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1.
Microbiol Spectr ; 11(3): e0084423, 2023 Jun 15.
Article in English | MEDLINE | ID: covidwho-2319398

ABSTRACT

The biological activity of polycations is usually associated with their biocidal properties. Their antibacterial features are well known, but in this work, observations on the antifungal properties of macromolecules obtained by methacrylamido propyl trimethyl ammonium chloride (MAPTAC) polymerization are presented. The results, not previously reported, make it possible to correlate antifungal properties directly with the structure of the macromolecule, in particular the molecular mass. The polymers described here have antifungal activity against some filamentous fungi. The strongest effect occurs for polymers with a mass of about 0.5 mDa which have confirmed activity against the multidrug-resistant species Scopulariopsis brevicaulis, Fusarium oxysporum, and Fusarium solani, as well as the dermatophytes Trichophyton mentagrophytes, Trichophyton rubrum, Trichophyton interdigitale, and Trichophyton tonsurans. In addition, this publication describes the effects of these macromolecular systems on serum and blood components and provides a preliminary assessment of toxicity on cell lines of skin-forming cells, i.e., fibroblasts and keratinocytes. Additionally, using a Franz diffusion chamber, a negligibly low transport of the active polymer through the skin was demonstrated, which is a desirable effect for externally applied antifungal drugs. IMPORTANCE Infectious diseases are a very big medical, social, and economic problem. Even before the COVID-19 pandemic, certain infections were among of the most common causes of death. The difficulties in the treatment of infectious diseases concern in particular fungal diseases, against which we have only a few classes of drugs represented by a few substances. The publication presents the preliminary results of the in vitro antifungal activity studies of four MAPTAC polymers on different fungal species and their cytotoxicity to human cells (fibroblasts and keratinocytes). The paper also compares these properties with analogous ones of two commonly used antifungal drugs, ciclopirox and terbinafine.


Subject(s)
Antifungal Agents , COVID-19 , Humans , Antifungal Agents/toxicity , Ammonium Chloride , Pandemics , Microbial Sensitivity Tests , Polymers/pharmacology
2.
Angew Chem Int Ed Engl ; 62(29): e202304010, 2023 07 17.
Article in English | MEDLINE | ID: covidwho-2312956

ABSTRACT

Mucins are the key component of the defensive mucus barrier. They are extended fibers of very high molecular weight with diverse biological functions depending strongly on their specific structural parameters. Here, we present a mucin-inspired nanostructure, produced via a synthetic methodology to prepare methacrylate-based dendronized polysulfates (MIP-1) on a multi gram-scale with high molecular weight (MW=450 kDa) and thiol end-functionalized mucin-inspired polymer (MIP) via RAFT polymerization. Cryo-electron tomography (Cryo-ET) analysis of MIP-1 confirmed a mucin-mimetic wormlike single-chain fiber structure (length=144±59 nm) in aqueous solution. This biocompatible fiber showed promising activity against SARS-CoV-2 and its mutant strain, with a remarkable low half maximal (IC50 ) inhibitory concentration (IC50 =10.0 nM). Additionally, we investigate the impact of fiber length on SARS-CoV-2 inhibition by testing other functional polymers (MIPs) of varying fiber lengths.


Subject(s)
COVID-19 , Molecular Imprinting , Humans , Mucins , SARS-CoV-2 , Polymers/pharmacology , Polymers/chemistry , Molecular Imprinting/methods
3.
J Control Release ; 347: 561-589, 2022 07.
Article in English | MEDLINE | ID: covidwho-2249019

ABSTRACT

Dissolvable transdermal microneedles (µND) are promising micro-devices used to transport a wide selection of active compounds into the skin. To provide an effective therapeutic outcome, µNDs must pierce the human stratum corneum (~10 to 20 µm), without rupturing or bending during penetration, then release their cargo at the predetermined area and time. The ability of dissolvable µND arrays/patches to sufficiently pierce the skin is a crucial requirement, which depends on the material composition, µND geometry and fabrication techniques. This comprehensive review not only provides contemporary knowledge on the µND design approaches, but also the materials science facilitating these delivery systems and the opportunities these advanced materials can provide to enhance clinical outcomes.


