dbAMP 2.0: updated resource for antimicrobial peptides with an enhanced scanning method for genomic and proteomic data

Jhong, Jhih-Hua; Yao, Lantian; Pang, Yuxuan; Li, Zhongyan; Chung, Chia-Ru; Wang, Rulan; Li, Shangfu; Li, Wenshuo; Luo, Mengqi; Ma, Renfei; Huang, Yuqi; Zhu, Xiaoning; Zhang, Jiahong; Feng, Hexiang; Cheng, Qifan; Wang, Chunxuan; Xi, Kun; Wu, Li-Ching; Chang, Tzu-Hao; Horng, Jorng-Tzong; Zhu, Lizhe; Chiang, Ying‐Chih; Wang, Zhuo; Lee, Tzong-Yi

doi:10.1093/nar/gkab1080

Cited by 92 publications

(54 citation statements)

References 64 publications

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“…Research studies showed that DP7, an AMP designed in silico, showed broad-spectrum antimicrobial activity against MDR bacteria, such as P. aeruginosa [102]. Currently, there are many antimicrobial peptides databases (APDs) such as APD3 [63] and collection of antimicrobial peptides (CAMP)R3 [103], as well as online tools for AMP screening and identification such as dbAMP [104] and Ensemble-AMPPred [105].…”

Section: In Silico Designmentioning

confidence: 99%

Antimicrobial Peptides: From Design to Clinical Application

Zhang

Yang

2022

Antibiotics

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Infection of multidrug-resistant (MDR) bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Enterobacteriaceae (CRE), and extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, brings public health issues and causes economic burden. Pathogenic bacteria develop several methods to resist antibiotic killing or inhibition, such as mutation of antibiotic function sites, activation of drug efflux pumps, and enzyme-mediated drug degradation. Antibiotic resistance components can be transferred between bacteria by mobile genetic elements including plasmids, transposons, and integrons, as well as bacteriophages. The development of antibiotic resistance limits the treatment options for bacterial infection, especially for MDR bacteria. Therefore, novel or alternative antibacterial agents are urgently needed. Antimicrobial peptides (AMPs) display multiple killing mechanisms against bacterial infections, including directly bactericidal activity and immunomodulatory function, as potential alternatives to antibiotics. In this review, the development of antibiotic resistance, the killing mechanisms of AMPs, and especially, the design, optimization, and delivery of AMPs are reviewed. Strategies such as structural change, amino acid substitution, conjugation with cell-penetration peptide, terminal acetylation and amidation, and encapsulation with nanoparticles will improve the antimicrobial efficacy, reduce toxicity, and accomplish local delivery of AMPs. In addition, clinical trials in AMP studies or applications of AMPs within the last five years were summarized. Overall, AMPs display diverse mechanisms of action against infection of pathogenic bacteria, and future research studies and clinical investigations will accelerate AMP application.

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Section: In Silico Designmentioning

confidence: 99%

Antimicrobial Peptides: From Design to Clinical Application

Zhang

Yang

2022

Antibiotics

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“…Drug toxicity remains a latent issue [ 20 ], and peptides are no exception to this rule [ 21 ]. Although databases reveal more than 10,000 unique bioactive peptide sequences [ 22 , 23 ], less than 1% of this group became FDA-approved drugs. Several bioactive peptides have shown toxicity, especially their disruptive action on red blood cells (RBCs) [ 24 ].…”

Section: Peptide Drugs Market and Discovery: A Bird’s Eye Viewmentioning

confidence: 99%

Traditional and Computational Screening of Non-Toxic Peptides and Approaches to Improving Selectivity

et al. 2022

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Peptides have positively impacted the pharmaceutical industry as drugs, biomarkers, or diagnostic tools of high therapeutic value. However, only a handful have progressed to the market. Toxicity is one of the main obstacles to translating peptides into clinics. Hemolysis or hemotoxicity, the principal source of toxicity, is a natural or disease-induced event leading to the death of vital red blood cells. Initial screenings for toxicity have been widely evaluated using erythrocytes as the gold standard. More recently, many online databases filled with peptide sequences and their biological meta-data have paved the way toward hemolysis prediction using user-friendly, fast-access machine learning-driven programs. This review details the growing contributions of in silico approaches developed in the last decade for the large-scale prediction of erythrocyte lysis induced by peptides. After an overview of the pharmaceutical landscape of peptide therapeutics, we highlighted the relevance of early hemolysis studies in drug development. We emphasized the computational models and algorithms used to this end in light of historical and recent findings in this promising field. We benchmarked seven predictors using peptides from different data sets, having 7–35 amino acids in length. According to our predictions, the models have scored an accuracy over 50.42% and a minimal Matthew’s correlation coefficient over 0.11. The maximum values for these statistical parameters achieved 100.0% and 1.00, respectively. Finally, strategies for optimizing peptide selectivity were described, as well as prospects for future investigations. The development of in silico predictive approaches to peptide toxicity has just started, but their important contributions clearly demonstrate their potential for peptide science and computer-aided drug design. Methodology refinement and increasing use will motivate the timely and accurate in silico identification of selective, non-toxic peptide therapeutics.

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“…To date, the structures of 26,447 AMPs are known and 3444 of them are molecularly characterized with defined tertiary structure ( Figure 1 ) [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory and Allergenic Properties of Antimicrobial Peptides

Guryanova

Ovchinnikova

2022

IJMS

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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.

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dbAMP 2.0: updated resource for antimicrobial peptides with an enhanced scanning method for genomic and proteomic data

Cited by 92 publications

References 64 publications

Antimicrobial Peptides: From Design to Clinical Application

Antimicrobial Peptides: From Design to Clinical Application

Traditional and Computational Screening of Non-Toxic Peptides and Approaches to Improving Selectivity

Immunomodulatory and Allergenic Properties of Antimicrobial Peptides

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