Antifungal Activity and Potential Action Mechanism of Allicin against Trichosporon asahii.

Trichosporon asahii is an emerging opportunistic pathogen that causes potentially fatal disseminated trichosporonosis. The global prevalence of coronavirus disease 2019 (COVID-19) poses an increasing fungal infection burden caused by T. asahii. Allicin is the main biologically active component with broad-spectrum antimicrobial activity in garlic. In this study, we performed an in-depth analysis of the antifungal characteristics of allicin against T. asahii based on physiological, cytological, and transcriptomic assessments. In vitro, allicin inhibited the growth of T. asahii planktonic cells and biofilm cells significantly. In vivo, allicin improved the mean survival time of mice with systemic trichosporonosis and reduced tissue fungal burden. Electron microscopy observations clearly demonstrated damage to T. asahii cell morphology and ultrastructure caused by allicin. Furthermore, allicin increased intracellular reactive oxygen species (ROS) accumulation, leading to oxidative stress damage in T. asahii cells. Transcriptome analysis showed that allicin treatment disturbed the biosynthesis of cell membrane and cell wall, glucose catabolism, and oxidative stress. The overexpression of multiple antioxidant enzymes and transporters may also place an additional burden on cells, causing them to collapse. Our findings shed new light on the potential of allicin as an alternative treatment strategy for trichosporonosis. IMPORTANCE Systemic infection caused by T. asahii has recently been recognized as an important cause of mortality in hospitalized COVID-19 patients. Invasive trichosporonosis remains a significant challenge for clinicians, due to the limited therapeutic options. The present work suggests that allicin holds great potential as a therapeutic candidate for T. asahii infection. Allicin demonstrated potent in vitro antifungal activity and potential in vivo protective effects. In addition, transcriptome sequencing provided valuable insights into the antifungal effects of allicin.

Scientific Evaluation of the Remedies Used in Turkish Folk Medicine to Treat Possible Viral Infections

Background: Plants, with their rich phytochemical treasury, are one of the main sources of drug development. However, a randomized search on plant sources for the discovery of phyto-chemicals with specified pharmacological activity is expensive and tedious. Therefore, it is logical to constrain the sources to increase success. In the recent four decades, the importance of traditional information has been recognized by the scientific community. Consequently, interest in field sur-veys for the documentation of traditional worldwide medicines has significantly increased. Method(s): Infectious diseases induced by pathogenic bacteria, fungi, or viruses have been one of the most common health problems for the public, for which traditional remedies have been practiced. Since laypeople could not distinguish the microbial origin of the infection, the remedies used for treatment could not be delineated. The aim of this study was first to search the plants used in Turkish folk medicine for such infectious diseases. The second step was to find scientific evidence in the online databases for the frequently quoted plants whether they may have potential activity against virus replication. Result(s): A reference survey on the most frequently quoted plants revealed that 16 out of 17 were shown to possess virucide or inhibitory effects on the replication of various viruses. Conclusion(s): Since each virus type may have a different viral replication pattern, further detailed in-vestigations should be carried out to reveal their exact antiviral potentials.Copyright © 2023 Bentham Science Publishers.

Screening of Natural Antivirals Against the COVID-19 Pandemic-A Compilation of Updates

Coronavirus disease 2019 (COVID-19), named by WHO, is a real public health disaster of the third millennium. This highly contagious viral disease has infected the world population and is now a global pandemic. This acute respiratory distress syndrome (ARDS) has severe complica-tions like pneumonitis, respiratory failure, shock, multiorgan failure, and death. Well-defined FDA-approved synthetic is not yet available. Case management strategies like lockdown, use of masks and sanitizers, social distancing, and repurposing of antiviral drugs were initially undertaken to cope with this pandemic. Different broad-spectrum antiviral drugs are being repurposed as one of the treatment modalities. The global vaccination programme with the newly launched COVID-19 vac-cines, Covishield, covaxin, sputnik V, etc., is an ongoing process. Simultaneously, significant research is being carried out in search of natural antivirals and evaluating the potency of food bioac-tives to aid naturistic protection against the coronavirus. This mini-review has compiled the latest updates on the screening and evidence-based mechanistic evaluation of phytochemicals and food bioactives as non-pharmacological adjuvant aid in COVID pandemics.Copyright © 2023 Bentham Science Publishers.

Molecular Screening of Bioactive Compounds of Garlic for Therapeutic Effects against COVID-19.

