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1.
Int J Mol Sci ; 24(10)2023 May 20.
Article in English | MEDLINE | ID: covidwho-20239502

ABSTRACT

Antimicrobial peptides (AMPs), or host defence peptides, are short proteins in various life forms. Here we discuss AMPs, which may become a promising substitute or adjuvant in pharmaceutical, biomedical, and cosmeceutical uses. Their pharmacological potential has been investigated intensively, especially as antibacterial and antifungal drugs and as promising antiviral and anticancer agents. AMPs exhibit many properties, and some of these have attracted the attention of the cosmetic industry. AMPs are being developed as novel antibiotics to combat multidrug-resistant pathogens and as potential treatments for various diseases, including cancer, inflammatory disorders, and viral infections. In biomedicine, AMPs are being developed as wound-healing agents because they promote cell growth and tissue repair. The immunomodulatory effects of AMPs could be helpful in the treatment of autoimmune diseases. In the cosmeceutical industry, AMPs are being investigated as potential ingredients in skincare products due to their antioxidant properties (anti-ageing effects) and antibacterial activity, which allows the killing of bacteria that contribute to acne and other skin conditions. The promising benefits of AMPs make them a thrilling area of research, and studies are underway to overcome obstacles and fully harness their therapeutic potential. This review presents the structure, mechanisms of action, possible applications, production methods, and market for AMPs.


Subject(s)
Antimicrobial Peptides , Cosmeceuticals , Cosmeceuticals/pharmacology , Cosmeceuticals/therapeutic use , Antimicrobial Cationic Peptides/pharmacology , Antimicrobial Cationic Peptides/therapeutic use , Antimicrobial Cationic Peptides/chemistry , Anti-Bacterial Agents/pharmacology , Bacteria
2.
Int J Mol Sci ; 24(5)2023 Mar 02.
Article in English | MEDLINE | ID: covidwho-2267175

ABSTRACT

Here we present for the first time a potential wound dressing material implementing aptamers as binding entities to remove pathogenic cells from newly contaminated surfaces of wound matrix-mimicking collagen gels. The model pathogen in this study was the Gram-negative opportunistic bacterium Pseudomonas aeruginosa, which represents a considerable health threat in hospital environments as a cause of severe infections of burn or post-surgery wounds. A two-layered hydrogel composite material was constructed based on an established eight-membered focused anti-P. aeruginosa polyclonal aptamer library, which was chemically crosslinked to the material surface to form a trapping zone for efficient binding of the pathogen. A drug-loaded zone of the composite released the C14R antimicrobial peptide to deliver it directly to the bound pathogenic cells. We demonstrate that this material combining aptamer-mediated affinity and peptide-dependent pathogen eradication can quantitatively remove bacterial cells from the "wound" surface, and we show that the surface-trapped bacteria are completely killed. The drug delivery function of the composite thus represents an extra safeguarding property and thus probably one of the most important additional advances of a next-generation or smart wound dressing ensuring the complete removal and/or eradication of the pathogen of a freshly infected wound.


Subject(s)
Hydrogels , Wound Infection , Humans , Pseudomonas aeruginosa , Antimicrobial Peptides , Wound Infection/microbiology , Bandages , Anti-Bacterial Agents
4.
Microbiol Res ; 265: 127206, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2042033

ABSTRACT

COVID-19 (Coronavirus Disease 2019), a life-threatening viral infection, is caused by a highly pathogenic virus named SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Currently, no treatment is available for COVID-19; hence there is an urgent need to find effective therapeutic drugs to combat COVID-19 pandemic. Considering the fact that the world is facing a major issue of antimicrobial drug resistance, naturally occurring compounds have the potential to achieve this goal. Antimicrobial peptides (AMPs) are naturally occurring antimicrobial agents which are effective against a wide variety of microbial infections. Therefore, the use of AMPs is an attractive therapeutic strategy for the treatment of SARS-CoV-2 infection. This review sheds light on the potential of antimicrobial peptides as antiviral agents followed by a comprehensive description of effective antiviral peptides derived from various natural sources found to be effective against SARS-CoV and other respiratory viruses. It also highlights the mechanisms of action of antiviral peptides with special emphasis on their effectiveness against SARS-CoV-2 infection.


