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1.
Molecules ; 26(24)2021 Dec 07.
Article in English | MEDLINE | ID: covidwho-1599069

ABSTRACT

It is a distinct pleasure for me to offer something in recognition of and tribute to Dr [...].


Subject(s)
Biological Products/chemical synthesis , Plants/chemistry , Biological Products/chemistry , History, 20th Century , History, 21st Century , Humans
2.
Bioorg Chem ; 117: 105460, 2021 12.
Article in English | MEDLINE | ID: covidwho-1487614

ABSTRACT

The current pneumonia outbreak, which began in early December 2019 near Wuhan City, Hubei Province, China, is caused by a novel corona virus (CoV) known as '2019-nCoV' or '2019 novel corona virus or COVID-19' by the World Health Organization (WHO). Vaccines are available to prevent corona virus contagious infection or to reduce the viral load in body but virus is continuously mutating itself to infect people at severity. In this critical scenario this review provide a compiled study for techniques and tools that can be used to treat corona virus infections and its variants by some modern techniques and natural products such as inhibitors, siRNA technique and plant based approaches. This review focuses on healthy treatment and strategies that can be used effectively to treat the disease globally by reducing the post COVID symptoms.


Subject(s)
Biological Products/chemistry , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/metabolism , Biological Products/metabolism , Biological Products/therapeutic use , COVID-19/drug therapy , COVID-19/pathology , COVID-19/virology , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus 3C Proteases/metabolism , Humans , Plants/chemistry , Plants/metabolism , RNA, Small Interfering/metabolism , RNA, Small Interfering/therapeutic use , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism
3.
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
4.
Int J Mol Sci ; 22(16)2021 Aug 20.
Article in English | MEDLINE | ID: covidwho-1374421

ABSTRACT

Polyphenols, such as flavonoids and phenolic acids, are a group of specialized metabolites in plants that largely aid in plant defense by deterring biotic stressors and alleviating abiotic stress. Polyphenols offer a wide range of medical applications, acting as preventative and active treatments for diseases such as cancers and diabetes. Recently, researchers have proposed that polyphenols may contribute to certain applications aimed at tackling challenges related to the COVID-19 pandemic. Understanding the beneficial impacts of phytochemicals, such as polyphenols, could potentially help prepare society for future pandemics. Thus far, most reviews have focused on polyphenols in cancer prevention and treatment. This review aims to provide a comprehensive discussion on the critical roles that polyphenols play in both plant chemical defense and human health based on the most recent studies while highlighting prospective avenues for future research, as well as the implications for phytochemical-based applications in both agricultural and medical fields.


Subject(s)
Plants/metabolism , Polyphenols/pharmacology , Polyphenols/therapeutic use , Animals , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/pharmacology , Antiviral Agents/pharmacology , Biological Availability , COVID-19/drug therapy , COVID-19/prevention & control , Flavonoids/pharmacology , Flavonoids/therapeutic use , Humans , Hydroxybenzoates/pharmacology , Hypoglycemic Agents/pharmacology , Neoplasms/drug therapy , Phytochemicals , Plants/chemistry , Polyphenols/metabolism , Prospective Studies , SARS-CoV-2/drug effects
5.
Brief Bioinform ; 22(2): 1402-1414, 2021 03 22.
Article in English | MEDLINE | ID: covidwho-1343661

ABSTRACT

The new coronavirus (SARS-CoV-2) halts the world economy and caused unbearable medical emergency due to high transmission rate and also no effective vaccine and drugs has been developed which brought the world pandemic situations. The main protease (Mpro) of SARS-CoV-2 may act as an effective target for drug development due to the conservation level. Herein, we have employed a rigorous literature review pipeline to enlist 3063 compounds from more than 200 plants from the Asian region. Therefore, the virtual screening procedure helps us to shortlist the total compounds into 19 based on their better binding energy. Moreover, the Prime MM-GBSA procedure screened the compound dataset further where curcumin, gartanin and robinetin had a score of (-59.439, -52.421 and - 47.544) kcal/mol, respectively. The top three ligands based on binding energy and MM-GBSA scores have most of the binding in the catalytic groove Cys145, His41, Met165, required for the target protein inhibition. The molecular dynamics simulation study confirms the docked complex rigidity and stability by exploring root mean square deviations, root mean square fluctuations, solvent accessible surface area, radius of gyration and hydrogen bond analysis from simulation trajectories. The post-molecular dynamics analysis also confirms the interactions of the curcumin, gartanin and robinetin in the similar binding pockets. Our computational drug designing approach may contribute to the development of drugs against SARS-CoV-2.


