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1.
Adv Drug Deliv Rev ; 180: 114079, 2022 01.
Article in English | MEDLINE | ID: covidwho-1620432

ABSTRACT

Polyethylene glycol or PEG has a long history of use in medicine. Many conventional formulations utilize PEG as either an active ingredient or an excipient. PEG found its use in biotechnology therapeutics as a tool to slow down drug clearance and shield protein therapeutics from undesirable immunogenicity. Nanotechnology field applies PEG to create stealth drug carriers with prolonged circulation time and decreased recognition and clearance by the mononuclear phagocyte system (MPS). Most nanomedicines approved for clinical use and experimental nanotherapeutics contain PEG. Among the most recent successful examples are two mRNA-based COVID-19 vaccines that are delivered by PEGylated lipid nanoparticles. The breadth of PEG use in a wide variety of over the counter (OTC) medications as well as in drug products and vaccines stimulated research which uncovered that PEG is not as immunologically inert as it was initially expected. Herein, we review the current understanding of PEG's immunological properties and discuss them in the context of synthesis, biodistribution, safety, efficacy, and characterization of PEGylated nanomedicines. We also review the current knowledge about immunological compatibility of other polymers that are being actively investigated as PEG alternatives.


Subject(s)
Drug Carriers , Nanomedicine , Polyethylene Glycols/chemistry , Animals , COVID-19 Vaccines/chemistry , COVID-19 Vaccines/immunology , Drug Delivery Systems , Humans
2.
Front Biosci (Landmark Ed) ; 26(12): 1723-1736, 2021 12 30.
Article in English | MEDLINE | ID: covidwho-1614664

ABSTRACT

Thousands of drugs, nutraceuticals and their combinations can be used to select candidate therapeutics for targeting SARS-CoV-2 and its symptoms in order to curb COVID-19. A comprehensive, multi-level strategy against COVID-19 should include drug targeting of biomolecules and biochemical pathways involved in the prevention and proliferation of the infection, and the fatal or serious symptoms following infection. Several drugs are routinely used in the treatment of different categories of seriously ill COVID-19 patients including tocilizumab, remdesivir and dexamethasone. The current risk/benefit assessment supports the emergency testing and approval of more drugs. The process for new drug selection could be based on the identification of one drug for one target, or of a multi-potent drug for many targets and drug combinations for one or more targets, that can cause a substantial reduction in the high mortality rate of COVID-19. Several drugs have been identified that can fit this potential role by targeting different stages of COVID-19 including baricitinib, molnupiravir and PF-07321332/ritonavir and also the combination of deferiprone with N-acetylcysteine for inhibiting the vicious circle of oxidative stress toxicity and endothelial cell damage. Most of these drugs are expected to be effective against all the SARS-CoV-2 variants including Omicron (B.1.1.529) and also the associated COVID-19 complications.


Subject(s)
COVID-19 , SARS-CoV-2 , Antiviral Agents/therapeutic use , Drug Delivery Systems , Humans , Lactams , Leucine , Nitriles , Pandemics , Proline
3.
Int J Nanomedicine ; 16: 8141-8158, 2021.
Article in English | MEDLINE | ID: covidwho-1581579

ABSTRACT

Chitosan has been investigated in several biological fields, including drug and gene delivery, tissue engineering antiviral and immunological adjuvant methods. It's a cationic copolymer of N-acetyl glucosamine and D-glucosamine with different molecular chain lengths, compositions, and sequences than N-acetyl glucosamine and D-glucosamine. It is biocompatible and cyto-compatible, as well as recyclable and bioresorbable. As effective drug delivery methods, chitosan nanoparticles are shaped into several pathways. The purpose of this article is to provide an overview of its antiviral application as a nanocarrier for antiviral medications, highlighting the benefits, limitations, and downsides. In this review, we will report the most recent COVID-19 vaccination advances. It will also be discussed what the future holds for chitosan nanoparticles in the treatment of coronaviruses.