Subject(s)
COVID-19 Drug Treatment , SARS-CoV-2 , Antimicrobial Peptides , Antiviral Agents/pharmacology , Drug Resistance, Multiple , Humans , Pandemics
5.
Colloids Surf B Biointerfaces ; 217: 112693, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-2015062

ABSTRACT

Coronavirus pandemic has evidenced the importance of creating bioactive materials to mitigate viral infections, especially in healthcare settings and public places. Advances in antiviral coatings have led to materials with impressive antiviral performance; however, their application may face health and environmental challenges. Bio-inspired antimicrobial peptides (AMPs) are suitable building blocks for antimicrobial coatings due to their versatile design, scalability, and environmentally friendly features. This review presents the advances and opportunities on the AMPs to create virucidal coatings. The review first describes the fundamental characteristics of peptide structure and synthesis, highlighting the recent findings on AMPs and the role of peptide structure (α-helix, ß-sheet, random, and cyclic peptides) on the virucidal mechanism. The following section presents the advances in AMPs coating on medical devices with a detailed description of the materials coated and the targeted pathogens. The use of peptides in vaccine formulations is also reported, emphasizing the molecular interaction of peptides with different viruses and the current clinical stage of each formulation. The role of several materials (metallic particles, inorganic materials, and synthetic polymers) in the design of antiviral coatings is also presented, discussing the advantages and the drawbacks of each material. The final section offers future directions and opportunities for using AMPs on antiviral coatings to prevent viral outbreaks.


Subject(s)
Anti-Infective Agents , Viruses , Anti-Bacterial Agents , Anti-Infective Agents/pharmacology , Antimicrobial Cationic Peptides/chemistry , Antimicrobial Cationic Peptides/pharmacology , Antimicrobial Peptides , Antiviral Agents/pharmacology
6.
Front Immunol ; 13: 880961, 2022.
Article in English | MEDLINE | ID: covidwho-1933665

ABSTRACT

COVID-19 is characterized by hyperactivation by inflammatory cytokines and recruitment of macrophages, neutrophils, and other immune cells, all hallmarks of a strong inflammatory response that can lead to severe complications and multi-organ damage. Mortality in COVID-19 patients is associated with a high prevalence of neutrophil extracellular trap (NET) formation and microthrombosis that are exacerbated by hyperglycemia, diabetes, and old age. SARS-CoV-2 infection in humans and non-human primates have revealed long-term neurological consequences of COVID-19, possibly concomitant with the formation of Lewy bodies in the brain and invasion of the nervous system via the olfactory bulb. In this paper, we review the relevance of the human cathelicidin LL-37 in SARS-CoV-2 infections. LL-37 is an immunomodulatory, host defense peptide with direct anti-SARS-CoV-2 activity, and pleiotropic effects on the inflammatory response, neovascularization, Lewy body formation, and pancreatic islet cell function. The bioactive form of vitamin D and a number of other compounds induce LL-37 expression and one might predict its upregulation, could reduce the prevalence of severe COVID-19. We hypothesize upregulation of LL-37 will act therapeutically, facilitating efficient NET clearance by macrophages, speeding endothelial repair after inflammatory tissue damage, preventing α-synuclein aggregation, and supporting blood-glucose level stabilization by facilitating insulin release and islet ß-cell neogenesis. In addition, it has been postulated that LL-37 can directly bind the S1 domain of SARS-CoV-2, mask angiotensin converting enzyme 2 (ACE2) receptors, and limit SARS-CoV-2 infection. Purposeful upregulation of LL-37 could also serve as a preventative and therapeutic strategy for SARS-CoV-2 infections.


