Editorial

2 pages, 163 KiB

Open AccessEditorial

by Ali Zarrabi, Fabrizio Caldera and Francesco Trotta

Int. J. Mol. Sci. 2023, 24(4), 3295; https://doi.org/10.3390/ijms24043295 - 07 Feb 2023

Cited by 1 | Viewed by 908

The COVID-19 pandemic showed the crucial significance of investing in and conducting research on infectious diseases [...] Full article

(This article belongs to the Special Issue Materials for Infectious Diseases)

Research

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11 pages, 3020 KiB

Open AccessArticle

Kinetics of Immunolatex Deposition at Abiotic Surfaces under Flow Conditions: Towards Quantitative Agglutination Assays

by Paulina Żeliszewska, Jolanta Szych, Monika Wasilewska and Zbigniew Adamczyk

Int. J. Mol. Sci. 2023, 24(1), 692; https://doi.org/10.3390/ijms24010692 - 30 Dec 2022

Cited by 3 | Viewed by 1291

Abstract

Physicochemical properties of immunolatex, prepared by incubation of negatively charged polystyrene microparticles with polyclonal rabbit IgGs, were determined by a variety of experimental techniques. These comprised dynamic light scattering (DLS), laser Doppler velocimetry (LDV) and atomic force microscopy (AFM). The particle diffusion coefficient, [...] Read more.

Physicochemical properties of immunolatex, prepared by incubation of negatively charged polystyrene microparticles with polyclonal rabbit IgGs, were determined by a variety of experimental techniques. These comprised dynamic light scattering (DLS), laser Doppler velocimetry (LDV) and atomic force microscopy (AFM). The particle diffusion coefficient, the hydrodynamic diameter, the electrophoretic mobility, the zeta potential and the suspension stability were determined as a function of pH for different ionic strengths. The deposition of the immunolatex on bare and polyallylamine (PAH) functionalized mica was investigated using the microfluidic oblique impinging-jet cell, with an in situ, real-time image analysis module. The particle deposition kinetics was acquired by a direct particle enumeration procedure. The measurements enabled us to determine the range of pH where the specific deposition of the immunolatex on these substrates was absent. We argue that the obtained results have practical significance for conducting efficient flow immunoassays governed by specific antigen/antibody interactions. Full article

(This article belongs to the Special Issue Materials for Infectious Diseases)

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16 pages, 2667 KiB

Open AccessArticle

Identification of a βCD-Based Hyper-Branched Negatively Charged Polymer as HSV-2 and RSV Inhibitor

by Rachele Francese, Claudio Cecone, Matteo Costantino, Gjylije Hoti, Pierangiola Bracco, David Lembo and Francesco Trotta

Int. J. Mol. Sci. 2022, 23(15), 8701; https://doi.org/10.3390/ijms23158701 - 04 Aug 2022

Cited by 3 | Viewed by 1806

Abstract

Cyclodextrins and cyclodextrin derivatives were demonstrated to improve the antiviral potency of numerous drugs, but also to be endowed with intrinsic antiviral action. They are suitable building blocks for the synthesis of functionalized polymer structures with potential antiviral activity. Accordingly, four water-soluble hyper-branched [...] Read more.

Cyclodextrins and cyclodextrin derivatives were demonstrated to improve the antiviral potency of numerous drugs, but also to be endowed with intrinsic antiviral action. They are suitable building blocks for the synthesis of functionalized polymer structures with potential antiviral activity. Accordingly, four water-soluble hyper-branched beta cyclodextrin (βCD)-based anionic polymers were screened against herpes simplex virus (HSV-2), respiratory syncytial virus (RSV), rotavirus (HRoV), and influenza virus (FluVA). They were characterized by FTIR-ATR, TGA, elemental analyses, zeta-potential measurements, and potentiometric titrations, while the antiviral activity was investigated with specific in vitro assays. The polymer with the highest negative charge, pyromellitic dianhydride-linked polymer (P_PMDA), showed significant antiviral action against RSV and HSV-2, by inactivating RSV free particles and by altering HSV-2 binding to the cell. The polymer fraction with the highest molecular weight showed the strongest antiviral activity and both P_PMDA and its active fractions were not toxic for cells. Our results suggest that the polymer virucidal activity against RSV can be exploited to produce new antiviral materials to counteract the virus dissemination through the air or direct contact. Additionally, the strong HSV-2 binding inhibition along with the water solubility of P_PMDA and the acyclovir complexation potential of βCD are attractive features for developing new therapeutic topical options against genital HSV-2 infection. Full article