Subject(s)
COVID-19 , Chitosan , Nanoparticles , Antiviral Agents , COVID-19/drug therapy , COVID-19 Vaccines , Drug Carriers , Drug Delivery Systems , Humans , SARS-CoV-2
4.
Drug Deliv ; 29(1): 10-17, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1577575

ABSTRACT

Aerosol therapy is used to deliver medical therapeutics directly to the airways to treat respiratory conditions. A potential consequence of this form of treatment is the release of fugitive aerosols, both patient derived and medical, into the environment and the subsequent exposure of caregivers and bystanders to potential viral infections. This study examined the release of these fugitive aerosols during a standard aerosol therapy to a simulated adult patient. An aerosol holding chamber and mouthpiece were connected to a representative head model and breathing simulator. A combination of laser and Schlieren imaging was used to non-invasively visualize the release and dispersion of fugitive aerosol particles. Time-varying aerosol particle number concentrations and size distributions were measured with optical particle sizers at clinically relevant positions to the simulated patient. The influence of breathing pattern, normal and distressed, supplemental air flow, at 0.2 and 6 LPM, and the addition of a bacterial filter to the exhalation port of the mouthpiece were assessed. Images showed large quantities of fugitive aerosols emitted from the unfiltered mouthpiece. The images and particle counter data show that the addition of a bacterial filter limited the release of these fugitive aerosols, with the peak fugitive aerosol concentrations decreasing by 47.3-83.3%, depending on distance from the simulated patient. The addition of a bacterial filter to the mouthpiece significantly reduces the levels of fugitive aerosols emitted during a simulated aerosol therapy, p≤ .05, and would greatly aid in reducing healthcare worker and bystander exposure to potentially harmful fugitive aerosols.


Subject(s)
Aerosols , COVID-19 , Drug Delivery Systems , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Nebulizers and Vaporizers , Respiratory Therapy , Aerosols/administration & dosage , Aerosols/adverse effects , COVID-19/prevention & control , COVID-19/transmission , Computer Simulation , Drug Delivery Systems/instrumentation , Drug Delivery Systems/methods , Equipment Design , Humans , Infection Control/methods , Models, Biological , Particle Size , Respiratory Therapy/adverse effects , Respiratory Therapy/instrumentation , Respiratory Therapy/methods , SARS-CoV-2
5.
Sci Rep ; 11(1): 17263, 2021 08 26.
Article in English | MEDLINE | ID: covidwho-1550348

ABSTRACT

Dexamethasone (Dex) is a highly insoluble front-line drug used in cancer therapy. Data from clinical trials indicates that the pharmacokinetics of Dex vary considerably between patients and prolonging drug exposure rather than increasing absolute dose may improve efficacy. Non-toxic, fully biodegradable Dex loaded nanovectors (NV) were formulated, via simple direct hydration within 10 min, as a vehicle to extend exposure and distribution in vivo. Dex-NV were just as effective as the free drug against primary human leukemia cells in vitro and in vivo. Importantly, high levels of DMSO solvent were not required in the NV formulations. Broad distribution of NV was seen rapidly following inoculation into mice. NV accumulated in major organs, including bone marrow and brain, known sanctuary sites for ALL. The study describes a non-toxic, more easily scalable system for improving Dex solubility for use in cancer and can be applied to other medical conditions associated with inflammation.


Subject(s)
Dexamethasone/administration & dosage , Drug Delivery Systems/methods , Nanostructures/chemistry , Polymers/chemistry , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Xenograft Model Antitumor Assays/methods , Animals , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/chemistry , Antineoplastic Agents, Hormonal/pharmacokinetics , Child , Dexamethasone/chemistry , Dexamethasone/pharmacokinetics , Drug Liberation , Humans , Kaplan-Meier Estimate , Mice, Inbred NOD , Mice, Knockout , Mice, SCID , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Treatment Outcome , Tumor Cells, Cultured , Young Adult
6.
Int J Nanomedicine ; 16: 7391-7416, 2021.
Article in English | MEDLINE | ID: covidwho-1523545

ABSTRACT

Liposomes are ubiquitous tools in biomedical applications, such as drug delivery, membrane science and artificial cell. Micro- and nanofabrication techniques have revolutionized the preparation of liposomes on the microscale. State-of-the-art liposomal formation on microfluidic chips and its associated applications are introduced in this review. We attempt to provide a reference for liposomal researchers by comparing various microfluidic techniques for liposomes formation.