Subject(s)
COVID-19 , Animals , Antimicrobial Cationic Peptides , Antimicrobial Peptides , Humans , Peptidyl-Dipeptidase A/metabolism , SARS-CoV-2 , Cathelicidins
7.
Front Immunol ; 13: 851642, 2022.
Article in English | MEDLINE | ID: covidwho-1933645

ABSTRACT

The rapid evolution of highly infectious pathogens is a major threat to global public health. In the front line of defense against bacteria, fungi, and viruses, antimicrobial peptides (AMPs) are naturally produced by all living organisms and offer new possibilities for next-generation antibiotic development. However, the low yields and difficulties in the extraction and purification of AMPs have hindered their industry and scientific research applications. To overcome these barriers, we enabled high expression of bomidin, a commercial recombinant AMP based upon bovine myeloid antimicrobial peptide-27. This novel AMP, which can be expressed in Escherichia coli by adding methionine to the bomidin sequence, can be produced in bulk and is more biologically active than chemically synthesized AMPs. We verified the function of bomidin against a variety of bacteria and enveloped viruses, including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), herpes simplex virus (HSV), dengue virus (DENV), and chikungunya virus (CHIKV). Furthermore, based on the molecular modeling of bomidin and membrane lipids, we elucidated the possible mechanism by which bomidin disrupts bacterial and viral membranes. Thus, we obtained a novel AMP with an optimized, efficient heterologous expression system for potential therapeutic application against a wide range of life-threatening pathogens.


Subject(s)
COVID-19 , Viruses , Adenosine Monophosphate , Animals , Antimicrobial Peptides , Antiviral Agents/pharmacology , Cattle , SARS-CoV-2
8.
Front Immunol ; 13: 921483, 2022.
Article in English | MEDLINE | ID: covidwho-1903033

ABSTRACT

Although COVID-19 has captured most of the public health attention, antimicrobial resistance (AMR) has not disappeared. To prevent the escape of resistant microorganisms in animals or environmental reservoirs a "one health approach" is desirable. In this context of COVID-19, AMR has probably been affected by the inappropriate or over-use of antibiotics. The increased use of antimicrobials and biocides for disinfection may have enhanced the prevalence of AMR. Antibiotics have been used empirically in patients with COVID-19 to avoid or prevent bacterial coinfection or superinfections. On the other hand, the measures to prevent the transmission of COVID-19 could have reduced the risk of the emergence of multidrug-resistant microorganisms. Since we do not currently have a sterilizing vaccine against SARS-CoV-2, the virus may still multiply in the organism and new mutations may occur. As a consequence, there is a risk of the appearance of new variants. Nature-derived anti-infective agents, such as antibodies and antimicrobial peptides (AMPs), are very promising in the fight against infectious diseases, because they are less likely to develop resistance, even though further investigation is still required.


Subject(s)
Anti-Infective Agents , COVID-19 Drug Treatment , Animals , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/pharmacology , Anti-Infective Agents/therapeutic use , Antimicrobial Peptides , COVID-19 Vaccines , Drug Resistance, Bacterial , Humans , SARS-CoV-2
9.
Mol Biol Rep ; 49(10): 10039-10050, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1859057

ABSTRACT

BACKGROUND: Antimicrobial peptides (AMPs) are a diverse class of molecules that represent a vital part of innate immunity. AMPs are evolutionarily conserved molecules that exhibit structural and functional diversity. They provide a possible solution to the antibiotic-resistance crisis. MAIN TEXT: These small cationic peptides can target bacteria, fungi, and viruses, as well as cancer cells. Their unique action mechanisms, rare antibiotic-resistant variants, broad-spectrum activity, low toxicity, and high specificity encourage pharmaceutical industries to conduct clinical trials to develop them as therapeutic drugs. The rapid development of computer-assisted strategies accelerated the identification of AMPs. The Antimicrobial Peptide Database (APD) so far contains 3324 AMPs from different sources. In addition to their applications in different fields, some AMPs demonstrated the potential to combat COVID-19, and hinder viral infectivity in diverse ways. CONCLUSIONS: This review provides a brief history of AMPs and their features, including classification, evolution, sources and mechanisms of action, biosynthesis pathway, and identification techniques. Furthermore, their different applications, challenges to clinical applications, and their potential use against COVID-19 are presented.