An outbreak of pneumonia occurred on December 2019 in Wuhan, China, which caused a serious public health emergency by spreading around the globe. Globally, natural products are being focused on more than synthetic ones. So, keeping that in view, the current study was conducted to discover potential antiviral compounds from Allium sativum. Twenty-five phytocompounds of this plant were selected from the literature and databases including 3-(Allylsulphinyl)-L-alanine, Allicin, Diallyl sulfide, Diallyl disulfide, Diallyl trisulfide, Glutathione, L-Cysteine, S-allyl-mercapto-glutathione, Quercetin, Myricetin, Thiocysteine, Gamma-glutamyl-Lcysteine, Gamma-glutamylallyl-cysteine, Fructan, Lauricacid, Linoleicacid, Allixin, Ajoene, Diazinon Kaempferol, Levamisole, Caffeicacid, Ethyl linoleate, Scutellarein, and S-allylcysteine methyl-ester. Virtual screening of these selected ligands was carried out against drug target 3CL protease by CB-dock. Pharmacokinetic and pharmacodynamic properties defined the final destiny of compounds as drug or non-drug molecules. The best five compounds screened were Allicin, Diallyl Sulfide, Diallyl Disulfide, Diallyl Trisulfide, Ajoene, and Levamisole, which showed themselves as hit compounds. Further refining by screening filters represented Levamisole as a lead compound. All the interaction visualization analysis studies were performed using the PyMol molecular visualization tool and LigPlot+. Conclusively, Levamisole was screened as a likely antiviral compound which might be a drug candidate to treat SARS-CoV-2 in the future. Nevertheless, further research needs to be carried out to study their potential medicinal use.

The Possible Role of Allicin in Ameliorating Azithromycin Induced Cardiotoxicity in Adult Male Albino Rat: A Histological and Immunohistochemical Study

Introduction: Azithromycin (AZ) is a broad-spectrum macrolide that is incorporated in the treatment of various infectious diseases, and recently enlisted in the protocol of Covid-19 management. Allicin is a classical garlic extraction with cardioprotective, antioxidant, anti-inflammatory, and anti-apoptotic properties. Aim of the Work: To evaluate the cardiotoxic effect of AZ and evaluate the possible protective effect of Allicin against AZ cardiotoxicity using various histological and immunohistochemical techniques. Materials and Methods: Forty adult male albino rats were randomly divided into four main groups: group-I acted as a control group, group-II was given Allicin (20 mg/kg/day) orally for consecutive 14 days, group-III was given AZ (30 mg/kg/ day) orally for consecutive 14 days and group-IV was given both AZ and Allicin in the same doses for consecutive 14 days. The cardiac specimens were processed for different histological and immunohistochemical techniques. Morphometrical and statistical studies were also done. Results: Azithromycin induced several myocardial changes in the form of focal areas of destruction of cardiac muscle fibers, darkly stained pyknotic nuclei and cytoplasmic vacuoles. Wavy muscle fibers, widening of the intercellular spaces, mononuclear cellular infiltration, fatty infiltration and hemorrhage were obvious. Dilated and congested blood vessels were also noticed. A significant increase in the mean area percentage of both Masson and α-SMA immunoreactivity was detected while a significant decrease in the mean area percentage of Bcl-2 was demonstrated. In contrast, most of the histological changes disappeared by Allicin co-treatment except in few localized areas. Conclusion: Azithromycin induced several destructive changes in cardiac muscle fibers. Allicin had a potent ameliorative role in prevention of cardiotoxicity induced by AZ. © 2022. All rights served.

Outlook of Covid-19 Curing through Structural and Electronic Properties of Natural Drugs

Humans and multiple species of animals must be infected by coronaviruses (positive-stranded RNA viruses) through enteric, respiratory, and central nervous system sickness with attractive targets for designing anti-Covid-19 conjunction. In this work, it has been investigated the compounds of luteolin-7-glucoside, curcumin, epicatechin-gallate, allicin, and zingerol as probable anti-pandemic Covid-19 receptors derived from medicinal plants. Anti-Covid-19 through the hydrogen bonding using the physicochemical features consisting of thermodynamic parameters, nuclear magnetic resonance analysis, and IR characteristics, of luteolin-7-glucoside, curcumin, epicatechin-gallate, allicin, and zingerol compounds binded to the fragment of Tyrosine-Methionine-Histidine as the selective area of the Covid-19, IR frequency and intensity of various normal modes of these structures have been estimated. The theoretical calculations were accomplished at different steps of theory to achieve the more accurate equilibrium geometrical consequences, and IR spectral analysis for each of the complex drugs of O-terminal or N-terminal auto-cleavage substrate were approved to clear the structural flexibility and substrate attaching of seven medicinal plants bonded to the active site of Covid-19 molecule. Comparing these compounds with two configurations prepares a new outlook for the design of substrate-based anti-targeting of Covid-19. This indicates a feasible model for designing a wide spectrum of anti-Covid-19 drugs. The compounds-based energy minimization of these materials has resulted in two more effectual lead compounds, N and O atoms, forming the hydrogen bonding (H-bonding) with potent anti-Covid-19. Finally, two medicinal ingredients of allicin, curcumin, luteolin-7-glucoside, and zingerol bonded to TMH have been directed to a Monte Carlo (MC) simulation and UV-Visible for estimating the absorbance of luteolin-7-glucoside, and epicatechin-gallate. © 2022 by the authors.