Subject(s)
Needles , Polymers , Administration, Cutaneous , Drug Delivery Systems/methods , Humans , Microinjections/methods , Polymers/pharmacology , Skin
4.
Langmuir ; 39(15): 5408-5417, 2023 04 18.
Article in English | MEDLINE | ID: covidwho-2265219

ABSTRACT

We demonstrate that cholesterol-modified polyethylene glycol has antiviral activity, exerted by anchoring to plasma membranes and sterically inhibiting viruses from entering cells. These polymers distribute sparsely on cell membranes even at binding saturation. However, the polymers have sufficient elastic repulsion energy to repel various kinds of viruses with sizes larger than the mean distances between anchored polymers, including SARS-CoV-2 pseudoparticles. Our strategy can be applied to protect the epithelium from viruses. When these polymers are applied to the epithelium, they localize on the apical surface due to the tight junction barriers, resulting in surface-only coating. Therefore, these polymers can prevent the entry of viruses into cells of the epithelium with minimal disturbance to lateral cell-cell interactions and organizations.


Subject(s)
COVID-19 , Polymers , Humans , Polymers/pharmacology , Antiviral Agents/pharmacology , SARS-CoV-2 , Cell Membrane
5.
ACS Biomater Sci Eng ; 9(1): 329-339, 2023 01 09.
Article in English | MEDLINE | ID: covidwho-2160144

ABSTRACT

Bacteria and viruses can adhere onto diverse surfaces and be transmitted in multiple ways. A bifunctional coating that integrates both antibacterial and antiviral activities is a promising approach to mitigate bacterial and viral infections arising from a contaminated surface. However, current coating approaches encounter a slow reaction, limited activity against diverse bacteria or viruses, short-term activity, difficulty in scaling-up, and poor adaptation to diverse material surfaces. Here, we report a new one-step strategy for the development of a polydopamine-based nonfouling antibacterial and antiviral coating by the codeposition of various components. The in situ formed nanosilver in the presence of polydopamine was incorporated into the coating and served as both antibacterial and antiviral agents. In addition, the coassembly of polydopamine and a nonfouling hydrophilic polymer was constructed to prevent the adhesion of bacteria and viruses on the coating. The coating was prepared on model surfaces and thoroughly characterized using various surface analytical techniques. The coating exhibited strong antifouling properties with a reduction of nonspecific protein adsorption up to 90%. The coating was tested against both Gram-positive and Gram-negative bacteria and showed long-term antibacterial effectiveness, which correlated with the composition of the coating. The antiviral activity of the coating was evaluated against human coronavirus 229E. A possible mechanism of action of the coating was proposed. We anticipate that the optimized coating will have applications in the development of infection prevention devices and surfaces.


Subject(s)
Biofouling , Dopamine , Humans , Dopamine/pharmacology , Biofouling/prevention & control , Anti-Bacterial Agents/pharmacology , Antiviral Agents/pharmacology , Bacterial Adhesion , Coated Materials, Biocompatible/pharmacology , Gram-Negative Bacteria , Gram-Positive Bacteria , Polymers/pharmacology , Bacteria
6.
J Mater Chem B ; 10(45): 9349-9368, 2022 Nov 23.
Article in English | MEDLINE | ID: covidwho-2117996

ABSTRACT

Undesirable adhesion of microbes such as bacteria, fungi and viruses onto surfaces affects many industries such as marine, food, textile, and healthcare. In particular in healthcare and food packaging, the effects of unwanted microbial contamination can be life-threatening. With the current global COVID-19 pandemic, interest in the development of surfaces with superior anti-viral and anti-bacterial activities has multiplied. Polymers carrying anti-microbial properties are extensively used to functionalize material surfaces to inactivate infection-causing and biocide-resistant microbes including COVID-19. This review aims to introduce the fabrication of polymer-based antimicrobial surfaces through physical and chemical modifications, followed by the discussion of the inactivation mechanisms of conventional biocidal agents and new-generation antimicrobial macromolecules in polymer-modified antimicrobial surfaces. The advanced applications of polymer-based antimicrobial surfaces on personal protective equipment against COVID-19, food packaging materials, biomedical devices, marine vessels and textiles are also summarized to express the research trend in academia and industry.


