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Molecular Medicine Applications in Infectious Diseases: Latest Innovations

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

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 15218

Special Issue Editor

Department of Applied Ecology, Faculty of Environmental Sciences, Czech University of Life Sciences Prague, Kamýcká 129, 165 00 Prague, Czech Republic
Interests: infectious diseases; pharmacology and toxicology of natural products; analytical methods for isolation and identification of natural products; molecular mechanisms of pharmacological action; pediatric infectious diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

For decades, effective treatments of infectious diseases such as viral, bacterial, and fungal infections have remained a strong challenge in medicine. As we know, healthcare providers and researchers are currently facing many hurdles to finding effective therapies for these diseases, including drug resistance, which is considered a major challenge. In recent years, molecular medicine evolution has accelerated the progress of finding successful approaches to manage infectious diseases. Therefore, this Special Issue aims to shed light on recent innovations that explain infectious disease pathogenesis at the molecular or physiological level, which may lead to the design of specific tools for disease diagnosis, treatment (including drug design and development), or prevention (including vaccine development). Studies that are performed at cellular and genetic levels, which describe the implications of the results for infectious diseases, are also considered for publication. Computational investigations that are performed to unveil the molecular pathways and are supported by in vitro and in vivo experiments are also welcomed.

Dr. Sherif T.S. Hassan
Guest Editor

Manuscript Submission Information

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Keywords

  • Bacterial infections
  • Fungal infections
  • Viral infections
  • Infectious microorganisms
  • Molecular medicine techniques
  • Diagnosis, treatment, and prevention approaches
  • Molecular and physiological investigations
  • Cellular and genetic studies
  • Disease pathogenesis
  • Computational methods
  • Drug design and development

Published Papers (7 papers)

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Editorial

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4 pages, 196 KiB  
Editorial
Editorial of the Special Issue “Molecular Medicine Applications in Infectious Diseases: Latest Innovations”
by Sherif T. S. Hassan
Int. J. Mol. Sci. 2023, 24(21), 15899; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms242115899 - 02 Nov 2023
Viewed by 467
Abstract
The integration of molecular approaches in medicine allows for a more precise understanding of the mechanisms underlying infectious diseases, paving the way for targeted therapies, personalized medicine, and the development of new diagnostic tools [...] Full article

