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Recent Therapeutic Strategies against Infectious Agents
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Recent Therapeutic Strategies against Infectious Agents

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: closed (15 November 2023) | Viewed by 7321

Special Issue Editors

Dr. Fiorella Meneghetti

E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, University of Milan, Via L. Mangiagalli 25, 20133 Milano, Italy
Interests: diffraction techniques; structure elucidation; conformation of bioactive compounds; antitubercular and anticancer agents; metal complexes, protein–protein interaction inhibitors; enzymatic inhibitors; multi-target drugs
Special Issues, Collections and Topics in MDPI journals
Dr. Matteo Mori

E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, University of Milan, Via L. Mangiagalli 25, 20133 Milano, Italy
Interests: diffraction techniques; structure elucidation; conformation of bioactive compounds; antitubercular and anticancer agents; metal complexes, protein–protein interaction inhibitors; enzymatic inhibitors; multi-target drugs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Infectious diseases still account for a substantial proportion of deaths worldwide. The plague of antimicrobial resistance represents an alarming signal for both human and animal healthcare, making the search for novel classes of antibiotics necessary to replenish our arsenal of antibacterial drugs. In addition, the tremendous impact exerted by viral infections and related pathologies on our lives recently has forced scientists to acknowledge the opportunities and challenges associated with tackling infectious diseases by developing effective antiviral agents endowed with novel mechanisms of action. The discovery of new antimicrobial/antiviral agents, as well as the repurposing of existing drugs, will be crucial to fight the ever-increasing resistance of “superbugs”, pathogenic fungi, viruses, and parasites.

The International Journal of Molecular Sciences invites both reviews and original articles, which highlight the recent medicinal chemistry research on novel antibacterial/antiviral agents. Topics, including natural product screening, identification and validation of new antibacterial/antiviral targets, and strategies for the discovery and optimization of the compounds, are all welcomed.

Dr. Fiorella Meneghetti
Dr. Matteo Mori
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • small molecules
  • peptides
  • peptidomimetics
  • bacterial infections
  • fungi
  • viruses
  • parasites
  • drug design
  • computational tools
  • biological assays
  • resistance mechanisms

Published Papers (6 papers)