Subject(s)
Antimicrobial Cationic Peptides , COVID-19 Drug Treatment , Anti-Bacterial Agents/pharmacology , Antimicrobial Cationic Peptides/pharmacology , Antimicrobial Cationic Peptides/therapeutic use , Antimicrobial Peptides , Bacteria , Humans
10.
Molecules ; 27(9)2022 Apr 21.
Article in English | MEDLINE | ID: covidwho-1841404

ABSTRACT

Antimicrobial peptides are a type of small-molecule peptide that widely exist in nature and are components of the innate immunity of almost all living things. They play an important role in resisting foreign invading microorganisms. Antimicrobial peptides have a wide range of antibacterial activities against bacteria, fungi, viruses and other microorganisms. They are active against traditional antibiotic-resistant strains and do not easily induce the development of drug resistance. Therefore, they have become a hot spot of medical research and are expected to become a new substitute for fighting microbial infection and represent a new method for treating drug-resistant bacteria. This review briefly introduces the source and structural characteristics of antimicrobial peptides and describes those that have been used against common clinical microorganisms (bacteria, fungi, viruses, and especially coronaviruses), focusing on their antimicrobial mechanism of action and clinical application prospects.


Subject(s)
Anti-Infective Agents , Viruses , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/pharmacology , Antimicrobial Cationic Peptides/chemistry , Antimicrobial Cationic Peptides/pharmacology , Antimicrobial Peptides , Bacteria , Fungi
11.
Int J Mol Sci ; 23(5)2022 Feb 24.
Article in English | MEDLINE | ID: covidwho-1736942

ABSTRACT

With the growing problem of the emergence of antibiotic-resistant bacteria, the search for alternative ways to combat bacterial infections is extremely urgent. While analyzing the effect of antimicrobial peptides (AMPs) on immunocompetent cells, their effect on all parts of the immune system, and on humoral and cellular immunity, is revealed. AMPs have direct effects on neutrophils, monocytes, dendritic cells, T-lymphocytes, and mast cells, participating in innate immunity. They act on B-lymphocytes indirectly, enhancing the induction of antigen-specific immunity, which ultimately leads to the activation of adaptive immunity. The adjuvant activity of AMPs in relation to bacterial and viral antigens was the reason for their inclusion in vaccines and made it possible to formulate the concept of a "defensin vaccine" as an innovative basis for constructing vaccines. The immunomodulatory function of AMPs involves their influence on cells in the nearest microenvironment, recruitment and activation of other cells, supporting the response to pathogenic microorganisms and completing the inflammatory process, thus exhibiting a systemic effect. For the successful use of AMPs in medical practice, it is necessary to study their immunomodulatory activity in detail, taking into account their pleiotropy. The degree of maturity of the immune system and microenvironment can contribute to the prevention of complications and increase the effectiveness of therapy, since AMPs can suppress inflammation in some circumstances, but aggravate the response and damage of organism in others. It should also be taken into account that the real functions of one or another AMP depend on the types of total regulatory effects on the target cell, and not only on properties of an individual peptide. A wide spectrum of biological activity, including direct effects on pathogens, inactivation of bacterial toxins and influence on immunocompetent cells, has attracted the attention of researchers, however, the cytostatic activity of AMPs against normal cells, as well as their allergenic properties and low stability to host proteases, are serious limitations for the medical use of AMPs. In this connection, the tasks of searching for compounds that selectively affect the target and development of an appropriate method of application become critically important. The scope of this review is to summarize the current concepts and newest advances in research of the immunomodulatory activity of natural and synthetic AMPs, and to examine the prospects and limitations of their medical use.