Subject(s)
COVID-19/virology , Plants/chemistry , Protease Inhibitors/metabolism , SARS-CoV-2/enzymology , Humans , Molecular Dynamics Simulation
6.
Molecules ; 26(13)2021 Jul 05.
Article in English | MEDLINE | ID: covidwho-1295889

ABSTRACT

COVID-19 is a pandemic disease caused by the SARS-CoV-2 virus, which is potentially fatal for vulnerable individuals. Disease management represents a challenge for many countries, given the shortage of medicines and hospital resources. The objective of this work was to review the medicinal plants, foods and natural products showing scientific evidence for host protection against various types of coronaviruses, with a focus on SARS-CoV-2. Natural products that mitigate the symptoms caused by various coronaviruses are also presented. Particular attention was placed on natural products that stabilize the Renin-Angiotensin-Aldosterone System (RAAS), which has been associated with the entry of the SARS-CoV-2 into human cells.


Subject(s)
Biological Products/pharmacology , Coronavirus/drug effects , Phytotherapy/methods , Plant Extracts/pharmacology , SARS-CoV-2/drug effects , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Biological Products/metabolism , COVID-19/drug therapy , COVID-19/virology , Humans , Pandemics , Plant Extracts/metabolism , Plants/chemistry , Renin-Angiotensin System/drug effects
7.
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
8.
Cells ; 10(7)2021 06 28.
Article in English | MEDLINE | ID: covidwho-1288809

ABSTRACT

Betacoronaviruses, responsible for the "Severe Acute Respiratory Syndrome" (SARS) and the "Middle East Respiratory Syndrome" (MERS), use the spikes protruding from the virion envelope to attach and subsequently infect the host cells. The coronavirus spike (S) proteins contain receptor binding domains (RBD), allowing the specific recognition of either the dipeptidyl peptidase CD23 (MERS-CoV) or the angiotensin-converting enzyme ACE2 (SARS-Cov, SARS-CoV-2) host cell receptors. The heavily glycosylated S protein includes both complex and high-mannose type N-glycans that are well exposed at the surface of the spikes. A detailed analysis of the carbohydrate-binding specificity of mannose-binding lectins from plants, algae, fungi, and bacteria, revealed that, depending on their origin, they preferentially recognize either complex type N-glycans, or high-mannose type N-glycans. Since both complex and high-mannose glycans substantially decorate the S proteins, mannose-specific lectins are potentially useful glycan probes for targeting the SARS-CoV, MERS-CoV, and SARS-CoV-2 virions. Mannose-binding legume lectins, like pea lectin, and monocot mannose-binding lectins, like snowdrop lectin or the algal lectin griffithsin, which specifically recognize complex N-glycans and high-mannose glycans, respectively, are particularly adapted for targeting coronaviruses. The biomedical prospects of targeting coronaviruses with mannose-specific lectins are wide-ranging including detection, immobilization, prevention, and control of coronavirus infection.


Subject(s)
Lectins/pharmacology , Middle East Respiratory Syndrome Coronavirus/metabolism , SARS Virus/metabolism , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , COVID-19/drug therapy , COVID-19/virology , Cyanobacteria/chemistry , Drug Delivery Systems/methods , Fungi/chemistry , Humans , Lectins/isolation & purification , Lectins/therapeutic use , Middle East Respiratory Syndrome Coronavirus/physiology , Plants/chemistry , Protein Binding , SARS Virus/physiology , SARS-CoV-2/physiology , Species Specificity , Virus Internalization/drug effects
10.
Molecules ; 25(22)2020 Nov 11.
Article in English | MEDLINE | ID: covidwho-917015

ABSTRACT

Flavonoids are phytochemical compounds present in many plants, fruits, vegetables, and leaves, with potential applications in medicinal chemistry. Flavonoids possess a number of medicinal benefits, including anticancer, antioxidant, anti-inflammatory, and antiviral properties. They also have neuroprotective and cardio-protective effects. These biological activities depend upon the type of flavonoid, its (possible) mode of action, and its bioavailability. These cost-effective medicinal components have significant biological activities, and their effectiveness has been proved for a variety of diseases. The most recent work is focused on their isolation, synthesis of their analogs, and their effects on human health using a variety of techniques and animal models. Thousands of flavonoids have been successfully isolated, and this number increases steadily. We have therefore made an effort to summarize the isolated flavonoids with useful activities in order to gain a better understanding of their effects on human health.


