production-and-testing-of-antimicrobial-peptides-and-their-mimics

Production and Testing of Antimicrobial Peptides and Their Mimics

Antimicrobial peptides (AMPs) and their synthetic mimics are emerging as promising alternatives to conventional antibiotics, particularly in response to ...

University of New South Wales

Most of the typical chemokine receptors (CKRs) have been identified as coreceptors for a variety of human and simian immunodeficiency viruses (HIVs and SIVs). This study evaluated CCRL2 to examine if it was an HIV/SIV coreceptor.

C-C Chemokine receptor-like 2 (CCRL2) acts as coreceptor for human immunodeficiency virus-2.

Ocular signs and symptoms of monkeypox virus infection, and possible role of the eye in transmission of the virus.

Viral epidemics are occurring frequently, and the COVID-19 viral pandemic has resulted in at least 6.5 million deaths worldwide. Although antiviral therapeutics are available, these may not have sufficient effect. The emergence of resistant or novel viruses requires new therapies. Cationic antimicrobial peptides are agents of the innate immune system that may offer a promising solution to viral infections. These peptides are gaining attention as possible therapies for viral infections or for use as prophylactic agents to prevent viral spread. This narrative review examines antiviral peptides, their structural features, and mechanism of activity. A total of 156 cationic antiviral peptides were examined for information of their mechanism of action against both enveloped and non-enveloped viruses. Antiviral peptides can be isolated from various natural sources or can be generated synthetically. The latter tend to be more specific and effective and can be made to have a broad spectrum of activity with minimal side effects. Their unique properties of being positively charged and amphipathic enable their main mode of action which is to target and disrupt viral lipid envelopes, thereby inhibiting viral entry and replication. This review offers a comprehensive summary of the current understanding of antiviral peptides, which could potentially aid in the design and creation of novel antiviral medications.

A review of the antiviral activity of cationic antimicrobial peptides.

The development of potent antiviral agents is of utmost importance to combat the global burden of viral infections. Traditional antiviral drug development involves targeting specific viral proteins, which may lead to the emergence of resistant strains. To explore alternative strategies, we investigated the antiviral potential of antimicrobial peptidomimetic compounds. In this study, we evaluated the antiviral potential of 17 short anthranilamide-based peptidomimetic compounds against two viruses: Murine hepatitis virus 1 (MHV-1) which is a surrogate of human coronaviruses and herpes simplex virus 1 (HSV-1). The half-maximal inhibitory concentration (IC) values of these compounds were determined in vitro to assess their potency as antiviral agents. Compounds  and  displayed the most potent inhibitory effects with IC values of 2.38 μM, and 6.3 μM against MHV-1 while compounds  and  showed IC values of 14.8 μM and 13 μM against HSV-1. Multiple antiviral assessments and microscopic images obtained through transmission electron microscopy (TEM) collectively demonstrated that these compounds exert a direct influence on the viral envelope. Based on this outcome, it can be concluded that peptidomimetic compounds could offer a new approach for the development of potent antiviral agents.

Antiviral Activity of Anthranilamide Peptidomimetics against Herpes Simplex Virus 1 and a Coronavirus.

The ongoing battle against viral pandemics continues, with the possibility of future outbreaks. The search for effective antiviral compounds that can combat a diverse range of viruses continues to be a focal point of research. This study investigated the efficacy of two natural antimicrobial peptides (AMPs) (lactoferricin and LL-37), two synthetic AMPs (melimine and Mel4), and nine AMP mimics (758, 1091, 1096, 1083, 610, NAPL, 3-BIPL, 4-BIPL, and Sau-22) against influenza A virus strains H1N1 and H3N2, human adenovirus 5 (HAdV-5), and murine norovirus 1 (MNV-1). These compounds were tested using virus pre-treatment, cell pre-treatment, or post-cell entry treatment assays, electron microscopy, and circular dichroism (CD), alongside evaluations of cytotoxicity against the host cells. After virus pre-treatment, the AMP mimics 610 and Sau-22 had relatively low IC values for influenza strains H1N1 (2.35 and 6.93 µM, respectively) and H3N2 (3.7 and 5.34 µM, respectively). Conversely, natural and synthetic AMPs were not active against these strains. For the non-enveloped viruses, the AMP Mel4 and mimic 1083 had moderate activity against HAdV-5 (Mel4 IC = 47.4 µM; 1083 IC = 47.2 µM), whereas all AMPs, but none of the mimics, were active against norovirus (LL-37 IC = 4.2 µM; lactoferricin IC = 23.18 µM; melimine IC = 4.8 µM; Mel4 IC = 8.6 µM). Transmission electron microscopy demonstrated that the mimics targeted the outer envelope of influenza viruses, while the AMPs targeted the capsid of non-enveloped viruses. CD showed that Mel4 adopted an α-helical structure in a membrane mimetic environment, but mimic 758 remained unstructured. The diverse activity against different virus groups is probably influenced by charge, hydrophobicity, size, and, in the case of natural and synthetic AMPs, their secondary structure. These findings underscore the potential of peptides and mimics as promising candidates for antiviral therapeutics against both enveloped and non-enveloped viruses.

Exploring the Efficacy of Peptides and Mimics against Influenza A Virus, Adenovirus, and Murine Norovirus.