Research

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14 pages, 1618 KiB  
Article
Analytical Assessment of the Vela Diagnostics NGS Assay for HIV Genotyping and Resistance Testing: The Apulian Experience
by Maria Addolorata Bonifacio, Chiara Genchi, Antonella Lagioia, Vincenza Talamo, Anna Volpe and Maria Addolorata Mariggiò
Int. J. Mol. Sci. 2022, 23(5), 2727; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23052727 - 01 Mar 2022
Cited by 6 | Viewed by 2922
Abstract
Drug-resistance monitoring is one of the hardest challenges in HIV management. Next-generation sequencing (NGS) technologies speed up the detection of drug resistance, allowing the adjustment of antiretroviral therapy and enhancing the quality of life of people living with HIV. Recently, the NGS Sentosa [...] Read more.
Drug-resistance monitoring is one of the hardest challenges in HIV management. Next-generation sequencing (NGS) technologies speed up the detection of drug resistance, allowing the adjustment of antiretroviral therapy and enhancing the quality of life of people living with HIV. Recently, the NGS Sentosa® SQ HIV Genotyping Assay (Vela Diagnostics) received approval for in vitro diagnostics use. This work is the first Italian evaluation of the performance of the Vela Diagnostics NGS platform, assessed with 420 HIV-1 clinical samples. A comparison with Sanger sequencing performance is also reported, highlighting the advantages and disadvantages of the Sentosa® NGS assay. The precision of the technology was studied with reference specimens, while intra- and inter-assay reproducibility were evaluated for selected clinical samples. Vela Diagnostics’ NGS assay reached an 87% success rate through 30 runs of analysis in a real-world clinical context. The concordance with Sanger sequencing outcomes was equal to 97.2%. Several detected mismatches were due to NGS’s superior sensitivity to low-frequency variants. A high accuracy was observed in testing reference samples. Repeatability and reproducibility assays highlighted the good performance of the NGS platform. Beyond a few technical issues that call for further optimization, the key improvement will be a better balance between costs and processing speed. Once these issues have been solved, the Sentosa® SQ HIV Genotyping Assay will be the way forward for HIV resistance testing. Full article
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12 pages, 8996 KiB  
Article
Bifunctional Inhibitors of Influenza Virus Neuraminidase: Molecular Design of a Sulfonamide Linker
by Sergei Evteev, Dmitry Nilov, Aleksandra Polenova and Vytas Švedas
Int. J. Mol. Sci. 2021, 22(23), 13112; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222313112 - 03 Dec 2021
Cited by 6 | Viewed by 2095
Abstract
The growing resistance of the influenza virus to widely used competitive neuraminidase inhibitors occupying the active site of the enzyme requires the development of bifunctional compounds that can simultaneously interact with other regulatory sites on the protein surface. When developing such an inhibitor [...] Read more.
The growing resistance of the influenza virus to widely used competitive neuraminidase inhibitors occupying the active site of the enzyme requires the development of bifunctional compounds that can simultaneously interact with other regulatory sites on the protein surface. When developing such an inhibitor and combining structural fragments that could be located in the sialic acid cavity of the active site and the adjacent 430-cavity, it is necessary to select a suitable linker not only for connecting the fragments, but also to ensure effective interactions with the unique arginine triad Arg118-Arg292-Arg371 of neuraminidase. Using molecular modeling, we have demonstrated the usefulness of the sulfonamide group in the linker design and the potential advantage of this functional group over other isosteric analogues. Full article
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19 pages, 5216 KiB  
Article
In Leishmania major, the Homolog of the Oncogene PES1 May Play a Critical Role in Parasite Infectivity
by Miriam Algarabel, Celia Fernández-Rubio, Katerina Musilova, José Peña-Guerrero, Andrés Vacas, Esther Larrea and Paul A. Nguewa
Int. J. Mol. Sci. 2021, 22(22), 12592; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212592 - 22 Nov 2021
Cited by 5 | Viewed by 1796
Abstract
Leishmaniasis is a neglected tropical disease caused by Leishmania spp. The improvement of existing treatments and the discovery of new drugs remain ones of the major goals in control and eradication of this disease. From the parasite genome, we have identified the homologue [...] Read more.
Leishmaniasis is a neglected tropical disease caused by Leishmania spp. The improvement of existing treatments and the discovery of new drugs remain ones of the major goals in control and eradication of this disease. From the parasite genome, we have identified the homologue of the human oncogene PES1 in Leishmania major (LmjPES). It has been demonstrated that PES1 is involved in several processes such as ribosome biogenesis, cell proliferation and genetic transcription. Our phylogenetic studies showed that LmjPES encodes a highly conserved protein containing three main domains: PES N-terminus (shared with proteins involved in ribosomal biogenesis), BRCT (found in proteins related to DNA repair processes) and MAEBL-type domain (C-terminus, related to erythrocyte invasion in apicomplexan). This gene showed its highest expression level in metacyclic promastigotes, the infective forms; by fluorescence microscopy assay, we demonstrated the nuclear localization of LmjPES protein. After generating mutant parasites overexpressing LmjPES, we observed that these clones displayed a dramatic increase in the ratio of cell infection within macrophages. Furthermore, BALB/c mice infected with these transgenic parasites exhibited higher footpad inflammation compared to those inoculated with non-overexpressing parasites. Full article
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Review