Allicin as a Volatile or Nebulisable Antimycotic for the Treatment of Pulmonary Mycoses: In Vitro Studies Using a Lung Flow Test Rig.

Fungal infections of the lung are an increasing problem worldwide and the search for novel therapeutic agents is a current challenge due to emerging resistance to current antimycotics. The volatile defence substance allicin is formed naturally by freshly injured garlic plants and exhibits broad antimicrobial potency. Chemically synthesised allicin was active against selected fungi upon direct contact and via the gas phase at comparable concentrations to the pharmaceutically used antimycotic amphotericin B. We investigated the suppression of fungal growth by allicin vapour and aerosols in vitro in a test rig at air flow conditions mimicking the human lung. The effect of allicin via the gas phase was enhanced by ethanol. Our results suggest that allicin is a potential candidate for development for use in antifungal therapy for lung and upper respiratory tract infections.

Ayurvedic antiviral agents: Overview of medicinal plants perspective

In recent years, it has been reported that many herbal plants contain antiviral agents which combat a human disease that is caused by pathogenic viruses. The natural products which are obtained from plants as antiviral agents against viruses have gone through researches to check the efficacy and potentials of the herbal products in the prevention of viral disorders. On the basis of randomized controlled studies and in-vivo studies, and in-vitro studies, some agents are utilized all across the globe. Progressively numerous studies on therapy of antivirals have been increased. Though, efficacy remains disputable for antiviral drugs that are employed for viral disorders. The viral diseases are challenging for the health of people around the world cause significant increase in mortality and enhance crises. There are many synthetic antiviral drugs that have a large number of side effects and have narrow therapeutic window range, while in the other hand herbal formulations have minimized side effects. The advantages of herbal formulation over synthetic drugs encourage us to devise and expand new herbal moieties against the emerging viral infections. The medicinal plants contain phytochemicals that have antiviral properties. In this paper, the activity of antiviral agents from medicinal plants which have importance in Ayurveda, are discussed along with their source.

Molecular docking approach of natural compound from herbal medicine in java against severe acute respiratory syndrome coronavirus-2 receptor

BACKGROUND: Indonesia’s diversity of natural resources presents an intriguing opportunity for the exploration of potential herbal medicines. Numerous compounds, both purified and crude, have been reported to exhibit antiviral activity. The angiotensin-converting enzyme 2 (ACE-2) receptor may be a therapeutic target for severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. We used a search engine to search for herbal medicines with ACE-2 inhibitory activity to predict the potential inhibition of natural compounds (i.e., theaflavin, deoxypodophyllotoxin, gallocatechin, allicin, quercetin, annonamine, Curcumin, 6-gingerol, and cucurbitacin B) to SARS-CoV2–ACE-2 complex. AIM: This research conducted to search potential compound against COVID-19 receptor. METHODS: We performed molecular docking analysis using the ACE-2 receptor protein target from Protein Data Bank. Protein stabilization was carried out to adjust to the body’s physiology, carried out using Pymol by removing water atoms and adding hydrogen atoms. Ligands of active compounds from natural resources were selected and downloaded from the PubChem database, then optimized by Pymol software. RESULTS: The complexes of the tested ligands compounds and ACE-2 receptors, which have a bond strength smaller than the control, were selected for analysis. It was discovered in this study that the aflavin, deoxypodophyllotoxin, gallocatechin, curcumin, and cucurbitacin B had a higher bond affinity than the control ligands XX5. This binding pocket interaction is also the same for all ligands. CONCLUSION: It is hoped that this study would serve as a starting point for future research into possible treatment candidates for SARS-CoV-2.

A review on corona virus and treatment approaches with Allium sativam.

BACKGROUND: Recently reported cases of Covid-19 globally remind us that new diseases are coming while we are unable to provide the treatment for the same. The entire world is facing this viral attack; deaths are increasing day by day as well as infected patients too. Today, in the period of this disease, can we go to the shelter of our traditional medicines? MAIN BODY: In this article, we have taken medicines related to corona and conceptualized their mechanism, which gave us a chance to understand Garlic's mechanism of action, how Garlic can be a weapon in the lane with this disease. This article also tells how we can treat new diseases with our traditional herbs if no modern medicine has been discovered yet. CONCLUSION: The present review is based on the structure of the virus and the targeted site for the drug discovery process with important constituents of Allium sativam. The review work also explains the allicin chemical constituent of Allium sativam which has targeted therapeutic sites related to Covid-19.