Subject(s)
Liposomes , Microfluidics , Drug Delivery Systems , Lipids
7.
Mater Sci Eng C Mater Biol Appl ; 116: 111260, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-1452344

ABSTRACT

Polymeric nanoparticulate systems allow the encapsulation of bio-active substances, giving them protection against external agents and increasing the drug's bioavailability. The use of biocompatible and biodegradable polymers usually guarantees the harmless character of the formulation, and a controlled drug release is also assured. A relatively easy procedure to obtain polymeric formulations of bioactive agents is ionotropic gelation, which allows the synthesis of chitosan (CS) - sodium tri-polyphosphate nanoparticles (NPs) loading encapsulated proteins. In this work, Bovine serum albumin (BSA) model protein and a recombinant porcine alpha interferon variant were used to obtain nanoparticulate formulations. The internalization of the encapsulated material by cells was studied using a BSA-fluorescein system; the fluorescent conjugate was observable inside the cells after 20 h of incubation. The therapeutic CS-alpha interferon formulation showed a maximum of protein released in vitro at around 90 h. This system was found to be safe in a cytotoxicity assay, while biological activity experiments in vitro showed antiviral protection of cells in the presence of encapsulated porcine alpha interferon. In vivo experiments in pigs revealed a significant and sustained antiviral response through overexpression of the antiviral markers OAS2 and PKR. This proves the preservation of porcine alpha interferon biological activity, and also that a lasting response was obtained. This procedure is an effective and safe method to formulate drugs in nanoparticulate systems, representing a significant contribution to the search for more effective drug delivery strategies.


Subject(s)
Chitosan , Nanoparticles , Pharmaceutical Preparations , Animals , Antiviral Agents/pharmacology , Biological Availability , Cattle , Drug Carriers , Drug Delivery Systems , Interferon-alpha , Particle Size , Polymers , Swine
8.
Indian J Pathol Microbiol ; 64(4): 771-775, 2021.
Article in English | MEDLINE | ID: covidwho-1485273

ABSTRACT

Context: The rapid outbreak of SARS-CoV-2 has become a significant global health concern, highlighting the dire need for antiviral therapeutic agents. RNA-dependent RNA polymerase (RdRp) of coronavirus plays crucial roles in RNA synthesis, and hence remains the druggable target for the treatment of this disease. The most potent broad-spectrum inhibitors of viral RdRp are members of nucleoside analogs (NAs). However, SARS-CoV-2 proved to be a challenging one for the novel NA drug designing strategy because coronavirus possesses an exonuclease (ExoN) domain that is capable of excising NAs, thus showing resistance to existing antiviral drugs. Aim: The objective of our study was to compare the SARS-CoV-2 exonuclease (nsp14) protein sequence of Wuhan-type virus with those of Indian SARS-Cov-2 isolates and to study the effect of multiple mutations on the secondary structure alterations of proteins. Subjects and Methods: Multiple-sequence alignment of exonuclease amino-acid sequences followed by phylogenetic analysis and prediction of its secondary structure of the protein was performed. Results: Altogether, seven mutations were detected in the nsp14 of Indian SARS-CoV-2 isolates. Subsequently, prediction of their secondary structures revealed that mutations altered the structural stability of exonuclease proteins. Conclusions: Present findings, therefore, further suggest that evolvability of SARS-CoV-2 is primarily associated with the onset of multiple novel mutations that rapidly spread at several new locations of the viral genome and also provides important insight to develop specific control strategies to fight against COVID-19 infections.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/genetics , Exonucleases/genetics , SARS-CoV-2/drug effects , SARS-CoV-2/genetics , Sequence Analysis, DNA , China , Drug Delivery Systems/methods , Genetic Variation , Genotype , Humans , India , Mutation , Phylogeny
9.
Sci Rep ; 11(1): 20687, 2021 10 19.
Article in English | MEDLINE | ID: covidwho-1475486

ABSTRACT

This analysis presents a systematic evaluation of the extent of therapeutic opportunities that can be obtained from drug repurposing by connecting drug targets with disease genes. When using FDA-approved indications as a reference level we found that drug repurposing can offer an average of an 11-fold increase in disease coverage, with the maximum number of diseases covered per drug being increased from 134 to 167 after extending the drug targets with their high confidence first neighbors. Additionally, by network analysis to connect drugs to disease modules we found that drugs on average target 4 disease modules, yet the similarity between disease modules targeted by the same drug is generally low and the maximum number of disease modules targeted per drug increases from 158 to 229 when drug targets are neighbor-extended. Moreover, our results highlight that drug repurposing is more dependent on target proteins being shared between diseases than on polypharmacological properties of drugs. We apply our drug repurposing and network module analysis to COVID-19 and show that Fostamatinib is the drug with the highest module coverage.