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Research

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17 pages, 1756 KiB  
Article
Suppression of Borna Disease Virus Replication during Its Persistent Infection Using the CRISPR/Cas13b System
by Shigenori Sasaki, Hirohito Ogawa, Hirokazu Katoh and Tomoyuki Honda
Int. J. Mol. Sci. 2024, 25(6), 3523; https://doi.org/10.3390/ijms25063523 - 20 Mar 2024
Viewed by 633
Abstract
Borna disease virus (BoDV-1) is a bornavirus that infects the central nervous systems of various animal species, including humans, and causes fatal encephalitis. BoDV-1 also establishes persistent infection in neuronal cells and causes neurobehavioral abnormalities. Once neuronal cells or normal neural networks are [...] Read more.
Borna disease virus (BoDV-1) is a bornavirus that infects the central nervous systems of various animal species, including humans, and causes fatal encephalitis. BoDV-1 also establishes persistent infection in neuronal cells and causes neurobehavioral abnormalities. Once neuronal cells or normal neural networks are lost by BoDV-1 infection, it is difficult to regenerate damaged neural networks. Therefore, the development of efficient anti-BoDV-1 treatments is important to improve the outcomes of the infection. Recently, one of the clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) systems, CRISPR/Cas13, has been utilized as antiviral tools. However, it is still unrevealed whether the CRISPR/Cas13 system can suppress RNA viruses in persistently infected cells. In this study, we addressed this question using persistently BoDV-1-infected cells. The CRISPR/Cas13 system targeting viral mRNAs efficiently decreased the levels of target viral mRNAs and genomic RNA (gRNA) in persistently infected cells. Furthermore, the CRISPR/Cas13 system targeting viral mRNAs also suppressed BoDV-1 infection if the system was introduced prior to the infection. Collectively, we demonstrated that the CRISPR/Cas13 system can suppress BoDV-1 in both acute and persistent infections. Our findings will open the avenue to treat prolonged infection with RNA viruses using the CRISPR/Cas13 system. Full article
(This article belongs to the Special Issue Recent Therapeutic Strategies against Infectious Agents)
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12 pages, 1823 KiB  
Article
A Comprehensive Technology Platform for the Rapid Discovery of Peptide Inhibitors against SARS-CoV-2 Pseudovirus Infection
by Marten Beeg, Sara Baroni, Arianna Piotti, Alessia Porta, Ada De Luigi, Alfredo Cagnotto, Marco Gobbi, Luisa Diomede and Mario Salmona
Int. J. Mol. Sci. 2023, 24(15), 12146; https://doi.org/10.3390/ijms241512146 - 29 Jul 2023
Viewed by 1178
Abstract
We developed and validated a technology platform for designing and testing peptides inhibiting the infectivity of SARS-CoV-2 spike protein-based pseudoviruses. This platform integrates target evaluation, in silico inhibitor design, peptide synthesis, and efficacy screening. We generated a cyclic peptide library derived from the [...] Read more.
We developed and validated a technology platform for designing and testing peptides inhibiting the infectivity of SARS-CoV-2 spike protein-based pseudoviruses. This platform integrates target evaluation, in silico inhibitor design, peptide synthesis, and efficacy screening. We generated a cyclic peptide library derived from the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and the angiotensin-converting enzyme 2 (ACE2) receptor. The cell-free validation process by ELISA competition assays and Surface Plasmon Resonance (SPR) studies revealed that the cyclic peptide c9_05, but not its linear form, binds well to ACE2. Moreover, it effectively inhibited the transduction in HEK293, stably expressing the human ACE2 receptor of pseudovirus particles displaying the SARS-CoV-2 spike in the Wuhan or UK variants. However, the inhibitory efficacy of c9_05 was negligible against the Omicron variant, and it failed to impede the entry of pseudoviruses carrying the B.1.351 (South African) spike. These variants contain three or more mutations known to increase affinity to ACE2. This suggests further refinement is needed for potential SARS-CoV-2 inhibition. Our study hints at a promising approach to develop inhibitors targeting viral infectivity receptors, including SARS-CoV-2’s. This platform also promises swift identification and evaluation of inhibitors for other emergent viruses. Full article
(This article belongs to the Special Issue Recent Therapeutic Strategies against Infectious Agents)
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15 pages, 3827 KiB  
Article
Sustained Release of Antifungal and Antibacterial Agents from Novel Hybrid Degradable Nanofibers for the Treatment of Polymicrobial Osteomyelitis
by Yung-Heng Hsu, Yi-Hsun Yu, Ying-Chao Chou, Chia-Jung Lu, Yu-Ting Lin, Steve Wen-Neng Ueng and Shih-Jung Liu
Int. J. Mol. Sci. 2023, 24(4), 3254; https://doi.org/10.3390/ijms24043254 - 07 Feb 2023
Cited by 3 | Viewed by 1345
Abstract
This study aimed to develop a drug delivery system with hybrid biodegradable antifungal and antibacterial agents incorporated into poly lactic-co-glycolic acid (PLGA) nanofibers, facilitating an extended release of fluconazole, vancomycin, and ceftazidime to treat polymicrobial osteomyelitis. The nanofibers were assessed using scanning electron [...] Read more.
This study aimed to develop a drug delivery system with hybrid biodegradable antifungal and antibacterial agents incorporated into poly lactic-co-glycolic acid (PLGA) nanofibers, facilitating an extended release of fluconazole, vancomycin, and ceftazidime to treat polymicrobial osteomyelitis. The nanofibers were assessed using scanning electron microscopy, tensile testing, water contact angle analysis, differential scanning calorimetry, and Fourier-transform infrared spectroscopy. The in vitro release of the antimicrobial agents was assessed using an elution method and a high-performance liquid chromatography assay. The in vivo elution pattern of nanofibrous mats was assessed using a rat femoral model. The experimental results demonstrated that the antimicrobial agent-loaded nanofibers released high levels of fluconazole, vancomycin, and ceftazidime for 30 and 56 days in vitro and in vivo, respectively. Histological assays revealed no notable tissue inflammation. Therefore, hybrid biodegradable PLGA nanofibers with a sustainable release of antifungal and antibacterial agents may be employed for the treatment of polymicrobial osteomyelitis. Full article
(This article belongs to the Special Issue Recent Therapeutic Strategies against Infectious Agents)
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Review