Subject(s)
Anti-Infective Agents , COVID-19 Drug Treatment , Humans , Polymers/pharmacology , Polymers/chemistry , Pandemics , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Bacteria
7.
Microbiol Spectr ; 10(5): e0055022, 2022 Oct 26.
Article in English | MEDLINE | ID: covidwho-2068501

ABSTRACT

Iodine-containing systems show broad antiseptic properties that can be an invaluable tool in controlling infections in humans and animals. Here, we describe the first proof-of-concept studies on biocidal active polyamide- and polyurethane-iodine complexes that are produced in situ directly during the fabrication and/or polymerization process at laboratory and commercially relevant scales. These polymer-iodine materials are active against a broad range of microorganisms, including bacteria and fungi. It is suggested that the ease of manufacture and subsequent commercialization make said systems especially suited for applications as base materials for medical devices to reduce infection risks and control the spread of pathogens. IMPORTANCE Infectious diseases are of mounting medical and public concern. A major contributor to this trend is the proliferation of medical implants, which are inherently vulnerable to microbial contamination and the subsequent onset of hospital-acquired infections. Moreover, implant-associated infections in humans are often difficult to diagnose and treat and are associated with substantial health care costs. Here, we present the development of biocidal active polyamide- and polyurethane-iodine complexes that are generated in situ during fabrication. We show that the excellent antiseptic properties of water-soluble povidone-iodine can be similarly realized in water-insoluble engineering plastics, specifically polyamide- and polyurethane-iodine. These complexes have inherent biocidal activity against major pathogenic bacteria and fungi.


Subject(s)
Anti-Infective Agents, Local , Iodine , Animals , Humans , Povidone-Iodine , Iodine/pharmacology , Polymers/pharmacology , Polyurethanes , Nylons , Bacteria , Water
8.
Lett Appl Microbiol ; 75(5): 1346-1353, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-1992872

ABSTRACT

We previously reported a novel polymeric surface coating, namely, HaloFilm™ that can immobilize and extend the antimicrobial activity of chlorine on surfaces. In this study, we demonstrated the continuous antiviral efficacy of HaloFilm when applied on stainless steel and cotton gauze as two representative models for non-porous and porous surfaces against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Forty-eight hours post HaloFilm application and chlorination and 2 h post the viral challenge, the inoculum titre was reduced by 2.25 ± 0.33 and ≥4.36 ± 0.23 log10 TCID50 on non-porous and porous surfaces, respectively. The half-life of the virus was shorter (13.86 min) on a HaloFilm-coated surface than what has been reported on copper (46.44 min).


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Antiviral Agents/pharmacology , Chlorine/pharmacology , Polymers/pharmacology , Stainless Steel , Copper
9.
Biomater Sci ; 10(8): 1904-1919, 2022 Apr 12.
Article in English | MEDLINE | ID: covidwho-1747168

ABSTRACT

The outbreak of the Covid-19 pandemic due to the SARS-CoV-2 coronavirus has accelerated the search for innovative antivirals with possibly broad-spectrum efficacy. One of the possible strategies is to inhibit the replication of the virus by preventing or limiting its entry into the cells. Nanomaterials derived from lysine, an essential amino acid capable of forming homopeptides of different shapes and sizes through thermal polymerization, are an exciting antiviral option. In this review, we have critically compared the antiviral activities and mechanisms of action of lysine and its possible analogues in the form of linear, hyperbranched, dendrimer and nanoparticle polymers. The polycationic nature, as well as the structure of polylysine in its various forms, favours the electrostatic interaction with viruses by inhibiting their replication and endocytosis. In the case of lysine alone, the antiviral action is instead carried out inside the cell. The experimental results obtained so far show that the development of antivirals based on amino acids that inhibit the entry of viruses into cells represents a definite possibility for developing challenging solutions against present and future pandemics.