Subject(s)
COVID-19/drug therapy , Drug Repositioning/methods , Gene Regulatory Networks/drug effects , Protein Interaction Maps/genetics , SARS-CoV-2 , Antiviral Agents/pharmacology , Bayes Theorem , Computational Biology/methods , Drug Delivery Systems , Drug Discovery , Humans , Polypharmacology , Protein Interaction Mapping , United States , United States Food and Drug Administration
10.
Phytomedicine ; 90: 153651, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1454416

ABSTRACT

BACKGROUND: Although numerous medicinal herbal compounds demonstrate promising therapeutic potential, their clinical application is often limited by their poor oral bioavailability. To circumvent this barrier, various lipid-based herbal formulations have been developed and trialled with promising experimental results. PURPOSE: This scoping review aims to describe the effect of lipid-based formulations on the oral bioavailability of herbal compounds. METHODS: A systematic search was conducted across three electronic databases (Medline, Embase and Cochrane Library) between January 2010 and January 2021 to identify relevant studies. The articles were rigorously screened for eligibility. Data from eligible studies were then extracted and collated for synthesis and descriptive analysis using Covidence. RESULTS: A total of 109 studies were included in the present review: 105 animal studies and four clinical trials. Among the formulations investigated, 50% were emulsions, 34% lipid particulate systems, 12% vesicular systems, and 4% were other types of lipid-based formulations. Within the emulsion system classification, self-emulsifying drug delivery systems were observed to produce the best improvements in oral bioavailability, followed by mixed micellar formulations. The introduction of composite lipid-based formulations and the use of uncommon surfactants such as sodium oleate in emulsion preparation was shown to consistently enhance the bioavailability of herbal compounds with poor oral absorption. Interestingly, the lipid-based formulations of magnesium lithospermate B and Pulsatilla chinensis produced an absolute bioavailability greater than 100% indicating the possibility of prolonged systemic circulation. With respect to chemical conjugation, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was the most frequently used and significantly improved the bioavailability of its phytoconstituents. CONCLUSION: Our findings suggest that there is no distinct lipid-based formulation superior to the other. Bioavailability improvements were largely dependent on the nature of the phytoconstituents. This scoping review, however, provided a detailed summary of the most up-to-date evidence on phytoconstituents formulated into lipid preparations and their oral bioavailability. We conclude that a systematic review and meta-analysis between bioavailability improvements of individual phytoconstituents (such as kaempferol, morin and myricetin) in various lipid-based formulations will provide a more detailed association. Such a review will be highly beneficial for both researchers and herbal manufacturers.


Subject(s)
Biological Availability , Drug Delivery Systems , Micelles , Plant Preparations/pharmacokinetics , Surface-Active Agents , Administration, Oral , Animals , Emulsions , Humans , Lipids , Plant Preparations/administration & dosage , Solubility
11.
J Control Release ; 339: 361-380, 2021 11 10.
Article in English | MEDLINE | ID: covidwho-1454255