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19 pages, 675 KiB  
Review
Human–Fungal Pathogen Interactions from the Perspective of Immunoproteomics Analyses
by Tanaporn Wangsanut and Monsicha Pongpom
Int. J. Mol. Sci. 2024, 25(6), 3531; https://doi.org/10.3390/ijms25063531 - 20 Mar 2024
Viewed by 508
Abstract
Antibody immunity is now known to play a critical role in combating mycotic infections. The identification of molecules that can elicit an antibody response against fungal pathogens is the first step in developing antibody-based therapeutic strategies. Antigenic proteins are molecules recognized by the [...] Read more.
Antibody immunity is now known to play a critical role in combating mycotic infections. The identification of molecules that can elicit an antibody response against fungal pathogens is the first step in developing antibody-based therapeutic strategies. Antigenic proteins are molecules recognized by the immune system that can stimulate antibody production and, therefore, can be a direct target for studying human–fungal pathogen interactions. Advances in recent immunoproteomic approaches have substantially aided in determining the key antigenic proteins on a large scale. In this review, we present a collection of antigenic proteins identified in yeast, dimorphic, and filamentous fungal pathogens to date. The general features of antigenic proteins are summarized and reveal that the proteins could commonly function in antistress responses, protein synthesis, and metabolism. The antigenic proteins listed here could serve as starting materials for developing species-specific or broad-spectrum diagnostic tests, therapeutic antibodies, and even vaccines against fungal infections. Full article
(This article belongs to the Special Issue Recent Therapeutic Strategies against Infectious Agents)
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25 pages, 9467 KiB  
Review
Development of Fluorescence-Based Assays for Key Viral Proteins in the SARS-CoV-2 Infection Process and Lifecycle
by Mingzhenlong Deng, Chuang Zhang, Wanli Yan, Lei Chen, Bin He and Yan Li
Int. J. Mol. Sci. 2024, 25(5), 2850; https://doi.org/10.3390/ijms25052850 - 01 Mar 2024
Viewed by 1198
Abstract
Since the appearance of SARS-CoV-2 in 2019, the ensuing COVID-19 (Corona Virus Disease 2019) pandemic has posed a significant threat to the global public health system, human health, life, and economic well-being. Researchers worldwide have devoted considerable efforts to curb its spread and [...] Read more.
Since the appearance of SARS-CoV-2 in 2019, the ensuing COVID-19 (Corona Virus Disease 2019) pandemic has posed a significant threat to the global public health system, human health, life, and economic well-being. Researchers worldwide have devoted considerable efforts to curb its spread and development. The latest studies have identified five viral proteins, spike protein (Spike), viral main protease (3CLpro), papain-like protease (PLpro), RNA-dependent RNA polymerase (RdRp), and viral helicase (Helicase), which play crucial roles in the invasion of SARS-CoV-2 into the human body and its lifecycle. The development of novel anti-SARS-CoV-2 drugs targeting these five viral proteins holds immense promise. Therefore, the development of efficient, high-throughput screening methodologies specifically designed for these viral proteins is of utmost importance. Currently, a plethora of screening techniques exists, with fluorescence-based assays emerging as predominant contenders. In this review, we elucidate the foundational principles and methodologies underpinning fluorescence-based screening approaches directed at these pivotal viral targets, hoping to guide researchers in the judicious selection and refinement of screening strategies, thereby facilitating the discovery and development of lead compounds for anti-SARS-CoV-2 pharmaceuticals. Full article
(This article belongs to the Special Issue Recent Therapeutic Strategies against Infectious Agents)
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17 pages, 345 KiB  
Review
Medical Device-Associated Healthcare Infections: Sterilization and the Potential of Novel Biological Approaches to Ensure Patient Safety
by Mary Garvey
Int. J. Mol. Sci. 2024, 25(1), 201; https://doi.org/10.3390/ijms25010201 - 22 Dec 2023
Cited by 2 | Viewed by 1649
Abstract
Healthcare-associated infections caused by multi-drug-resistant pathogens are increasing globally, and current antimicrobial options have limited efficacy against these robust species. The WHO details the critically important bacterial and fungal species that are often associated with medical device HAIs. The effective sterilization of medical [...] Read more.
Healthcare-associated infections caused by multi-drug-resistant pathogens are increasing globally, and current antimicrobial options have limited efficacy against these robust species. The WHO details the critically important bacterial and fungal species that are often associated with medical device HAIs. The effective sterilization of medical devices plays a key role in preventing infectious disease morbidity and mortality. A lack of adherence to protocol and limitations associated with each sterilization modality, however, allows for the incidence of disease. Furthermore, issues relating to carcinogenic emissions from ethylene oxide gas (EtO) have motivated the EPA to propose limiting EtO use or seeking alternative sterilization methods for medical devices. The Food and Drug Administration supports the sterilization of healthcare products using low-temperature VH2O2 as an alternative to EtO. With advances in biomaterial and medical devices and the increasing use of combination products, current sterilization modalities are becoming limited. Novel approaches to disinfection and sterilization of medical devices, biomaterials, and therapeutics are warranted to safeguard public health. Bacteriophages, endolysins, and antimicrobial peptides are considered promising options for the prophylactic and meta-phylactic control of infectious diseases. This timely review discusses the application of these biologics as antimicrobial agents against critically important WHO pathogens, including ESKAPE bacterial species. Full article
(This article belongs to the Special Issue Recent Therapeutic Strategies against Infectious Agents)
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