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Int J Mol Sci ; 22(24)2021 Dec 18.
Article in English | MEDLINE | ID: covidwho-1580689


Global reports on multidrug resistance (MDR) and life-threatening pathogens such as SARS-CoV-2 and Candida cruris have stimulated researchers to explore new antimicrobials that are eco-friendly and economically viable. In this context, biodegradable polymers such as nisin, chitin, and pullulan play an important role in solving the problem. Pullulan is an important edible, biocompatible, water-soluble polymer secreted by Aureobasidium pullulans that occurs ubiquitously. It consists of maltotriose units linked with α-1,6 glycosidic bonds and is classed as Generally Regarded as Safe (GRAS) by the Food and Drug Administration (FDA) in the USA. Pullulan is known for its antibacterial, antifungal, antiviral, and antitumor activities when incorporated with other additives such as antibiotics, drugs, nanoparticles, and so on. Considering the importance of its antimicrobial activities, this polymer can be used as a potential antimicrobial agent against various pathogenic microorganisms including the multidrug-resistant (MDR) pathogens. Moreover, pullulan has ability to synthesize biogenic silver nanoparticles (AgNPs), which are remarkably efficacious against pathogenic microbes. The pullulan-based nanocomposites can be applied for wound healing, food packaging, and also enhancing the shelf-life of fruits and vegetables. In this review, we have discussed biosynthesis of pullulan and its role as antibacterial, antiviral, and antifungal agent. Pullulan-based films impregnated with different antimicrobials such as AgNPs, chitosan, essential oils, and so on, forming nanocomposites have also been discussed as natural alternatives to combat the problems posed by pathogens.

Anti-Infective Agents/pharmacology , Drug Resistance, Multiple/drug effects , Glucans/biosynthesis , Anti-Bacterial Agents , Anti-Infective Agents/chemistry , Antifungal Agents , COVID-19 , Chitin/pharmacology , Chitosan/chemistry , Drug Resistance, Multiple/physiology , Food Packaging , Glucans/metabolism , Glucans/pharmacology , Humans , Metal Nanoparticles/chemistry , Nanocomposites/chemistry , Nisin/pharmacology , Polymers/chemistry , SARS-CoV-2
Int J Mol Sci ; 22(5)2021 Mar 04.
Article in English | MEDLINE | ID: covidwho-1129732


BACKGROUND: Acute lung injury (ALI) or its most advanced form, acute respiratory distress syndrome (ARDS) is a severe inflammatory pulmonary process triggered by a variety of insults including sepsis, viral or bacterial pneumonia, and mechanical ventilator-induced trauma. Currently, there are no effective therapies available for ARDS. We have recently reported that a novel small molecule AVR-25 derived from chitin molecule (a long-chain polymer of N-acetylglucosamine) showed anti-inflammatory effects in the lungs. The goal of this study was to determine the efficacy of two chitin-derived compounds, AVR-25 and AVR-48, in multiple mouse models of ALI/ARDS. We further determined the safety and pharmacokinetic (PK) profile of the lead compound AVR-48 in rats. METHODS: ALI in mice was induced by intratracheal instillation of a single dose of lipopolysaccharide (LPS; 100 µg) for 24 h or exposed to hyperoxia (100% oxygen) for 48 h or undergoing cecal ligation and puncture (CLP) procedure and observation for 10 days. RESULTS: Both chitin derivatives, AVR-25 and AVR-48, showed decreased neutrophil recruitment and reduced inflammation in the lungs of ALI mice. Further, AVR-25 and AVR-48 mediated diminished lung inflammation was associated with reduced expression of lung adhesion molecules with improvement in pulmonary endothelial barrier function, pulmonary edema, and lung injury. Consistent with these results, CLP-induced sepsis mice treated with AVR-48 showed a significant increase in survival of the mice (80%) and improved lung histopathology in the treated CLP group. AVR-48, the lead chitin derivative compound, demonstrated a good safety profile. CONCLUSION: Both AVR-25 and AVR-48 demonstrate the potential to be developed as therapeutic agents to treat ALI/ARDS.

Acute Lung Injury/drug therapy , Immunologic Factors/pharmacology , Respiratory Distress Syndrome/drug therapy , Small Molecule Libraries/pharmacology , Animals , Chitin/pharmacology , Disease Models, Animal , Female , Lipopolysaccharides/pharmacology , Lung/drug effects , Male , Mice , Mice, Inbred C57BL , Pneumonia/drug therapy , Pulmonary Edema/drug therapy , Rats , Rats, Sprague-Dawley , Sepsis/drug therapy
Int J Biol Macromol ; 179: 33-44, 2021 May 15.
Article in English | MEDLINE | ID: covidwho-1085549


Chitosan is a deacetylated polycationic polysaccharide derived from chitin. It is structurally constituted of N-acetyl-D-glucosamine and ß-(1-4)-linked D-glucosamine where acetyl groups are randomly distributed across the polymer. The parameters of deacetylation and depolymerization process greatly influence various physico-chemical properties of chitosan and thus, offer a great degree of manipulation to synthesize chitosan of interest for various industrial and biomedical applications. Chitosan and its various derivatives have been a potential molecule of investigation in the area of anti-microbials especially anti-fungal, anti-bacterial and antiviral. The current review predominantly highlights and discusses about the antiviral activities of chitosan and its various substituted derivatives against a wide spectrum of human, animal, plants and bacteriophage viruses. The extrinsic and intrinsic factors that affect antiviral efficacy of chitosan have also been talked about. With the rapid unfolding of COVID-19 pandemic across the globe, we look for chitosan as a plausible potent antiviral molecule for fighting this disease. Through this review, we present enough literature data supporting role of chitosan against different strains of SARS viruses and also chitosan targeting CD147 receptors, a novel route for invasion of SARS-CoV-2 into host cells. We speculate the possibility of using chitosan as potential molecule against SARS-CoV-2 virus.

COVID-19/drug therapy , Chitosan/pharmacology , SARS-CoV-2/drug effects , Animals , Antiviral Agents/pharmacology , COVID-19/virology , Chitin/chemistry , Chitin/pharmacology , Chitosan/chemistry , Humans , Pandemics/prevention & control