Subject(s)
Antimicrobial Cationic Peptides , Antimicrobial Peptides , Allergens/pharmacology , Antimicrobial Cationic Peptides/chemistry , Bacteria , Immunity, Innate , Immunomodulation
12.
Expert Opin Drug Discov ; 17(5): 473-487, 2022 05.
Article in English | MEDLINE | ID: covidwho-1730521

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19), which emerged as a major public health threat, has affected >400 million people globally leading to >5 million mortalities to date. Treatments of COVID-19 are still to be developed as the available therapeutic approaches are not able to combat the virus causing the disease (severe acute respiratory syndrome coronavirus-2; SARS-CoV-2) satisfactorily. However, antiviral peptides (AVPs) have demonstrated prophylactic and therapeutic effects against many coronaviruses (CoVs). AREAS COVERED: This review critically discusses various types of AVPs evaluated for the treatment of COVID-19 along with their mechanisms of action. Furthermore, the peptides inhibiting the entry of the virus by targeting its binding to angiotensin-converting enzyme 2 (ACE2) or integrins, fusion mechanism as well as activation of proteolytic enzymes (cathepsin L, transmembrane serine protease 2 (TMPRSS2), or furin) are also discussed. EXPERT OPINION: Although extensively investigated, successful treatment of COVID-19 is still a challenge due to emergence of virus mutants. Antiviral peptides are anticipated to be blockbuster drugs for the management of this serious infection because of their formulation and therapeutic advantages. Although they may act on different pathways, AVPs having a multi-targeted approach are considered to have the upper hand in the management of this infection.


Subject(s)
COVID-19 Drug Treatment , Antimicrobial Peptides , Antiviral Agents/pharmacology , Humans , SARS-CoV-2 , Virus Internalization
13.
Brief Bioinform ; 23(2)2022 03 10.
Article in English | MEDLINE | ID: covidwho-1684526

ABSTRACT

The application of machine intelligence in biological sciences has led to the development of several automated tools, thus enabling rapid drug discovery. Adding to this development is the ongoing COVID-19 pandemic, due to which researchers working in the field of artificial intelligence have acquired an active interest in finding machine learning-guided solutions for diseases like mucormycosis, which has emerged as an important post-COVID-19 fungal complication, especially in immunocompromised patients. On these lines, we have proposed a temporal convolutional network-based binary classification approach to discover new antifungal molecules in the proteome of plants and animals to accelerate the development of antifungal medications. Although these biomolecules, known as antifungal peptides (AFPs), are part of an organism's intrinsic host defense mechanism, their identification and discovery by traditional biochemical procedures is arduous. Also, the absence of a large dataset on AFPs is also a considerable impediment in building a robust automated classifier. To this end, we have employed the transfer learning technique to pre-train our model on antibacterial peptides. Subsequently, we have built a classifier that predicts AFPs with accuracy and precision of 94%. Our classifier outperforms several state-of-the-art models by a considerable margin. The results of its performance were proven as statistically significant using the Kruskal-Wallis H test, followed by a post hoc analysis performed using the Tukey honestly significant difference (HSD) test. Furthermore, we identified potent AFPs in representative animal (Histatin) and plant (Snakin) proteins using our model. We also built and deployed a web app that is freely available at https://tcn-afppred.anvil.app/ for the identification of AFPs in protein sequences.


Subject(s)
Antifungal Agents/chemistry , Antimicrobial Peptides/chemistry , Deep Learning , Drug Discovery/methods , Neural Networks, Computer , Algorithms , Antifungal Agents/pharmacology , Antimicrobial Peptides/pharmacology , Artificial Intelligence , Databases, Factual , Humans , ROC Curve , Reproducibility of Results , Software , Workflow
14.
Comput Math Methods Med ; 2022: 9735626, 2022.
Article in English | MEDLINE | ID: covidwho-1677416