Subject(s)
Flavonoids/chemistry , Flavonoids/pharmacology , Alzheimer Disease/drug therapy , Alzheimer Disease/prevention & control , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Antimalarials/chemistry , Antimalarials/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Cardiovascular System/drug effects , Flavonoids/economics , Humans , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Mice , Nervous System/drug effects , Neurons/drug effects , Neuroprotective Agents/chemistry , Neuroprotective Agents/pharmacology , Plant Extracts/pharmacology , Plant Leaves/chemistry , Plants/chemistry , Polyphenols/chemistry , Polyphenols/pharmacology , Quercetin/chemistry , Quercetin/pharmacology , Rats , Rats, Sprague-Dawley , Rats, Wistar , Stroke/drug therapy , Stroke/prevention & control
11.
Int J Biol Macromol ; 182: 743-749, 2021 Jul 01.
Article in English | MEDLINE | ID: covidwho-1163841

ABSTRACT

The development of high-end targeted drugs and vaccines against modern pandemic infections, such as COVID-19, can take a too long time that lets the epidemic spin up and harms society. However, the countermeasures must be applied against the infection in this period until the targeted drugs became available. In this regard, the non-specific, broad-spectrum anti-viral means could be considered as a compromise allowing overcoming the period of trial. One way to enhance the ability to resist the infection is to activate the nonspecific immunity using a suitable driving-up agent, such as plant polysaccharides, particularly our drug Panavir isolated from the potato shoots. Earlier, we have shown the noticeable anti-viral and anti-bacterial activity of Panavir. Here we demonstrate the pro-inflammation activity of Panavir, which four-to-eight times intensified the ATP and MIF secretion by HL-60 cells. This effect was mediated by the active phagocytosis of the Panavir particles by the cells. We hypothesized the physiological basis of the Panavir proinflammatory activity is mediated by the indol-containing compounds (auxins) present in Panavir and acting as a plant analog of serotonin.


Subject(s)
Antiviral Agents , COVID-19/drug therapy , Drug Carriers , Nanoparticles , Plants/chemistry , Polysaccharides , Probucol , Adolescent , Adult , Antiviral Agents/chemistry , Antiviral Agents/pharmacokinetics , Antiviral Agents/pharmacology , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Drug Carriers/pharmacology , HL-60 Cells , Humans , Male , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Phagocytosis/drug effects , Polysaccharides/chemistry , Polysaccharides/pharmacology , Probucol/chemistry , Probucol/pharmacokinetics , Probucol/pharmacology
12.
Molecules ; 26(7)2021 Mar 30.
Article in English | MEDLINE | ID: covidwho-1160340

ABSTRACT

The main protease (Mpro) is a major protease having an important role in viral replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that caused the pandemic of 2020. Here, active Mpro was obtained as a 34.5 kDa protein by overexpression in E. coli BL21 (DE3). The optimal pH and temperature of Mpro were 7.5 and 37 °C, respectively. Mpro displayed a Km value of 16 µM with Dabcyl-KTSAVLQ↓SGFRKME-Edans. Black garlic extract and 49 polyphenols were studied for their inhibitory effects on purified Mpro. The IC50 values were 137 µg/mL for black garlic extract and 9-197 µM for 15 polyphenols. The mixtures of tannic acid with puerarin, daidzein, and/or myricetin enhanced the inhibitory effects on Mpro. The structure-activity relationship of these polyphenols revealed that the hydroxyl group in C3', C4', C5' in the B-ring, C3 in the C-ring, C7 in A-ring, the double bond between C2 and C3 in the C-ring, and glycosylation at C8 in the A-ring contributed to inhibitory effects of flavonoids on Mpro.


Subject(s)
Coronavirus 3C Proteases/antagonists & inhibitors , Polyphenols/chemistry , Polyphenols/pharmacology , Protease Inhibitors/pharmacology , Coronavirus 3C Proteases/genetics , Coronavirus 3C Proteases/metabolism , Dimethyl Sulfoxide/pharmacology , Drug Synergism , Garlic/chemistry , Hydrogen-Ion Concentration , Plant Extracts/pharmacology , Plants/chemistry , Protease Inhibitors/chemistry , Structure-Activity Relationship , Temperature
13.
Expert Rev Clin Pharmacol ; 14(5): 623-633, 2021 May.
Article in English | MEDLINE | ID: covidwho-1132334