Subject(s)
COVID-19 Drug Treatment , Nanostructures , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Humans , Lysine , Pandemics , Polymers/pharmacology , SARS-CoV-2
10.
Adv Mater ; 34(18): e2109580, 2022 May.
Article in English | MEDLINE | ID: covidwho-1712016

ABSTRACT

Lipid-membrane-targeting strategies hold great promise to develop broad-spectrum antivirals. However, it remains a big challenge to identify novel membrane-based targets of viruses and virus-infected cells for development of precision targeted approaches. Here, it is discovered that viroporins, viral-encoded ion channels, which have been reported to mediate release of hydrogen ions, trigger membrane acidification of virus-infected cells. Through development of a fine-scale library of gradient pH-sensitive (GPS) polymeric nanoprobes, the cellular membrane pH transitions are measured from pH 6.8-7.1 (uninfection) to pH 6.5-6.8 (virus-infection). In response to the subtle pH alterations, the GPS polymer with sharp response at pH 6.8 (GPS6.8 ) selectively binds to virus-infected cell membranes or the viral envelope, and even completely disrupts the viral envelope. Accordingly, GPS6.8 treatment exerts suppressive effects on a wide variety of viruses including SARS-CoV-2 through triggering viral-envelope lysis rather than affecting immune pathway or viability of host cells. Murine viral-infection models exhibit that supplementation of GPS6.8 decreases viral titers and ameliorates inflammatory damage. Thus, the gradient pH-sensitive nanotechnology offers a promising strategy for accurate detection of biological pH environments and robust interference with viruses.


Subject(s)
COVID-19 , Viruses , Animals , Antiviral Agents/pharmacology , Hydrogen-Ion Concentration , Mice , Polymers/pharmacology , SARS-CoV-2 , Viroporin Proteins , Viruses/metabolism
11.
Bioorg Chem ; 119: 105550, 2022 02.
Article in English | MEDLINE | ID: covidwho-1561636

ABSTRACT

Infectious diseases caused by new or unknown bacteria and viruses, such as anthrax, cholera, tuberculosis and even COVID-19, are a major threat to humanity. Thus, the development of new synthetic compounds with efficient antimicrobial activity is a necessity. Herein, rationally designed novel multifunctional cationic alternating copolymers were directly synthesized through a step-growth polymerization reaction using a bivalent electrophilic cross-linker containing disulfide bonds and a diamine heterocyclic ring. To optimize the activity of these alternating copolymers, several different diamines and cross-linkers were explored to find the highest antibacterial effects. The synthesized nanopolymers not only displayed good to excellent antibacterial activity as judged by minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and Escherichia coli, but also reduced the number of biofilm cells even at low concentrations, without killing mammalian cells. Furthermore, in vivo experiments using infected burn wounds in mice demonstrated good antibacterial activity and stimulated wound healing, without causing systemic inflammation. These findings suggest that the multifunctional cationic nanopolymers have potential as a novel antibacterial agent for eradication of multidrug resistant bacterial infections.


Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Biofilms/drug effects , Cations/pharmacology , Polymers/pharmacology , Wound Healing/drug effects , Amines/chemistry , Animals , Bacteria/drug effects , Bacterial Infections/drug therapy , Bacterial Infections/etiology , Burns/complications , COVID-19 , Cell Survival/drug effects , Cross-Linking Reagents , Drug Resistance, Multiple, Bacterial/drug effects , HEK293 Cells/drug effects , Humans , Mice , Microbial Sensitivity Tests , Polymers/chemistry
12.
J Am Chem Soc ; 143(49): 20529-20545, 2021 12 15.
Article in English | MEDLINE | ID: covidwho-1541126

ABSTRACT

Unquestionably, polymers have influenced the world over the past 100 years. They are now more crucial than ever since the COVID-19 pandemic outbreak. The pandemic paved the way for certain polymers to be in the spotlight, namely sequence-defined polymers such as messenger ribonucleic acid (mRNA), which was the first type of vaccine to be authorized in the U.S. and Europe to protect against the SARS-CoV-2 virus. This rise of mRNA will probably influence scientific research concerning nucleic acids in general and RNA therapeutics in specific. In this Perspective, we highlight the recent trends in sequence-controlled and sequence-defined polymers. Then we discuss mRNA vaccines as an example to illustrate the need of ultimate sequence control to achieve complex functions such as specific activation of the immune system. We briefly present how mRNA vaccines are produced, the importance of modified nucleotides, the characteristic features, and the advantages and challenges associated with this class of vaccines. Finally, we discuss the chances and opportunities for polymer chemistry to provide solutions and contribute to the future progress of RNA-based therapeutics. We highlight two particular roles of polymers in this context. One represents conjugation of polymers to nucleic acids to form biohybrids. The other is concerned with advanced polymer-based carrier systems for nucleic acids. We believe that polymers can help to address present problems of RNA-based therapeutic technologies and impact the field beyond the COVID-19 pandemic.


