorable docked poses and the participation of important amino acid residues. Molecular dynamics simulation for the docked poses was performed to study thermodynamic properties of the protein, ligand and protein-ligand complexes. The finding shows that cinnamtannin B2 and cyanin showed favorable binding affinity values with SARS-CoV-2 MPro. The results are comparable in terms of docked poses, important amino acid participation and thermodynamic properties with the standard control drugs remdesivir, benazepril and hydroxychloroquine diphosphate. Prime MM-GBSA was employed for end-point binding energy calculation. Binding to domain I and II of MPro were mediated through the OH, SH, NH2 and non-polar side chain of amino acids. Cinnamtannin B2 and cyanin binds to MPro with many sub sites within the active site with RMSD and RMSF within 4 Å. The results computed using Prime MM-GBSA show that cinnamtannin B2 (-68.54940214 kcal/mol) and cyanin (-62.1902835 kcal/mol) have better binding affinity in comparison to hydroxychloroquine diphosphate (-54.00912412 kcal/mol) and benazepril (-53.70242369 kcal/mol). The results provide a basis for exploiting cinnamtannin B2 and cyanin as a starting point potential candidate for the development of drug against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.


Subject(s)
COVID-19 , Molecular Dynamics Simulation , COVID-19/drug therapy , Humans , Molecular Docking Simulation , Phytochemicals/chemistry , Phytochemicals/pharmacology , Protease Inhibitors/chemistry , SARS-CoV-2
20.
Biomed Res Int ; 2021: 6661191, 2021.
Article in English | MEDLINE | ID: covidwho-1241066

ABSTRACT

The recent COVID-19 pandemic has impacted nearly the whole world due to its high morbidity and mortality rate. Thus, scientists around the globe are working to find potent drugs and designing an effective vaccine against COVID-19. Phytochemicals from medicinal plants are known to have a long history for the treatment of various pathogens and infections; thus, keeping this in mind, this study was performed to explore the potential of different phytochemicals as candidate inhibitors of the HR1 domain in SARS-CoV-2 spike protein by using computer-aided drug discovery methods. Initially, the pharmacological assessment was performed to study the drug-likeness properties of the phytochemicals for their safe human administration. Suitable compounds were subjected to molecular docking to screen strongly binding phytochemicals with HR1 while the stability of ligand binding was analyzed using molecular dynamics simulations. Quantum computation-based density functional theory (DFT) analysis was constituted to analyze the reactivity of these compounds with the receptor. Through analysis, 108 phytochemicals passed the pharmacological assessment and upon docking of these 108 phytochemicals, 36 were screened passing a threshold of -8.5 kcal/mol. After analyzing stability and reactivity, 5 phytochemicals, i.e., SilybinC, Isopomiferin, Lycopene, SilydianinB, and Silydianin are identified as novel and potent candidates for the inhibition of HR1 domain in SARS-CoV-2 spike protein. Based on these results, it is concluded that these compounds can play an important role in the design and development of a drug against COVID-19, after an exhaustive in vitro and in vivo examination of these compounds, in future.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Phytochemicals/pharmacology , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Antiviral Agents/chemistry , Binding Sites , COVID-19/virology , Density Functional Theory , Drug Discovery , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Phytochemicals/chemistry , Protein Domains , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification
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