ABSTRACT

INTRODUCTION: The COVID-19 global pandemic is a public health emergency due to its high virulence and mortality. Many vaccine development studies at clinical trials are currently conducted to combat SARS-CoV-2. Plants are a rich source of phytochemicals with different biological activities, including antiviral activities, which are the focus of many studies. AREAS COVERED: This review shows compounds of traditional plants listed on RENISUS list have therapeutic properties against SARS-CoV-2 targets. EXPERT OPINION: The rise of new variants, more pathogenic and virulent, impacts in the increase of mortality from SARS-CoV-2 infection, and thus, the control of the outbreaks of disease remains a global challenge. Other's drug and vaccines development is an essential element in controlling SARS-COV-2. Therefore, it is imperative that approach to tackle this pandemic has to be solidly evidence-informed. It should be noticed that the immune system does play critical roles in fighting viruses. Studies show that T cells levels decreased continuously as the disease progressed. T cell-mediated cellular immune response, probably by immunological memory, is essential for direct virus eradication after infection whilst B cells functions in producing antibodies that neutralize virus.But, have distinct patterns of T cell response exist in different patients, suggesting the possibility of distinct clinical approaches. Efforts are concentrated to elucidate the underlying immunological mechanisms in SARS-CoV-2 pathogenesis and progression for better design of diagnostic, therapeutic and preventive strategies. We seek to identify biomolecules with the potential to act in biomarkers that predict how severe the disease can get. But it is important to warn that the plants that produce the compounds mentioned here should not be used without a physician prescription. Finally, we speculate that these compounds may eventually attract the attention of physicians and researchers to perform tests in specific contexts of SARS-CoV-2 infection, and if they show positive results, be tested in Clinical trials.


Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Biological Products/pharmacology , Plants/chemistry , SARS-CoV-2/drug effects , Biological Products/chemistry , Phytotherapy , Plant Preparations/chemistry , Plant Preparations/pharmacology
14.
Int J Mol Sci ; 22(5)2021 Mar 03.
Article in English | MEDLINE | ID: covidwho-1129730

ABSTRACT

According to the World Health Organization, cardiovascular diseases are the main cause of death worldwide. They may be caused by various factors or combinations of factors. Frequently, endothelial dysfunction is involved in either development of the disorder or results from it. On the other hand, the endothelium may be disordered for other reasons, e.g., due to infection, such as COVID-19. The understanding of the role and significance of the endothelium in the body has changed significantly over time-from a simple physical barrier to a complex system encompassing local and systemic regulation of numerous processes in the body. Endothelium disorders may arise from impairment of one or more signaling pathways affecting dilator or constrictor activity, including nitric oxide-cyclic guanosine monophosphate activation, prostacyclin-cyclic adenosine monophosphate activation, phosphodiesterase inhibition, and potassium channel activation or intracellular calcium level inhibition. In this review, plants are summarized as sources of biologically active substances affecting the endothelium. This paper compares individual substances and mechanisms that are known to affect the endothelium, and which subsequently may cause the development of cardiovascular disorders.


Subject(s)
Endothelium, Vascular/drug effects , Endothelium, Vascular/physiology , Plants/chemistry , Secondary Metabolism , Endothelium, Vascular/cytology , Humans , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plants/metabolism , Vasodilation/drug effects , Vasodilation/physiology , Vasodilator Agents/chemistry , Vasodilator Agents/pharmacology
15.
Mar Drugs ; 19(2)2021 Jan 27.
Article in English | MEDLINE | ID: covidwho-1050622