(This article belongs to the Special Issue Materials for Infectious Diseases)

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14 pages, 3674 KiB

Open AccessArticle

Antimicrobial Efficacy and Permeability of Various Sealing Materials in Two Different Types of Implant–Abutment Connections

by Igor Smojver, Roko Bjelica, Marko Vuletić, Dražena Gerbl, Ana Budimir and Dragana Gabrić

Int. J. Mol. Sci. 2022, 23(14), 8031; https://doi.org/10.3390/ijms23148031 - 21 Jul 2022

Cited by 3 | Viewed by 1587

Abstract

The presence of a microgap along an implant–abutment connection (IAC) is considered the main disadvantage of two-piece implant systems. Its existence may lead to mechanical and biological complications. Different IAC designs have been developed to minimise microleakage through the microgap and to increase [...] Read more.

The presence of a microgap along an implant–abutment connection (IAC) is considered the main disadvantage of two-piece implant systems. Its existence may lead to mechanical and biological complications. Different IAC designs have been developed to minimise microleakage through the microgap and to increase the stability of prosthodontic abutments. Furthermore, different sealing materials have appeared on the market to seal the gap at the IAC. The purpose of this study was to evaluate the antimicrobial efficacy and permeability of different materials designed to seal the microgap, and their behaviour in conical and straight types of internal IACs. One hundred dental implants with original prosthodontic abutments were divided into two groups of fifty implants according to the type of IAC. Three different sealing materials (GapSeal, Flow.sil, and Oxysafe gel) were applied in the test subgroups. The contamination of implant–abutment assemblies was performed by a joint suspension containing Candida albicans and Staphylococcus aureus. It was concluded that the IAC type had no significant influence on microleakage regarding microbial infection. No significant difference was found between the various sealing agents. Only one sealing agent (GapSeal) was found to significantly prevent microleakage. A complete hermetic seal was not achieved with any of the sealing agents tested in this study. Full article

(This article belongs to the Special Issue Materials for Infectious Diseases)

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15 pages, 2096 KiB

Open AccessArticle

Ascorbic Acid as an Adjuvant to Unbleached Cotton Promotes Antimicrobial Activity in Spunlace Nonwovens

by Judson Vincent Edwards, Nicolette T. Prevost, Dorne Yager, Robert Mackin, Michael Santiago, SeChin Chang, Brian Condon and Joseph Dacorta

Int. J. Mol. Sci. 2022, 23(7), 3598; https://doi.org/10.3390/ijms23073598 - 25 Mar 2022

Cited by 4 | Viewed by 2038

Abstract

The development of affordable, effective, and environmentally friendly barrier fabrics is a current goal in antimicrobial textile development. The discovery of new routes to achieve non-toxic naturally occurring molecules with antimicrobial activity is of interest in the development of materials that promote wound [...] Read more.