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20 pages, 3311 KiB  
Review
Molecular Mechanisms of Flavonoids against Tumor Gamma-Herpesviruses and Their Correlated Cancers—A Focus on EBV and KSHV Life Cycles and Carcinogenesis
by Sherif T. S. Hassan and Miroslava Šudomová
Int. J. Mol. Sci. 2023, 24(1), 247; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24010247 - 23 Dec 2022
Cited by 6 | Viewed by 2013
Abstract
Epstein–Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) are cancer-causing viruses that belong to human gamma-herpesviruses. They are DNA viruses known to establish lifelong infections in humans, with the ability to develop various types of cancer. Drug resistance remains the main barrier to [...] Read more.
Epstein–Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) are cancer-causing viruses that belong to human gamma-herpesviruses. They are DNA viruses known to establish lifelong infections in humans, with the ability to develop various types of cancer. Drug resistance remains the main barrier to achieving effective therapies for viral infections and cancer. Thus, new medications with dual antiviral and anticancer actions are highly needed. Flavonoids are secondary metabolites biosynthesized by plants with diverse therapeutic effects on human health. In this review, we feature the potential role of flavonoids (flavones, protoflavones, isoflavones, flavanones, flavonols, dihydroflavonols, catechins, chalcones, anthocyanins, and other flavonoid-type compounds) in controlling gamma-herpesvirus-associated cancers by blocking EBV and KSHV infections and inhibiting the formation and growth of the correlated tumors, such as nasopharyngeal carcinoma, Burkitt’s lymphoma, gastric cancer, extranodal NK/T-cell lymphoma, squamous cell carcinoma, Kaposi sarcoma, and primary effusion lymphoma. The underlying mechanisms via targeting EBV and KSHV life cycles and carcinogenesis are highlighted. Moreover, the effective concentrations or doses are emphasized. Full article
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21 pages, 2203 KiB  
Review
Insights into Antiviral Properties and Molecular Mechanisms of Non-Flavonoid Polyphenols against Human Herpesviruses
by Sherif T. S. Hassan, Miroslava Šudomová, Alena Mazurakova and Peter Kubatka
Int. J. Mol. Sci. 2022, 23(22), 13891; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232213891 - 11 Nov 2022
Cited by 7 | Viewed by 2429
Abstract
Herpesviruses are one of the most contagious DNA viruses that threaten human health, causing severe diseases, including, but not limited to, certain types of cancer and neurological complications. The overuse and misuse of anti-herpesvirus drugs are key factors leading to drug resistance. Therefore, [...] Read more.
Herpesviruses are one of the most contagious DNA viruses that threaten human health, causing severe diseases, including, but not limited to, certain types of cancer and neurological complications. The overuse and misuse of anti-herpesvirus drugs are key factors leading to drug resistance. Therefore, targeting human herpesviruses with natural products is an attractive form of therapy, as it might improve treatment efficacy in therapy-resistant herpesviruses. Plant polyphenols are major players in the health arena as they possess diverse bioactivities. Hence, in this article, we comprehensively summarize the recent advances that have been attained in employing plant non-flavonoid polyphenols, such as phenolic acids, tannins and their derivatives, stilbenes and their derivatives, lignans, neolignans, xanthones, anthraquinones and their derivatives, curcuminoids, coumarins, furanocoumarins, and other polyphenols (phloroglucinol) as promising anti-herpesvirus drugs against various types of herpesvirus such as alpha-herpesviruses (herpes simplex virus type 1 and 2 and varicella-zoster virus), beta-herpesviruses (human cytomegalovirus), and gamma-herpesviruses (Epstein–Barr virus and Kaposi sarcoma-associated herpesvirus). The molecular mechanisms of non-flavonoid polyphenols against the reviewed herpesviruses are also documented. Full article
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16 pages, 1269 KiB  
Review
The Roles of NOD-like Receptors in Innate Immunity in Otitis Media
by Myung-Won You, Dokyoung Kim, Eun-Hye Lee, Dong-Choon Park, Jae-Min Lee, Dae-Woong Kang, Sang-Hoon Kim and Seung-Geun Yeo
Int. J. Mol. Sci. 2022, 23(4), 2350; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23042350 - 21 Feb 2022
Viewed by 2186
Abstract
Acute otitis media (AOM) can persist or lead to various complications in individuals in which the innate immune system is impaired. In this context, impaired expression of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR), an intracellular pathogen-recognition receptor (PRR), is involved in the etiology [...] Read more.
Acute otitis media (AOM) can persist or lead to various complications in individuals in which the innate immune system is impaired. In this context, impaired expression of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR), an intracellular pathogen-recognition receptor (PRR), is involved in the etiology of OM in humans and animals, affecting its development, severity, chronicity, recurrence, and associated complications. To assess this relationship, we reviewed literature reports relating NLR expression patterns with the pathophysiology and clinical features of OM in the larger context of impaired innate immunity. We summarized the results of published studies on the expression of NLRs in animals and humans in acute otitis media (AOM), otitis media with effusion (OME), chronic otitis media (COM) with cholesteatoma, and COM without cholesteatoma. NLRs were expressed mainly in association with bacterial infection in AOM, OME, COM with cholesteatoma, and COM without cholesteatoma. In addition, expression of NLRs was affected by the presence or absence of bacteria, fluid characteristics, disease recurrence, tissue type, and repeated surgery. Various factors of the innate immune system are involved in the pathogenesis of OM in the middle ear. NLRs are expressed in AOM, OME, COM with cholesteatoma, and COM without cholesteatoma. Impaired NLR expression induced the development, chronicity and recurrence of OM and exacerbated associated complications, indicating that NLRs have important roles in the pathogenesis of OM. Full article
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