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was characterized as a pandemic by the World Health Organization (WHO) in Dec. 2019. SARS-CoV-2 binds to the cell membrane through spike proteins on its surface and infects the cell. Furin, a host-cell enzyme, possesses a binding site for the spike protein. Thus, molecules that block furin could potentially be a therapeutic solution. Defensins are antimicrobial peptides that can hypothetically inhibit furin because of their arginine-rich structure. Theta-defensins, a subclass of defensins, have attracted attention as drug candidates due to their small size, unique structure, and involvement in several defense mechanisms. Theta-defensins could be a potential treatment for COVID-19 through furin inhibition and an anti-inflammatory mechanism. Note that inflammatory events are a significant and deadly condition that could happen at the later stages of COVID-19 infection. Here, the potential of theta-defensins against SARS-CoV-2 infection was investigated through in silico approaches. Based on docking analysis results, theta-defensins can function as furin inhibitors. Additionally, a novel candidate peptide against COVID-19 with optimal properties regarding antigenicity, stability, electrostatic potential, and binding strength was proposed. Further in vitro/in vivo investigations could verify the efficiency of the designed novel peptide.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/metabolism , Defensins/pharmacology , Drug Design , Furin/antagonists & inhibitors , Animals , Antimicrobial Peptides/chemistry , Catalytic Domain , Cell Membrane/virology , Computer Simulation , Data Mining , Furin/chemistry , Humans , Inflammation , Models, Molecular , Molecular Docking Simulation , Peptides/chemistry , Software , Spike Glycoprotein, Coronavirus , Static Electricity , COVID-19 Drug Treatment
15.
Int J Mol Sci ; 23(2)2022 Jan 14.
Article in English | MEDLINE | ID: covidwho-1625084

ABSTRACT

Viral infections represent a serious threat to the world population and are becoming more frequent. The search and identification of broad-spectrum antiviral molecules is necessary to ensure new therapeutic options, since there is a limited availability of effective antiviral drugs able to eradicate viral infections, and consequently due to the increase of strains that are resistant to the most used drugs. Recently, several studies on antimicrobial peptides identified them as promising antiviral agents. In detail, amphibian skin secretions serve as a rich source of natural antimicrobial peptides. Their antibacterial and antifungal activities have been widely reported, but their exploitation as potential antiviral agents have yet to be fully investigated. In the present study, the antiviral activity of the peptide derived from the secretion of Rana tagoi, named AR-23, was evaluated against both DNA and RNA viruses, with or without envelope. Different assays were performed to identify in which step of the infectious cycle the peptide could act. AR-23 exhibited a greater inhibitory activity in the early stages of infection against both DNA (HSV-1) and RNA (MeV, HPIV-2, HCoV-229E, and SARS-CoV-2) enveloped viruses and, on the contrary, it was inactive against naked viruses (PV-1). Altogether, the results indicated AR-23 as a peptide with potential therapeutic effects against a wide variety of human viruses.


Subject(s)
Amphibian Proteins/pharmacology , Antimicrobial Peptides/pharmacology , Antiviral Agents/pharmacology , Ranidae/metabolism , Animals , Antimicrobial Cationic Peptides/pharmacology , Cell Survival/drug effects , Chlorocebus aethiops , DNA Viruses/drug effects , RNA Viruses/drug effects , SARS-CoV-2/drug effects , Vero Cells , Viral Envelope/drug effects , Viral Plaque Assay , Virus Diseases/drug therapy
16.
Rev Soc Bras Med Trop ; 54: e04612021, 2021.
Article in English | MEDLINE | ID: covidwho-1598762

ABSTRACT

Before eliciting an adaptive immune response, SARS-CoV-2 must overcome seven constitutive respiratory defense barriers. The first is the mucus covering the respiratory tract's luminal surface, which entraps inhaled particles, including infectious agents, and eliminates them by mucociliary clearance. The second barrier comprises various components present in the airway lining fluid, the surfactants. Besides providing low surface tension that allows efficient gas exchange at the alveoli, surfactants inhibit the invasion of epithelial cells by respiratory viruses, enhance pathogen uptake by phagocytes, and regulate immune cells' functions. The respiratory tract microbiota constitutes the third defense barrier against SARS-CoV-2. It activates the innate and adaptive immune cells and elicits anti-infectious molecules such as secretory IgA antibodies, defensins, and interferons. The fourth defense barrier comprises the antimicrobial peptides defensins, and lactoferrin. They show direct antiviral activity, inhibit viral fusion, and modulate the innate and adaptive immune responses. Secretory IgA antibodies, the fifth defense barrier, besides protecting the local microbiota against noxious agents, also inhibit SARS-CoV-2 cell invasion. If the virus overcomes this barrier, it reaches its target, the respiratory epithelial cells. However, these cells also act as a defense barrier, the sixth one, since they hinder the virus' access to receptors and produce antiviral and immunomodulatory molecules such as interferons, lactoferrin, and defensins. Finally, the sensing of the virus by the cells of innate immunity, the last constitutive defense barrier, elicits a cascade of signals that activate adaptive immune cells and may inhibit the development of productive infection. The subject of the present essay is discussing these mechanisms.