The development of affordable, effective, and environmentally friendly barrier fabrics is a current goal in antimicrobial textile development. The discovery of new routes to achieve non-toxic naturally occurring molecules with antimicrobial activity is of interest in the development of materials that promote wound healing, improve hygiene, and offer protection against nosocomial infection. Highly cleaned and sterile unbleached cotton has constituents that produce hydrogen peroxide at levels commensurate with those that favor cell signaling in wound healing. Here, we show the antimicrobial and antiviral properties of spunlaced griege cotton-containing nonwovens treated with ascorbic acid formulations. The mechanism of action occurs through the promotion of enhanced hydrogen peroxide activity. The levels of hydrogen peroxide activity afford antimicrobial activity against Gram-negative and Gram-positive bacteria and antiviral activity against MS2 bacteriophages. Spun-bond nonwoven unbleached cotton was treated with ascorbic acid using traditional pad-dry-cure methods. An assessment of antibacterial and antiviral activity against Staphylococcus aureus, Klebsiella pneumoniae, and MS2 bacteriophages with the AATCC 100 test method showed a 99.99% inhibitory activity. An approach to the covalent attachment of ascorbic to cellulose through citric acid crosslinking chemistry is also discussed. Thus, a simple, low-cost approach to antimicrobial and antiviral cotton-based nonwovens applicable to dressings, nosocomial barrier fabrics, and face masks can be adopted by combining ascorbic acid with spunlace greige cotton nonwoven fabrics. Full article

(This article belongs to the Special Issue Materials for Infectious Diseases)

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16 pages, 2610 KiB

Open AccessArticle

Detection of Human Neutrophil Elastase by Fluorescent Peptide Sensors Conjugated to TEMPO-Oxidized Nanofibrillated Cellulose

by Robert T. Mackin, Krystal R. Fontenot, Judson Vincent Edwards, Nicolette T. Prevost, Jacobs H. Jordan, Michael W. Easson, Brian D. Condon and Alfred D. French

Int. J. Mol. Sci. 2022, 23(6), 3101; https://doi.org/10.3390/ijms23063101 - 13 Mar 2022

Cited by 7 | Viewed by 2150

Abstract

Peptide–cellulose conjugates designed for use as optical protease sensors have gained interest for point-of-care (POC) detection. Elevated serine protease levels are often found in patients with chronic illnesses, necessitating optimal biosensor design for POC assessment. Nanocellulose provides a platform for protease sensors as [...] Read more.

Peptide–cellulose conjugates designed for use as optical protease sensors have gained interest for point-of-care (POC) detection. Elevated serine protease levels are often found in patients with chronic illnesses, necessitating optimal biosensor design for POC assessment. Nanocellulose provides a platform for protease sensors as a transducer surface, and the employment of nanocellulose in this capacity combines its biocompatibility and high specific surface area properties to confer sensitive detection of dilute biomarkers. However, a basic understanding of the spatiotemporal relationships of the transducer surface and sensor disposition is needed to improve protease sensor design and development. Here, we examine a tripeptide, fluorogenic elastase biosensor attached to TEMPO-oxidized nanofibrillated cellulose via a polyethylene glycol linker. The synthetic conjugate was found to be active in the presence of human neutrophil elastase at levels comparable to other cellulose-based biosensors. Computational models examined the relationship of the sensor molecule to the transducer surface. The results illustrate differences in two crystallite transducer surfaces ((110) vs. (1−10)) and reveal preferred orientations of the sensor. Finally, a determination of the relative (110) vs. (1−10) orientations of crystals extracted from cotton demonstrates a preference for the (1−10) conformer. This model study potentiates the HNE sensor results for enhanced sensor activity design. Full article

(This article belongs to the Special Issue Materials for Infectious Diseases)

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23 pages, 6159 KiB

Open AccessArticle

Cationic Phenosafranin Photosensitizers Based on Polyhedral Oligomeric Silsesquioxanes for Inactivation of Gram-Positive and Gram-Negative Bacteria

by Krystyna Rozga-Wijas, Irena Bak-Sypien, Katarzyna Turecka, Magdalena Narajczyk and Krzysztof Waleron

Int. J. Mol. Sci. 2021, 22(24), 13373; https://doi.org/10.3390/ijms222413373 - 13 Dec 2021

Cited by 5 | Viewed by 2091

Abstract

The high photodynamic effect of the Newman strain of the S. aureus and of clinical strains of S. aureus MRSA 12673 and E. coli 12519 are observed for new cationic light-activated phenosafranin polyhedral oligomeric silsesquioxane (POSS) conjugates in vitro. Killing of bacteria was [...] Read more.