ABSTRACT

Inorganic polyphosphate (polyP) is a widely distributed polymer found from bacteria to animals, including marine species. This polymer exhibits morphogenetic as well as antiviral activity and releases metabolic energy after enzymatic hydrolysis also in human cells. In the pathogenesis of the coronavirus disease 2019 (COVID-19), the platelets are at the frontline of this syndrome. Platelets release a set of molecules, among them polyP. In addition, the production of airway mucus, the first line of body defense, is impaired in those patients. Therefore, in this study, amorphous nanoparticles of the magnesium salt of polyP (Mg-polyP-NP), matching the size of the coronavirus SARS-CoV-2, were prepared and loaded with the secondary plant metabolite quercetin or with dexamethasone to study their effects on the respiratory epithelium using human alveolar basal epithelial A549 cells as a model. The results revealed that both compounds embedded into the polyP nanoparticles significantly increased the steady-state-expression of the MUC5AC gene. This mucin species is the major mucus glycoprotein present in the secreted gel-forming mucus. The level of gene expression caused by quercetin or with dexamethasone, if caged into polyP NP, is significantly higher compared to the individual drugs alone. Both quercetin and dexamethasone did not impair the growth-supporting effect of polyP on A549 cells even at concentrations of quercetin which are cytotoxic for the cells. A possible mechanism of the effects of the two drugs together with polyP on mucin expression is proposed based on the scavenging of free oxygen species and the generation of ADP/ATP from the polyP, which is needed for the organization of the protective mucin-based mucus layer.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Dexamethasone/pharmacology , Mucin 5AC/biosynthesis , Mucin 5AC/drug effects , Quercetin/pharmacology , A549 Cells , Anti-Inflammatory Agents/chemistry , Antioxidants/chemistry , COVID-19 , Dexamethasone/chemistry , Free Radical Scavengers/pharmacology , Gene Expression Regulation/drug effects , Humans , Magnesium/chemistry , Mucin 5AC/genetics , Mucins/biosynthesis , Mucins/chemistry , Nanoparticles , Particle Size , Plants/chemistry , Polyphosphates/chemistry , Quercetin/chemistry , Reactive Oxygen Species
16.
Sci Rep ; 10(1): 20584, 2020 11 25.
Article in English | MEDLINE | ID: covidwho-947551

ABSTRACT

Plants are endowed with a large pool of structurally diverse small molecules known as secondary metabolites. The present study aims to virtually screen these plant secondary metabolites (PSM) for their possible anti-SARS-CoV-2 properties targeting four proteins/ enzymes which govern viral pathogenesis. Results of molecular docking with 4,704 ligands against four target proteins, and data analysis revealed a unique pattern of structurally similar PSM interacting with the target proteins. Among the top-ranked PSM which recorded lower binding energy (BE), > 50% were triterpenoids which interacted strongly with viral spike protein-receptor binding domain, > 32% molecules which showed better interaction with the active site of human transmembrane serine protease were belongs to flavonoids and their glycosides, > 16% of flavonol glycosides and > 16% anthocyanidins recorded lower BE against active site of viral main protease and > 13% flavonol glycoside strongly interacted with active site of viral RNA-dependent RNA polymerase. The primary concern about these PSM is their bioavailability. However, several PSM recorded higher bioavailability score and found fulfilling most of the drug-likeness characters as per Lipinski's rule (Coagulin K, Kamalachalcone C, Ginkgetin, Isoginkgetin, 3,3'-Biplumbagin, Chrysophanein, Aromoline, etc.). Natural occurrence, bio-transformation, bioavailability of selected PSM and their interaction with the target site of selected proteins were discussed in detail. Present study provides a platform for researchers to explore the possible use of selected PSM to prevent/ cure the COVID-19 by subjecting them for thorough in vitro and in vivo evaluation for the capabilities to interfering with the process of viral host cell recognition, entry and replication.


Subject(s)
Antiviral Agents/chemistry , COVID-19/virology , Computer Simulation , Plant Extracts/chemistry , Plants/metabolism , SARS-CoV-2/drug effects , Secondary Metabolism , Catalytic Domain , Coronavirus M Proteins/chemistry , Drug Evaluation, Preclinical/methods , Flavonoids/chemistry , Humans , Molecular Docking Simulation , Plant Extracts/pharmacology , Plants/chemistry , Protein Binding , RNA-Dependent RNA Polymerase/chemistry , SARS-CoV-2/enzymology , Serine Endopeptidases/chemistry , Spike Glycoprotein, Coronavirus/chemistry
17.
Biomolecules ; 10(11)2020 11 02.
Article in English | MEDLINE | ID: covidwho-921178

ABSTRACT

Plants have been used as drugs to treat human disease for centuries. Ursonic acid (UNA) is a naturally occurring pentacyclic triterpenoid extracted from certain medicinal herbs such as Ziziphus jujuba. Since the pharmacological effects and associated mechanisms of UNA are not well-known, in this work, we attempt to introduce the therapeutic potential of UNA with a comparison to ursolic acid (ULA), a well-known secondary metabolite, for beneficial effects. UNA has a keto group at the C-3 position, which may provide a critical difference for the varied biological activities between UNA and ULA. Several studies previously showed that UNA exerts pharmaceutical effects similar to, or stronger than, ULA, with UNA significantly decreasing the survival and proliferation of various types of cancer cells. UNA has potential to exert inhibitory effects in parasitic protozoa that cause several tropical diseases. UNA also exerts other potential effects, including antihyperglycemic, anti-inflammatory, antiviral, and antioxidant activities. Of note, a recent study highlighted the suppressive potential of UNA against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Molecular modifications of UNA may enhance bioavailability, which is crucial for in vivo and clinical studies. In conclusion, UNA has promising potential to be developed in anticancer and antiprotozoan pharmaceuticals. In-depth investigations may increase the possibility of UNA being developed as a novel reagent for chemotherapy.