The Effect of Allicin on the Proteome of SARS-CoV-2 Infected Calu-3 Cells.

Allicin (diallyl thiosulfinate) is the major thiol-reactive organosulfur compound produced by garlic plants (Allium sativum) upon tissue damage. Allicin exerts its strong antimicrobial activity against bacteria and fungi via S-thioallylation of protein thiols and low molecular weight thiols. Here, we investigated the effect of allicin on SARS-CoV-2 infected Vero E6 and Calu-3 cells. Toxicity tests revealed that Calu-3 cells showed greater allicin tolerance, probably due to >4-fold higher GSH levels compared to the very sensitive Vero E6 cells. Exposure of infected Vero E6 and Calu-3 cells to biocompatible allicin doses led to a ∼60-70% decrease of viral RNA and infectious viral particles. Label-free quantitative proteomics was used to investigate the changes in the Calu-3 proteome after SARS-CoV-2 infection and the effect of allicin on the host-virus proteome. SARS-CoV-2 infection of Calu-3 cells caused a strong induction of the antiviral interferon-stimulated gene (ISG) signature, including several antiviral effectors, such as cGAS, Mx1, IFIT, IFIH, IFI16, IFI44, OAS, and ISG15, pathways of vesicular transport, tight junctions (KIF5A/B/C, OSBPL2, CLTCL1, and ARHGAP17) and ubiquitin modification (UBE2L3/5), as well as reprogramming of host metabolism, transcription and translation. Allicin treatment of infected Calu-3 cells reduced the expression of IFN signaling pathways and ISG effectors and reverted several host pathways to levels of uninfected cells. Allicin further reduced the abundance of the structural viral proteins N, M, S and ORF3 in the host-virus proteome. In conclusion, our data demonstrate the antiviral and immunomodulatory activity of biocompatible doses of allicin in SARS-CoV-2-infected cell cultures. Future drug research should be directed to exploit the thiol-reactivity of allicin derivatives with increased stability and lower human cell toxicity as antiviral lead compounds.

Allium sativum derived carbon dots as a potential theranostic agent to combat the COVID-19 crisis.

Coronavirus disease 2019 (COVID-19) is one of the worst pandemics to have hit the humanity. The manifestations are quite varied, ranging from severe lung infections to being asymptomatic. Hence, there is an urgent need to champion new tools to accelerate the end of this pandemic. Compromised immunity is a primary feature of COVID-19. Allium sativum (AS) is an effective dietary supplement known for its immune-modulatory, antibacterial, anti-inflammatory, anticancer, antifungal, and anti-viral properties. In this paper, it is hypothesized that carbon dots (CDs) derived from AS (AS-CDs) may possess the potential to downregulate the expression of pro-inflammatory cytokines and revert the immunological aberrations to normal in case of COVID-19. CDs have already been explored in the world of nanobiomedicine as a promising theranostic candidates for bioimaging and drug/gene delivery. The antifibrotic and antioxidant effects of AS are elaborated, as demonstrated in several studies. It is found that the most active constituent of AS, allicin has a highly potent antioxidant and reactive oxygen species (ROS) scavenging effect. The antibacterial, antifungal, and anti-viral effects along with their capability of negating inflammatory effects and cytokine storm are discussed. The synthesis of theranostic CDs from AS may provide a novel weapon in the therapeutic armamentarium for the management of COVID-19 infection and, at the same time, could act as a diagnostic agent for COVID-19.

Garlic (Allium sativum L.): a potential unique therapeutic food rich in organosulfur and flavonoid compounds to fight with COVID-19.

Coronavirus disease 2019 (COVID-19) is the current major health crisis in the world. A successful strategy to combat the COVID-19 pandemic is the improvement of nutritional pattern. Garlic is one of the most efficient natural antibiotics against the wide spectrum of viruses and bacteria. Organosulfur (e.g., allicin and alliin) and flavonoid (e.g., quercetin) compounds are responsible for immunomodulatory effects of this healthy spice. The viral replication process is accelerated with the main structural protease of SARS-CoV-2. The formation of hydrogen bonds between this serine-type protease and garlic bioactives in the active site regions inhibits the COVID-19 outbreak. The daily dietary intake of garlic and its derived-products as an adjuvant therapy may improve side effects and toxicity of the main therapeutic drugs with reducing the used dose.