Subject(s)
COVID-19 , Immunity, Innate , Antibodies, Viral/immunology , Antimicrobial Peptides/immunology , COVID-19/immunology , Humans , Immunoglobulin A/immunology , Interferons/immunology , Lung/immunology , Lung/virology , SARS-CoV-2
17.
Nucleic Acids Res ; 50(D1): D460-D470, 2022 01 07.
Article in English | MEDLINE | ID: covidwho-1546004

ABSTRACT

The last 18 months, or more, have seen a profound shift in our global experience, with many of us navigating a once-in-100-year pandemic. To date, COVID-19 remains a life-threatening pandemic with little to no targeted therapeutic recourse. The discovery of novel antiviral agents, such as vaccines and drugs, can provide therapeutic solutions to save human beings from severe infections; however, there is no specifically effective antiviral treatment confirmed for now. Thus, great attention has been paid to the use of natural or artificial antimicrobial peptides (AMPs) as these compounds are widely regarded as promising solutions for the treatment of harmful microorganisms. Given the biological significance of AMPs, it was obvious that there was a significant need for a single platform for identifying and engaging with AMP data. This led to the creation of the dbAMP platform that provides comprehensive information about AMPs and facilitates their investigation and analysis. To date, the dbAMP has accumulated 26 447 AMPs and 2262 antimicrobial proteins from 3044 organisms using both database integration and manual curation of >4579 articles. In addition, dbAMP facilitates the evaluation of AMP structures using I-TASSER for automated protein structure prediction and structure-based functional annotation, providing predictive structure information for clinical drug development. Next-generation sequencing (NGS) and third-generation sequencing have been applied to generate large-scale sequencing reads from various environments, enabling greatly improved analysis of genome structure. In this update, we launch an efficient online tool that can effectively identify AMPs from genome/metagenome and proteome data of all species in a short period. In conclusion, these improvements promote the dbAMP as one of the most abundant and comprehensively annotated resources for AMPs. The updated dbAMP is now freely accessible at http://awi.cuhk.edu.cn/dbAMP.


Subject(s)
Antimicrobial Peptides , Databases, Factual , Software , Antimicrobial Peptides/chemistry , Antimicrobial Peptides/pharmacology , Genomics , Open Reading Frames , Protein Conformation , Proteomics
18.
Cells ; 10(12)2021 11 25.
Article in English | MEDLINE | ID: covidwho-1542428

ABSTRACT

Acute respiratory distress syndrome (ARDS) is a serious lung condition characterized by severe hypoxemia leading to limitations of oxygen needed for lung function. In this study, we investigated the effect of anandamide (AEA), an endogenous cannabinoid, on Staphylococcal enterotoxin B (SEB)-mediated ARDS in female mice. Single-cell RNA sequencing data showed that the lung epithelial cells from AEA-treated mice showed increased levels of antimicrobial peptides (AMPs) and tight junction proteins. MiSeq sequencing data on 16S RNA and LEfSe analysis demonstrated that SEB caused significant alterations in the microbiota, with increases in pathogenic bacteria in both the lungs and the gut, while treatment with AEA reversed this effect and induced beneficial bacteria. AEA treatment suppressed inflammation both in the lungs as well as gut-associated mesenteric lymph nodes (MLNs). AEA triggered several bacterial species that produced increased levels of short-chain fatty acids (SCFAs), including butyrate. Furthermore, administration of butyrate alone could attenuate SEB-mediated ARDS. Taken together, our data indicate that AEA treatment attenuates SEB-mediated ARDS by suppressing inflammation and preventing dysbiosis, both in the lungs and the gut, through the induction of AMPs, tight junction proteins, and SCFAs that stabilize the gut-lung microbial axis driving immune homeostasis.


