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Carbohydr Polym ; 273: 118605, 2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1370153


Advanced biomaterials provide an interesting and versatile platform to implement new and more effective strategies to fight bacterial infections. Chitosan is one of these biopolymers and possesses relevant features for biomedical applications. Here we synthesized nanoparticles of chitosan derivatized with diethylaminoethyl groups (ChiDENPs) to emulate the choline residues in the pneumococcal cell wall and act as ligands for choline-binding proteins (CBPs). Firstly, we assessed the ability of diethylaminoethyl (DEAE) to sequester the CBPs present in the bacterial surface, thus promoting chain formation. Secondly, the CBP-binding ability of ChiDENPs was purposed to encapsulate a bio-active molecule, the antimicrobial enzyme Cpl-711 (ChiDENPs-711), with improved stability over non-derivatized chitosan. The enzyme-loaded system released more than 90% of the active enzybiotic in ≈ 2 h, above the usual in vivo half-life of this kind of enzymes. Therefore, ChiDENPs provide a promising platform for the controlled release of CBP-enzybiotics in biological contexts.

Anti-Bacterial Agents/pharmacology , Biomimetic Materials/chemistry , Chitosan/analogs & derivatives , Drug Carriers/chemistry , Endopeptidases/pharmacology , Nanoparticles/chemistry , A549 Cells , Anti-Bacterial Agents/chemistry , Bacterial Proteins/metabolism , Biomimetic Materials/metabolism , Chitosan/chemistry , Chitosan/metabolism , Drug Carriers/metabolism , Drug Liberation , Endopeptidases/chemistry , Humans , Nanoparticles/metabolism , Streptococcus pneumoniae/drug effects
J Virol ; 95(4)2021 01 28.
Article in English | MEDLINE | ID: covidwho-1054610


Among seven coronaviruses that infect humans, three (severe acute respiratory syndrome coronavirus [SARS-CoV], Middle East respiratory syndrome coronavirus [MERS-CoV], and the newly identified severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) are associated with a severe, life-threatening respiratory infection and multiorgan failure. We previously proposed that the cationically modified chitosan N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC) is a potent inhibitor of human coronavirus NL63 (HCoV-NL63). Next, we demonstrated the broad-spectrum antiviral activity of the compound, as it inhibited all low-pathogenicity human coronaviruses (HCoV-NL63, HCoV-229E, HCoV-OC43, and HCoV-HKU1). Here, using in vitro and ex vivo models of human airway epithelia, we show that HTCC effectively blocks MERS-CoV and SARS-CoV-2 infection. We also confirmed the mechanism of action for these two viruses, showing that the polymer blocks the virus entry into the host cell by interaction with the S protein.IMPORTANCE The beginning of 2020 brought us information about the novel coronavirus emerging in China. Rapid research resulted in the characterization of the pathogen, which appeared to be a member of the SARS-like cluster, commonly seen in bats. Despite the global and local efforts, the virus escaped the health care measures and rapidly spread in China and later globally, officially causing a pandemic and global crisis in March 2020. At present, different scenarios are being written to contain the virus, but the development of novel anticoronavirals for all highly pathogenic coronaviruses remains the major challenge. Here, we describe the antiviral activity of an HTCC compound, previously developed by us, which may be used as a potential inhibitor of currently circulating highly pathogenic coronaviruses-SARS-CoV-2 and MERS-CoV.

COVID-19/drug therapy , Chitosan/analogs & derivatives , Coronavirus Infections/drug therapy , Middle East Respiratory Syndrome Coronavirus/drug effects , Quaternary Ammonium Compounds/pharmacology , SARS-CoV-2/drug effects , Antiviral Agents/pharmacology , COVID-19/epidemiology , COVID-19/virology , Chitosan/pharmacology , Coronavirus Infections/metabolism , Coronavirus Infections/virology , Humans , Middle East Respiratory Syndrome Coronavirus/metabolism , Middle East Respiratory Syndrome Coronavirus/physiology , Pandemics , Respiratory Mucosa/drug effects , Respiratory Mucosa/virology , SARS-CoV-2/metabolism , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization/drug effects
Carbohydr Polym ; 250: 116800, 2020 Dec 15.
Article in English | MEDLINE | ID: covidwho-718667


Chitosan, as a biodegradable and biocompatible polymer, is characterized by anti-microbial and anti-cancer properties. It lately has received a widespread interest for use as the pulmonary particulate backbone materials of drug carrier for the treatment of infectious disease and cancer. The success of chitosan as pulmonary particulate drug carrier is a critical interplay of their mucoadhesive, permeation enhancement and site/cell-specific attributes. In the case of nanocarriers, various microencapsulation and micro-nano blending systems have been devised to equip them with an appropriate aerodynamic character to enable efficient pulmonary aerosolization and inhalation. The late COVID-19 infection is met with acute respiratory distress syndrome and cancer. Chitosan and its derivatives are found useful in combating HCoV and cancer as a function of their molecular weight, substituent type and its degree of substitution. The interest in chitosan is expected to rise in the next decade from the perspectives of drug delivery in combination with its therapeutic performance.

Anti-Infective Agents/chemistry , Antineoplastic Agents/chemistry , Chitosan/analogs & derivatives , Drug Carriers/chemistry , Anti-Infective Agents/pharmacology , Anti-Infective Agents/therapeutic use , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Betacoronavirus/isolation & purification , Biocompatible Materials/chemistry , COVID-19 , Cell Survival/drug effects , Coronavirus Infections/drug therapy , Coronavirus Infections/pathology , Coronavirus Infections/virology , Humans , Lung Neoplasms/pathology , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , SARS-CoV-2