The high photodynamic effect of the Newman strain of the S. aureus and of clinical strains of S. aureus MRSA 12673 and E. coli 12519 are observed for new cationic light-activated phenosafranin polyhedral oligomeric silsesquioxane (POSS) conjugates in vitro. Killing of bacteria was achieved at low concentrations of silsesquioxanes (0.38 µM) after light irradiation (λ_{em. max} = 522 nm, 10.6 mW/cm²) for 5 min. Water-soluble POSS-photosensitizers are synthesized by chemically coupling a phenosafranin dye (PSF) (3,7-diamino-5-phenylphenazine chloride) to an inorganic silsesquioxane cage activated by attachment of succinic anhydride rings. The chemical structure of conjugates is confirmed by ¹H, ¹³C NMR, HRMS, IR, fluorescence spectroscopy and UV-VIS analyzes. The APDI and daunorubicin (DAU) synergy is investigated for POSSPSFDAU conjugates. Confocal microscopy experiments indicate a site of intracellular accumulation of the POSSPSF, whereas iBuPOSSPSF and POSSPSFDAU accumulate in the cell wall or cell membrane. Results from the TEM study show ruptured S. aureus cells with leaking cytosolic mass and distorted cells of E. coli. Bacterial cells are eradicated by ROS produced upon irradiation of the covalent conjugates that can kill the bacteria by destruction of cellular membranes, intracellular proteins and DNA through the oxidative damage of bacteria. Full article

(This article belongs to the Special Issue Materials for Infectious Diseases)

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16 pages, 4556 KiB

Open AccessArticle

Antibacterial and Cellular Behaviors of Novel Zinc-Doped Hydroxyapatite/Graphene Nanocomposite for Bone Tissue Engineering

by H. Maleki-Ghaleh, M. H. Siadati, A. Fallah, B. Koc, M. Kavanlouei, P. Khademi-Azandehi, E. Moradpur-Tari, Y. Omidi, J. Barar, Y. Beygi-Khosrowshahi, Alan P. Kumar and K. Adibkia

Int. J. Mol. Sci. 2021, 22(17), 9564; https://doi.org/10.3390/ijms22179564 - 03 Sep 2021

Cited by 42 | Viewed by 3569

Abstract

Bacteria are one of the significant causes of infection in the body after scaffold implantation. Effective use of nanotechnology to overcome this problem is an exciting and practical solution. Nanoparticles can cause bacterial degradation by the electrostatic interaction with receptors and cell walls. [...] Read more.

Bacteria are one of the significant causes of infection in the body after scaffold implantation. Effective use of nanotechnology to overcome this problem is an exciting and practical solution. Nanoparticles can cause bacterial degradation by the electrostatic interaction with receptors and cell walls. Simultaneously, the incorporation of antibacterial materials such as zinc and graphene in nanoparticles can further enhance bacterial degradation. In the present study, zinc-doped hydroxyapatite/graphene was synthesized and characterized as a nanocomposite material possessing both antibacterial and bioactive properties for bone tissue engineering. After synthesizing the zinc-doped hydroxyapatite nanoparticles using a mechanochemical process, they were composited with reduced graphene oxide. The nanoparticles and nanocomposite samples were extensively investigated by transmission electron microscopy, X-ray diffraction, and Raman spectroscopy. Their antibacterial behaviors against Escherichia coli and Staphylococcus aureus were studied. The antibacterial properties of hydroxyapatite nanoparticles were found to be improved more than 2.7 and 3.4 times after zinc doping and further compositing with graphene, respectively. In vitro cell assessment was investigated by a cell viability test and alkaline phosphatase activity using mesenchymal stem cells, and the results showed that hydroxyapatite nanoparticles in the culture medium, in addition to non-toxicity, led to enhanced proliferation of bone marrow stem cells. Furthermore, zinc doping in combination with graphene significantly increased alkaline phosphatase activity and proliferation of mesenchymal stem cells. The antibacterial activity along with cell biocompatibility/bioactivity of zinc-doped hydroxyapatite/graphene nanocomposite are the highly desirable and suitable biological properties for bone tissue engineering successfully achieved in this work. Full article