Subject(s)
Arachidonic Acids/therapeutic use , Endocannabinoids/therapeutic use , Gastrointestinal Microbiome , Gastrointestinal Tract/pathology , Lung/pathology , Polyunsaturated Alkamides/therapeutic use , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/microbiology , Animals , Antimicrobial Peptides/metabolism , Arachidonic Acids/pharmacology , Butyrates/metabolism , Cecum/pathology , Cell Separation , Colon/drug effects , Colon/pathology , Discriminant Analysis , Dysbiosis/complications , Dysbiosis/microbiology , Endocannabinoids/pharmacology , Enterotoxins , Female , Gastrointestinal Tract/drug effects , Lymph Nodes/drug effects , Lymph Nodes/pathology , Lymphocyte Activation/drug effects , Mice, Inbred C57BL , Pneumonia/drug therapy , Pneumonia/microbiology , Polyunsaturated Alkamides/pharmacology , Respiratory Distress Syndrome/complications , T-Lymphocytes/drug effects
19.
Med Res Rev ; 42(3): 1023-1036, 2022 05.
Article in English | MEDLINE | ID: covidwho-1525477

ABSTRACT

Several natural antimicrobial peptides (AMPs), including the novel semisynthetic lipoglycopeptide antibiotics telavancin, dalbavancin, and oritavancin, have been approved for clinical use to address the growing problem of multiple antibiotic-resistant Gram-positive bacterial infections. Nevertheless, the efficacy of these antibiotics has already been compromised. The SARS-CoV-2 pandemic led to the increased clinical use of all antibiotics, further promoting the development of bacterial resistance. Therefore, it is critical to gain a deeper understanding of the role of resistance mechanisms to minimize the consequential risks of long-term antibiotic use and misuse. Here, we summarize for the first time the current knowledge of resistance mechanisms that have been shown to cause resistance to clinically used AMPs, with particular focus on membrane proteins that have been reported to interfere with the activity of AMPs by affecting the binding of AMPs to bacteria.


Subject(s)
COVID-19 , Gram-Positive Bacterial Infections , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Antimicrobial Peptides , Gram-Positive Bacterial Infections/drug therapy , Gram-Positive Bacterial Infections/metabolism , Gram-Positive Bacterial Infections/microbiology , Humans , Membrane Proteins , SARS-CoV-2
20.
Int J Mol Sci ; 22(21)2021 Oct 21.
Article in English | MEDLINE | ID: covidwho-1512372

ABSTRACT

Botany-derived antimicrobial peptides (BAMPs), a class of small, cysteine-rich peptides produced in plants, are an important component of the plant immune system. Both in vivo and in vitro experiments have demonstrated their powerful antimicrobial activity. Besides in plants, BAMPs have cross-kingdom applications in human health, with toxic and/or inhibitory effects against a variety of tumor cells and viruses. With their diverse molecular structures, broad-spectrum antimicrobial activity, multiple mechanisms of action, and low cytotoxicity, BAMPs provide ideal backbones for drug design, and are potential candidates for plant protection and disease treatment. Lots of original research has elucidated the properties and antimicrobial mechanisms of BAMPs, and characterized their surface receptors and in vivo targets in pathogens. In this paper, we review and introduce five kinds of representative BAMPs belonging to the pathogenesis-related protein family, dissect their antifungal, antiviral, and anticancer mechanisms, and forecast their prospects in agriculture and global human health. Through the deeper understanding of BAMPs, we provide novel insights for their applications in broad-spectrum and durable plant disease prevention and control, and an outlook on the use of BAMPs in anticancer and antiviral drug design.


Subject(s)
Antimicrobial Peptides/genetics , Antimicrobial Peptides/metabolism , Antimicrobial Peptides/pharmacology , Agriculture , Anti-Infective Agents/pharmacology , Antimicrobial Cationic Peptides/pharmacology , Antiviral Agents/pharmacology , Drug Design/methods , Humans , Plant Immunity/drug effects , Plants/drug effects , Viruses/drug effects
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