Subject(s)
Antiviral Agents/pharmacology , COVID-19 Drug Treatment , COVID-19 Vaccines/chemistry , Polymers/pharmacology , SARS-CoV-2/drug effects , mRNA Vaccines/chemistry , Animals , Drug Carriers , Humans
13.
Adv Healthc Mater ; 11(9): e2101898, 2022 05.
Article in English | MEDLINE | ID: covidwho-1482095

ABSTRACT

Disinfection using effective antimicrobials is essential in preventing the spread of infectious diseases. This COVID-19 pandemic has brought the need for effective disinfectants to greater attention due to the fast transmission of SARS-CoV-2. Current active ingredients in disinfectants are small molecules that microorganisms can develop resistance against after repeated long-term use and may penetrate the skin, causing harmful side-effects. To this end, a series of membrane-disrupting polyionenes that contain quaternary ammoniums and varying hydrophobic components is synthesized. They are effective against bacteria and fungi. They are also fast acting against clinically isolated drug resistant strains of bacteria. Formulating them with thickeners and nonionic surfactants do not affect their killing efficiency. These polyionenes are also effective in preventing infections caused by nonenveloped and enveloped viruses. Their effectiveness against mouse coronavirus (i.e., mouse hepatitis virus-MHV) depends on their hydrophobicity. The polyionenes with optimal compositions inactivates MHV completely in 30 s. More importantly, the polyionenes are effective in inhibiting SARS-CoV-2 by >99.999% within 30 s. While they are effective against the microorganisms, they do not cause damage to the skin and have a high oral lethal dose. Overall, these polyionenes are promising active ingredients for disinfection and prevention of viral and microbial infections.


Subject(s)
Anti-Infective Agents , COVID-19 , Disinfectants , Animals , Anti-Bacterial Agents , Anti-Infective Agents/pharmacology , Antiviral Agents/pharmacology , Bacteria , COVID-19/prevention & control , Disinfectants/pharmacology , Humans , Mice , Pandemics/prevention & control , Polymers/pharmacology , SARS-CoV-2
14.
Bioorg Chem ; 116: 105309, 2021 11.
Article in English | MEDLINE | ID: covidwho-1372894

ABSTRACT

Six new polyketone metabolites, compounds (1-6) and seven known polyketone compounds (7-13) were isolated from Rhodiola tibetica endophytic fungus Alternaria sp. The structural elucidation of five new polyketone metabolites were elucidated on the basis of spectroscopic including 2D NMR and HRMS and spectrometric analysis. Inhibition rate evaluation revealed that compounds 1(EC50 = 0.02 mM), 3(EC50 = 0.3 mM), 6(EC50 = 0.07 mM), 8(EC50 = 0.1 mM) and 9(EC50 = 0.04 mM) had inhibitory effect on the SARS-CoV-2 virus.


Subject(s)
Alternaria/chemistry , Antiviral Agents/isolation & purification , Antiviral Agents/pharmacology , Ketones/isolation & purification , Ketones/pharmacology , Polymers/isolation & purification , Polymers/pharmacology , SARS-CoV-2/drug effects , Antiviral Agents/chemistry , Humans , Ketones/chemistry , Molecular Structure , Polymers/chemistry
15.
Antiviral Res ; 194: 105162, 2021 10.
Article in English | MEDLINE | ID: covidwho-1347485

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has infected over 200 million people throughout the world as of August 2021. There are currently no approved treatments providing high chance of recovery from a severe case of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, and the beneficial effect of Remdesivir and passive immunization therapies may only be seen when administered early on disease onset. The emergence of variants is also raising concerns regarding the efficacy of antibody therapies, antivirals, and vaccines. Therefore, there is still a need to develop new antivirals. Here, we investigated the suitability of primary human epithelial cells from the trachea/bronchia (NHBE) and small airway (SAEC) as lung models of SARS-CoV-2 infection to determine, whether the microbicide polyphenylene carboxymethylene (PPCM) has antiviral activity against SARS-CoV-2. Both NHBE and SAEC expressed proteins required for virus entry in lung epithelial cells. However, these cells were only low to moderately permissive to SARS-CoV-2 as titers increased at best by 2.5 log10 during an 8-day kinetic. Levels of replication in SAEC, unlike in NHBE, were consistent with data from other studies using human normal tissues or air-liquid interface cultures, suggesting that SAEC may be more relevant to use than NHBE for drug screening. PPCM EC50 against SARS-CoV-2 was between 32 and 132 µg/ml with a selectivity index between 12 and 41, depending on the cell type and the infective dose used. PPCM doses were consistent with those previously showing effect against other human viruses. Finally, PPCM antiviral effect observed in SAEC was in line with reduction of inflammatory markers observed overly expressed in severe COVID-19 patients. Altogether, our data support the fact that PPCM should be further evaluated in vivo for toxicity and antiviral activity against SARS-CoV-2.