(This article belongs to the Special Issue Materials for Infectious Diseases)

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17 pages, 5305 KiB

Open AccessArticle

Bioactivity and Antibacterial Behaviors of Nanostructured Lithium-Doped Hydroxyapatite for Bone Scaffold Application

by Pardis Keikhosravani, Hossein Maleki-Ghaleh, Amir Kahaie Khosrowshahi, Mahdi Bodaghi, Ziba Dargahi, Majid Kavanlouei, Pooriya Khademi-Azandehi, Ali Fallah, Younes Beygi-Khosrowshahi and M. Hossein Siadati

Int. J. Mol. Sci. 2021, 22(17), 9214; https://doi.org/10.3390/ijms22179214 - 26 Aug 2021

Cited by 24 | Viewed by 3378

Abstract

The material for bone scaffold replacement should be biocompatible and antibacterial to prevent scaffold-associated infection. We biofunctionalized the hydroxyapatite (HA) properties by doping it with lithium (Li). The HA and 4 Li-doped HA (0.5, 1.0, 2.0, 4.0 wt.%) samples were investigated to find [...] Read more.

The material for bone scaffold replacement should be biocompatible and antibacterial to prevent scaffold-associated infection. We biofunctionalized the hydroxyapatite (HA) properties by doping it with lithium (Li). The HA and 4 Li-doped HA (0.5, 1.0, 2.0, 4.0 wt.%) samples were investigated to find the most suitable Li content for both aspects. The synthesized nanoparticles, by the mechanical alloying method, were cold-pressed uniaxially and then sintered for 2 h at 1250 °C. Characterization using field-emission scanning electron microscopy (FE-SEM) revealed particle sizes in the range of 60 to 120 nm. The XRD analysis proved the formation of HA and Li-doped HA nanoparticles with crystal sizes ranging from 59 to 89 nm. The bioactivity of samples was investigated in simulated body fluid (SBF), and the growth of apatite formed on surfaces was evaluated using SEM and EDS. Cellular behavior was estimated by MG63 osteoblast-like cells. The results of apatite growth and cell analysis showed that 1.0 wt.% Li doping was optimal to maximize the bioactivity of HA. Antibacterial characteristics against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were performed by colony-forming unit (CFU) tests. The results showed that Li in the structure of HA increases its antibacterial properties. HA biofunctionalized by Li doping can be considered a suitable option for the fabrication of bone scaffolds due to its antibacterial and unique bioactivity properties. Full article

(This article belongs to the Special Issue Materials for Infectious Diseases)

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11 pages, 1885 KiB

Open AccessArticle

Oxidative Inactivation of SARS-CoV-2 on Photoactive AgNPs@TiO₂ Ceramic Tiles

by Ridha Djellabi, Nicoletta Basilico, Serena Delbue, Sarah D’Alessandro, Silvia Parapini, Giuseppina Cerrato, Enzo Laurenti, Ermelinda Falletta and Claudia Letizia Bianchi

Int. J. Mol. Sci. 2021, 22(16), 8836; https://doi.org/10.3390/ijms22168836 - 17 Aug 2021

Cited by 20 | Viewed by 3182

Abstract

The current SARS-CoV-2 pandemic causes serious public health, social, and economic issues all over the globe. Surface transmission has been claimed as a possible SARS-CoV-2 infection route, especially in heavy contaminated environmental surfaces, including hospitals and crowded public places. Herein, we studied the [...] Read more.