Subject(s)
Antiviral Agents/pharmacology , Triterpenes/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/pharmacology , Antiviral Agents/chemistry , Betacoronavirus/drug effects , Betacoronavirus/physiology , Humans , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Plants/chemistry , SARS-CoV-2 , Triterpenes/chemistry , Triterpenes/metabolism
18.
Genomics ; 112(6): 4322-4331, 2020 11.
Article in English | MEDLINE | ID: covidwho-701714

ABSTRACT

COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is devastative to the humankind for which neither vaccines nor precise therapeutic molecules for treatment are identified. The search for new drugs and repurposing of existing drugs are being performed; however, at the same time, research on plants to identify novel therapeutic compounds or testing the existing ones is progressing at a slower phase. In this context, genomics and biotechnology offer various tools and strategies to manipulate plants for producing those complex biopharmaceutical products. This review enumerates the scope for research on plant-based molecules for their potential application in treating SARS-CoV-2 infection. Strategies to edit gene and genome, overexpression and silencing approaches, and molecular breeding for producing target biomolecules in the plant system are discussed in detail. Altogether, the present review provides a roadmap for expediting research on using plants as a novel source of active biomolecules having therapeutic applications.


Subject(s)
Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Genomics/methods , Plants/chemistry , Antiviral Agents/chemistry , COVID-19/drug therapy , Gene Editing , Humans , Plants/genetics , Plants/metabolism , Plants, Genetically Modified
19.
Acta Pharmacol Sin ; 41(9): 1178-1196, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-549299

ABSTRACT

ß-Sitosterol (24-ethyl-5-cholestene-3-ol) is a common phytosterol Chinese medical plants that has been shown to possess antioxidant and anti-inflammatory activity. In this study we investigated the effects of ß-sitosterol on influenza virus-induced inflammation and acute lung injury and the molecular mechanisms. We demonstrate that ß-sitosterol (150-450 µg/mL) dose-dependently suppresses inflammatory response through NF-κB and p38 mitogen-activated protein kinase (MAPK) signaling in influenza A virus (IAV)-infected cells, which was accompanied by decreased induction of interferons (IFNs) (including Type I and III IFN). Furthermore, we revealed that the anti-inflammatory effect of ß-sitosterol resulted from its inhibitory effect on retinoic acid-inducible gene I (RIG-I) signaling, led to decreased STAT1 signaling, thus affecting the transcriptional activity of ISGF3 (interferon-stimulated gene factor 3) complexes and resulting in abrogation of the IAV-induced proinflammatory amplification effect in IFN-sensitized cells. Moreover, ß-sitosterol treatment attenuated RIG-I-mediated apoptotic injury of alveolar epithelial cells (AEC) via downregulation of pro-apoptotic factors. In a mouse model of influenza, pre-administration of ß-sitosterol (50, 200 mg·kg-1·d-1, i.g., for 2 days) dose-dependently ameliorated IAV-mediated recruitment of pathogenic cytotoxic T cells and immune dysregulation. In addition, pre-administration of ß-sitosterol protected mice from lethal IAV infection. Our data suggest that ß-sitosterol blocks the immune response mediated by RIG-I signaling and deleterious IFN production, providing a potential benefit for the treatment of influenza.


Subject(s)
Acute Lung Injury/drug therapy , Antiviral Agents/therapeutic use , DEAD Box Protein 58/metabolism , Inflammation/drug therapy , Signal Transduction/drug effects , Sitosterols/therapeutic use , A549 Cells , Acute Lung Injury/pathology , Acute Lung Injury/virology , Animals , Antiviral Agents/analysis , Apoptosis/drug effects , Dogs , Female , HEK293 Cells , Humans , Inflammation/pathology , Inflammation/virology , Influenza A Virus, H1N1 Subtype/drug effects , Interferon Type I/metabolism , Interferons/metabolism , Lung/pathology , Madin Darby Canine Kidney Cells , Mice, Inbred BALB C , Plants/chemistry , STAT1 Transcription Factor/metabolism , Sitosterols/analysis
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