Subject(s)
Antiviral Agents/pharmacology , Epithelial Cells/virology , Polymers/pharmacology , SARS-CoV-2/drug effects , Antiviral Agents/chemistry , COVID-19/prevention & control , COVID-19/transmission , Epithelial Cells/drug effects , Humans , Lung/cytology , Lung/virology , Polymers/chemistry , Proof of Concept Study , SARS-CoV-2/genetics , Virus Internalization/drug effects , Virus Replication/drug effects
16.
J Biol Chem ; 297(2): 100940, 2021 08.
Article in English | MEDLINE | ID: covidwho-1293905

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 envelope protein (S2-E) is a conserved membrane protein that is important for coronavirus (CoV) assembly and budding. Here, we describe the recombinant expression and purification of S2-E in amphipol-class amphipathic polymer solutions, which solubilize and stabilize membrane proteins, but do not disrupt membranes. We found that amphipol delivery of S2-E to preformed planar bilayers results in spontaneous membrane integration and formation of viroporin cation channels. Amphipol delivery of the S2-E protein to human cells results in plasma membrane integration, followed by retrograde trafficking to the trans-Golgi network and accumulation in swollen perinuclear lysosomal-associated membrane protein 1-positive vesicles, likely lysosomes. CoV envelope proteins have previously been proposed to manipulate the luminal pH of the trans-Golgi network, which serves as an accumulation station for progeny CoV particles prior to cellular egress via lysosomes. Delivery of S2-E to cells will enable chemical biological approaches for future studies of severe acute respiratory syndrome coronavirus 2 pathogenesis and possibly even development of "Trojan horse" antiviral therapies. Finally, this work also establishes a paradigm for amphipol-mediated delivery of membrane proteins to cells.


Subject(s)
Cell Membrane/drug effects , Coronavirus Envelope Proteins/metabolism , Polymers/pharmacology , Propylamines/pharmacology , Surface-Active Agents/pharmacology , trans-Golgi Network/metabolism , Cell Membrane/metabolism , Coronavirus Envelope Proteins/genetics , HeLa Cells , Humans , Lipid Bilayers/chemistry , Lipid Bilayers/metabolism , Lysosomes/metabolism , Polymers/chemistry , Propylamines/chemistry , Protein Transport , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Surface-Active Agents/chemistry
17.
Adv Mater ; 33(26): e2008304, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1248674

ABSTRACT

Airborne pathogens pose high risks in terms of both contraction and transmission within the respiratory pathways, particularly the nasal region. However, there is little in the way of adequate intervention that can protect an individual or prevent further spread. This study reports on a nasal formulation with the capacity to combat such challenges, focusing on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Formulation of a polysaccharide-based spray, known for its mucoadhesive properties, is undertaken and it is characterized for its mechanical, spray distribution, and antiviral properties. The ability to engineer key mechanical characteristics such as dynamic yield stresses and high coverage is shown, through systematic understanding of the composite mixture containing both gellan and λ-carrageenan. Furthermore, the spray systems demonstrate highly potent capacities to prevent SARS-CoV-2 infection in Vero cells, resulting in complete inhibition when either treating, the cells, or the virus, prior to challenging for infection. From this data, a mechanism for both prophylaxis and prevention is proposed; where entrapment within a polymeric coating sterically blocks virus uptake into the cells, inactivating the virus, and allowing clearance within the viscous medium. As such, a fully preventative spray is formulated, targeted at protecting the lining of the upper respiratory pathways against SARS-CoV-2.