The current SARS-CoV-2 pandemic causes serious public health, social, and economic issues all over the globe. Surface transmission has been claimed as a possible SARS-CoV-2 infection route, especially in heavy contaminated environmental surfaces, including hospitals and crowded public places. Herein, we studied the deactivation of SARS-CoV-2 on photoactive AgNPs@TiO₂ coated on industrial ceramic tiles under dark, UVA, and LED light irradiations. SARS-CoV-2 inactivation is effective under any light/dark conditions. The presence of AgNPs has an important key to limit the survival of SARS-CoV-2 in the dark; moreover, there is a synergistic action when TiO₂ is decorated with Ag to enhance the virus photocatalytic inactivation even under LED. The radical oxidation was confirmed as the the central mechanism behind SARS-CoV-2 damage/inactivation by ESR analysis under LED light. Therefore, photoactive AgNPs@TiO₂ ceramic tiles could be exploited to fight surface infections, especially during viral severe pandemics. Full article

(This article belongs to the Special Issue Materials for Infectious Diseases)

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Review

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16 pages, 759 KiB

Open AccessReview

Graphene Oxide (GO): A Promising Nanomaterial against Infectious Diseases Caused by Multidrug-Resistant Bacteria

by Ida M. J. Ng and Suhaili Shamsi

Int. J. Mol. Sci. 2022, 23(16), 9096; https://doi.org/10.3390/ijms23169096 - 13 Aug 2022

Cited by 16 | Viewed by 2387

Abstract

Infectious diseases are major threat due to it being the main cause of enormous morbidity and mortality in the world. Multidrug-resistant (MDR) bacteria put an additional burden of infection leading to inferior treatment by the antibiotics of the latest generations. The emergence and [...] Read more.

Infectious diseases are major threat due to it being the main cause of enormous morbidity and mortality in the world. Multidrug-resistant (MDR) bacteria put an additional burden of infection leading to inferior treatment by the antibiotics of the latest generations. The emergence and spread of MDR bacteria (so-called “superbugs”), due to mutations in the bacteria and overuse of antibiotics, should be considered a serious concern. Recently, the rapid advancement of nanoscience and nanotechnology has produced several antimicrobial nanoparticles. It has been suggested that nanoparticles rely on very different mechanisms of antibacterial activity when compared to antibiotics. Graphene-based nanomaterials are fast emerging as “two-dimensional wonder materials” due to their unique structure and excellent mechanical, optical and electrical properties and have been exploited in electronics and other fields. Emerging trends show that their exceptional properties can be exploited for biomedical applications, especially in drug delivery and tissue engineering. Moreover, graphene derivatives were found to have in vitro antibacterial properties. In the recent years, there have been many studies demonstrating the antibacterial effects of GO on various types of bacteria. In this review article, we will be focusing on the aforementioned studies, focusing on the mechanisms, difference between the studies, limitations and future directions. Full article

(This article belongs to the Special Issue Materials for Infectious Diseases)

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31 pages, 2990 KiB

Open AccessReview

Emerging Advances of Nanotechnology in Drug and Vaccine Delivery against Viral Associated Respiratory Infectious Diseases (VARID)

by Amir Seyfoori, Mahdieh Shokrollahi Barough, Pooneh Mokarram, Mazaher Ahmadi, Parvaneh Mehrbod, Alireza Sheidary, Tayyebeh Madrakian, Mohammad Kiumarsi, Tavia Walsh, Kielan D. McAlinden, Chandra C. Ghosh, Pawan Sharma, Amir A. Zeki, Saeid Ghavami and Mohsen Akbari

Int. J. Mol. Sci. 2021, 22(13), 6937; https://doi.org/10.3390/ijms22136937 - 28 Jun 2021

Cited by 19 | Viewed by 5992

Abstract

Viral-associated respiratory infectious diseases are one of the most prominent subsets of respiratory failures, known as viral respiratory infections (VRI). VRIs are proceeded by an infection caused by viruses infecting the respiratory system. For the past 100 years, viral associated respiratory epidemics have [...] Read more.