Antimicrobial resistance is a critical global challenge in the 21st century, validating Sir Alexander Fleming's warning about the misuse of antibiotics leading to resistant microbes. With a dwindling arsenal of effective antibiotics, it is imperative to concentrate on alternative antimicrobial strategies. Previous studies have not comprehensively discussed the advantages and limitations of various strategies, including bacteriophage therapy, probiotics, immunotherapies, photodynamic therapy, essential oils, nanoparticles and antimicrobial peptides (AMPs) within a single review. This review addresses that gap by providing an overview of these various non-antibiotic antimicrobial strategies, highlighting their pros and cons, with a particular emphasis on antimicrobial peptides (AMPs). We explore the mechanism of action of AMPs against bacteria, viruses, fungi and parasites. While these peptides hold significant promise, their application in mainstream drug development is hindered by challenges such as low bioavailability and potential toxicity. However, advancements in peptide engineering and chemical modifications offer solutions to enhance their clinical utility. Additionally, this review presents updates on strategies aimed at improving the cost, stability and selective toxicity of AMPs through the development of peptidomimetics. These molecules have demonstrated effective activity against a broad range of pathogens, making them valuable candidates for integration into surface coatings to prevent device-associated infections. Furthermore, we discuss various approaches for attaching and functionalising these peptides on surfaces. Finally, we recommend comprehensive in vivo studies to evaluate the efficacy of AMPs and their mimetics, investigate their synergistic combinations with other molecules and assess their potential as coatings for medical devices.

Harnessing Non-Antibiotic Strategies to Counter Multidrug-Resistant Clinical Pathogens with Special Reference to Antimicrobial Peptides and Their Coatings.

The global health impact of viruses highlights the urgent need for innovative antiviral strategies. This study investigated the synergistic potential of two anthranilamide-based peptide mimics (RK610 and RK758) in combination, and one peptide mimic (RK610) in combination with the cationic peptides Mel4 and melimine, against murine hepatitis virus (a coronavirus; MHV-1), influenza virus (H1N1), and Herpes simplex virus (HSV-1). Checkerboard assays demonstrated RK610+RK758 had synergy against MHV-1 and H1N1 (∑FICI values of 0.14 and 0.5, respectively), while RK610+Mel4 showed potent synergy against HSV-1 (∑FICI = 0.18). Co-treatment outperformed sequential application. Transmission electron microscopy confirmed structural damage to virions, while cytotoxicity assays indicated that all tested combinations were non-toxic in MDCK, A9, and Vero cells, except for melimine and RK610+melimine with A9 cells. Biophysical analyses using DOPC (100 %) and DOPC: POPS (70:30) lipids provided mechanistic ideas into peptide-mimic interactions with lipid envelopes. Tethered bilayer lipid membranes (tBLMs) in conjunction with electrical impedance spectroscopy revealed that both peptide mimics and their combinations reduced membrane conductance, regardless of lipid composition. Quartz crystal microbalance with dissipation monitoring (QCM-D) revealed that RK610 and RK758 induced mass addition at the outer layer, significantly increasing with POPS. In DOPC, RK610 increased the surface pressure in a Langmuir-Blodgett trough while RK758 reduced it. The 610 + 758 and 610+Mel4 combinations raised maximum pressures. In DOPC + POPS, RK758 destabilized the monolayer (35 mN/m, no plateau), whereas combinations restored stability. These findings highlight peptide mimics as broad-spectrum antiviral agents that show synergy to target viral envelopes, paving the way for safer and low-resistance therapeutics.

Synergistic effects of peptide mimics against enveloped viruses.

Microbial keratitis is a major cause of monocular blindness worldwide. Trauma and contact lens wear are major risk factors. Bacteria are a major cause, but fungi, viruses, and  can also cause the disease. Therapeutic options are dwindling with the rise of antimicrobial resistance in all of these microbes, but especially bacteria. Infection with resistant strains results in worse clinical outcomes. New antimicrobial therapies are being developed but most have yet to be either used to treat ocular infections or become commercially available. For bacterial keratitis, antimicrobial peptides (AMPs) are a potential new option, as are bacteriophages and even bacteria that eat other bacteria or maggot secretions. For fungal keratitis, ocular natamycin, with oral ketoconazole or voriconazole treatments, offer improved outcomes for severe cases. For viral keratitis, AMPs again offer hope as new therapeutics, as do RNA interference and CRISPR-Cas systems. The recent release of a commercially available polyhexamethylene biguanide eye drop is a step forward, but new therapies that can kill both  trophozoites and cysts are still needed. Beyond antibiotics, photoactivated chromophores for keratitis-corneal collagen cross-linking and photodynamic therapy have been successfully used. Therapies for large ulcers or scarring include corneal gluing, tissue scaffolds such as amniotic membrane or conjunctival flaps, and tissue replacement through penetrating or lamellar keratoplasty.

Article	Year
C-C Chemokine receptor-like 2 (CCRL2) acts as coreceptor for human immunodeficiency virus-2. Briefings in bioinformatics\| PubMed ID: 33253374	2021
Ocular signs and symptoms of monkeypox virus infection, and possible role of the eye in transmission of the virus. Contact lens & anterior eye : the journal of the British Contact Lens Association\| PubMed ID: 36585302	2023
A review of the antiviral activity of cationic antimicrobial peptides. Peptides\| PubMed ID: 37172781	2023
Antiviral Activity of Anthranilamide Peptidomimetics against Herpes Simplex Virus 1 and a Coronavirus. Antibiotics (Basel, Switzerland)\| PubMed ID: 37760732	2023
Exploring the Efficacy of Peptides and Mimics against Influenza A Virus, Adenovirus, and Murine Norovirus. International journal of molecular sciences\| PubMed ID: 39000138	2024
Harnessing Non-Antibiotic Strategies to Counter Multidrug-Resistant Clinical Pathogens with Special Reference to Antimicrobial Peptides and Their Coatings. Antibiotics (Basel, Switzerland)\| PubMed ID: 39858343	2025
Synergistic effects of peptide mimics against enveloped viruses. Virology\| PubMed ID: 40483733	2025
A review of technological advances in the management of bacterial, fungal, viral, and keratitis. Clinical & experimental optometry\| PubMed ID: 41242874	2025

Umme Laila Urmi

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