Subject(s)
Drug Compounding , Nasal Sprays , Polymers/chemistry , SARS-CoV-2/physiology , Animals , COVID-19/pathology , COVID-19/virology , Carrageenan/chemistry , Chlorocebus aethiops , Humans , Polymers/pharmacology , Polysaccharides, Bacterial/chemistry , SARS-CoV-2/isolation & purification , Vero Cells , Virus Internalization/drug effects
18.
Adv Healthc Mater ; 10(6): e2001433, 2021 03.
Article in English | MEDLINE | ID: covidwho-1046877

ABSTRACT

The ongoing pandemic of the coronavirus disease (Covid-19), caused by the spread of the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), highlights the need for broad-spectrum antiviral drugs. In this Essay, it is argued that such agents already exist and are readily available while highlighting the challenges that remain to translate them into the clinic. Multivalent inhibitors of viral infectivity based on polymers or supramolecular agents and nanoparticles are shown to be broadly acting against diverse pathogens in vitro as well as in vivo. Furthermore, uniquely, such agents can be virucidal. Polymers and nanoparticles are stable, do not require cold chain of transportation and storage, and can be obtained on large scale. Specifically, for the treatment of respiratory viruses and pulmonary diseases, these agents can be administered via inhalation/nebulization, as is currently investigated in clinical trials as a treatment against SARS CoV-2/Covid-19. It is believed that with due optimization and clinical validation, multivalent inhibitors of viral infectivity can claim their rightful position as broad-spectrum antiviral agents.


Subject(s)
Antiviral Agents/therapeutic use , Virus Diseases/drug therapy , Antibodies, Neutralizing/therapeutic use , Antiviral Agents/pharmacology , COVID-19/pathology , COVID-19/virology , Humans , Nanoparticles/chemistry , Nanoparticles/toxicity , Polymers/chemistry , Polymers/pharmacology , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification , Virus Internalization/drug effects , COVID-19 Drug Treatment
19.
Polim Med ; 50(2): 79-82, 2020.
Article in English | MEDLINE | ID: covidwho-1044932

ABSTRACT

Viruses that are pathogenic to humans and livestock pose a serious epidemiological threat and challenge the world's population. The SARS-CoV-2/COVID-19 pandemic has made the world aware of the scale of the threat. The surfaces of various materials can be a source of viruses that remain temporarily contagious in the environment. Few polymers have antiviral effects that reduce infectivity or the presence of a virus in the human environment. Some of the effects are due to certain physical properties, e.g., high hydrophobicity. Other materials owe their antiviral activity to a modified physicochemical structure favoring the action on specific virus receptors or on their biochemistry. Current research areas include: gluten, polyvinylidene fluoride, polyimide, polylactic acid, graphene oxide, and polyurethane bound to copper oxide. The future belongs to multi-component mixtures or very thin multilayer systems. The rational direction of research work is the search for materials with a balanced specificity in relation to the most dangerous viruses and universality in relation to other viruses.


Subject(s)
Antiviral Agents , COVID-19 , Polymers/pharmacology , Antiviral Agents/pharmacology , Humans
20.
Polim Med ; 50(2): 75-78, 2020.
Article in English | MEDLINE | ID: covidwho-1044274

ABSTRACT

Pathogenic viral factors pose a serious epidemiological threat and challenge to the world population, as proven by the scale and rapidity of COVID-19 pandemic outbreak. Polymer macromolecules can be an alternative to the accepted forms of treatment. Polymeric substances can be used as drugs or as adjuvants in vaccines. The most important feature of polymers is their advanced structure and the ability to construct the molecule from scratch, giving it the desired properties. Antiviral properties are influenced by, among other things, electrical charge, form and structure, and composition with other polymers or heavy metals. Depending on the expected properties, molecules can be built from scratch to be capable of transporting drugs or improve the effectiveness of the right drug. They can also be antiviral drugs in themselves. Polymeric compounds allow to reduce the frequency of adverse effects and improve the effect of the drug. They can have a direct antiviral effect by upsetting the lipid membrane of the surrounding viruses. Antiviral action of polymers occurs because of the properties of the polymers alone or in combination with other molecules. Viral epidemics are a motivation for research that can help stop a global pandemic in the future.


Subject(s)
Antiviral Agents , COVID-19 , Pharmaceutical Preparations , Polymers/chemistry , Antiviral Agents/therapeutic use , Drug Carriers/chemistry , Humans , Polymers/pharmacology
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