Viral-associated respiratory infectious diseases are one of the most prominent subsets of respiratory failures, known as viral respiratory infections (VRI). VRIs are proceeded by an infection caused by viruses infecting the respiratory system. For the past 100 years, viral associated respiratory epidemics have been the most common cause of infectious disease worldwide. Due to several drawbacks of the current anti-viral treatments, such as drug resistance generation and non-targeting of viral proteins, the development of novel nanotherapeutic or nano-vaccine strategies can be considered essential. Due to their specific physical and biological properties, nanoparticles hold promising opportunities for both anti-viral treatments and vaccines against viral infections. Besides the specific physiological properties of the respiratory system, there is a significant demand for utilizing nano-designs in the production of vaccines or antiviral agents for airway-localized administration. SARS-CoV-2, as an immediate example of respiratory viruses, is an enveloped, positive-sense, single-stranded RNA virus belonging to the coronaviridae family. COVID-19 can lead to acute respiratory distress syndrome, similarly to other members of the coronaviridae. Hence, reviewing the current and past emerging nanotechnology-based medications on similar respiratory viral diseases can identify pathways towards generating novel SARS-CoV-2 nanotherapeutics and/or nano-vaccines. Full article

(This article belongs to the Special Issue Materials for Infectious Diseases)

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28 pages, 3771 KiB

Open AccessReview

The Molecular Basis of COVID-19 Pathogenesis, Conventional and Nanomedicine Therapy

by Shirin Kouhpayeh, Laleh Shariati, Maryam Boshtam, Ilnaz Rahimmanesh, Mina Mirian, Yasaman Esmaeili, Malihe Najaflu, Negar Khanahmad, Mehrdad Zeinalian, Maria Trovato, Franklin R Tay, Hossein Khanahmad and Pooyan Makvandi

Int. J. Mol. Sci. 2021, 22(11), 5438; https://doi.org/10.3390/ijms22115438 - 21 May 2021

Cited by 23 | Viewed by 6531

Abstract

In late 2019, a new member of the Coronaviridae family, officially designated as “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2), emerged and spread rapidly. The Coronavirus Disease-19 (COVID-19) outbreak was accompanied by a high rate of morbidity and mortality worldwide and was declared [...] Read more.

In late 2019, a new member of the Coronaviridae family, officially designated as “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2), emerged and spread rapidly. The Coronavirus Disease-19 (COVID-19) outbreak was accompanied by a high rate of morbidity and mortality worldwide and was declared a pandemic by the World Health Organization in March 2020. Within the Coronaviridae family, SARS-CoV-2 is considered to be the third most highly pathogenic virus that infects humans, following the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV). Four major mechanisms are thought to be involved in COVID-19 pathogenesis, including the activation of the renin-angiotensin system (RAS) signaling pathway, oxidative stress and cell death, cytokine storm, and endothelial dysfunction. Following virus entry and RAS activation, acute respiratory distress syndrome develops with an oxidative/nitrosative burst. The DNA damage induced by oxidative stress activates poly ADP-ribose polymerase-1 (PARP-1), viral macrodomain of non-structural protein 3, poly (ADP-ribose) glycohydrolase (PARG), and transient receptor potential melastatin type 2 (TRPM2) channel in a sequential manner which results in cell apoptosis or necrosis. In this review, blockers of angiotensin II receptor and/or PARP, PARG, and TRPM2, including vitamin D3, trehalose, tannins, flufenamic and mefenamic acid, and losartan, have been investigated for inhibiting RAS activation and quenching oxidative burst. Moreover, the application of organic and inorganic nanoparticles, including liposomes, dendrimers, quantum dots, and iron oxides, as therapeutic agents for SARS-CoV-2 were fully reviewed. In the present review, the clinical manifestations of COVID-19 are explained by focusing on molecular mechanisms. Potential therapeutic targets, including the RAS signaling pathway, PARP, PARG, and TRPM2, are also discussed in depth. Full article

(This article belongs to the Special Issue Materials for Infectious Diseases)

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