ABSTRACT

Fungal infections affect millions of people globally and are often unreceptive to conventional topical or oral preparations because of low drug bioavailability at the infection site, lack of sustained therapeutic effect, and the development of drug resistance. Amphotericin B (AmB) is one of the most potent antifungal agents. It is increasingly important since fungal co-infections associated with COVID-19 are frequently reported. AmB is only administered via injections (IV) and restricted to life-threatening infections due to its nephrotoxicity and administration-related side effects. In this work, we introduce, for the first time, dissolving microneedle patches (DMP) loaded with micronised particles of AmB to achieve localised and long-acting intradermal delivery of AmB for treatment of cutaneous fungal infections. AmB was pulverised with poly (vinyl alcohol) and poly (vinyl pyrrolidone) to form micronised particles-loaded gels, which were then cast into DMP moulds to form the tips. The mean particle size of AmB in AmB DMP tips after pulverisation was 1.67 ± 0.01 µm. This is an easy way to fabricate and load microparticles into DMP, as few steps are required, and no organic solvents are needed. AmB had no covalent chemical interaction with the excipients, but the crystallinity of AmB was reduced in the tips. AmB was completely released from the tips within 4 days in vitro. AmB DMP presented inhibition of Candida albicans (CA) and the killing rate of AmB DMP against CA biofilm inside porcine skin reached 100% within 24 h. AmB DMP were able to pierce excised neonatal porcine skin at an insertion depth of 301.34 ± 46.86 µm. Ex vivo dermatokinetic and drug deposition studies showed that AmB was mainly deposited in the dermis. An in vivo dermatokinetic study revealed that the area under curve (AUC0-inf) values of AmB DMP and IV (Fungizone® bolus injection 1 mg/kg) groups were 8823.0 d∙µg/g and 33.4 d∙µg/g, respectively (264-fold higher). AmB remained at high levels (219.07 ± 102.81 µg/g or more) in the skin until 7 days after the application of AmB DMP. Pharmacokinetic and biodistribution studies showed that AmB concentration in plasma, kidney, liver, and spleen in the AmB DMP group was significantly lower than that in the IV group. Accordingly, this system addressed the systemic side effects of intravenous injection of AmB and localised the drug inside the skin for a week. This work establishes a novel, easy and effective method for long-acting and localised intradermal drug delivery.


Subject(s)
Amphotericin B , COVID-19 , Animals , Antifungal Agents , Drug Delivery Systems , Humans , SARS-CoV-2 , Swine , Tissue Distribution
12.
Curr Top Med Chem ; 20(11): 915-962, 2020.
Article in English | MEDLINE | ID: covidwho-1453165

ABSTRACT

BACKGROUND: Emerging viral zoonotic diseases are one of the major obstacles to secure the "One Health" concept under the current scenario. Current prophylactic, diagnostic and therapeutic approaches often associated with certain limitations and thus proved to be insufficient for customizing rapid and efficient combating strategy against the highly transmissible pathogenic infectious agents leading to the disastrous socio-economic outcome. Moreover, most of the viral zoonoses originate from the wildlife and poor knowledge about the global virome database renders it difficult to predict future outbreaks. Thus, alternative management strategy in terms of improved prophylactic vaccines and their delivery systems; rapid and efficient diagnostics and effective targeted therapeutics are the need of the hour. METHODS: Structured literature search has been performed with specific keywords in bibliographic databases for the accumulation of information regarding current nanomedicine interventions along with standard books for basic virology inputs. RESULTS: Multi-arrayed applications of nanomedicine have proved to be an effective alternative in all the aspects regarding the prevention, diagnosis, and control of zoonotic viral diseases. The current review is focused to outline the applications of nanomaterials as anti-viral vaccines or vaccine/drug delivery systems, diagnostics and directly acting therapeutic agents in combating the important zoonotic viral diseases in the recent scenario along with their potential benefits, challenges and prospects to design successful control strategies. CONCLUSION: This review provides significant introspection towards the multi-arrayed applications of nanomedicine to combat several important zoonotic viral diseases.


Subject(s)
Drug Delivery Systems/methods , Viral Vaccines/chemistry , Viral Zoonoses/diagnosis , Viral Zoonoses/prevention & control , Viral Zoonoses/therapy , Viruses/drug effects , Animals , Animals, Wild , Biosensing Techniques , Drug Carriers/chemistry , Drug Compounding , Drug Liberation , Humans , Nanomedicine , Nanoparticles/chemistry , Polymers/chemistry , Polymers/metabolism , Transfection , Viruses/metabolism
13.
Biomed Pharmacother ; 144: 112247, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1446461

ABSTRACT

COVID-19 is a pneumonia-like disease with highly transmittable and pathogenic properties caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which infects both animals and humans. Although many efforts are currently underway to test possible therapies, there is no specific FDA approved drug against SARS-CoV-2 yet. miRNA-directed gene regulation controls the majority of biological processes. In addition, the development and progression of several human diseases are associated with dysregulation of miRNAs. In this regard, it has been shown that changes in miRNAs are linked to severity of COVID-19 especially in patients with respiratory diseases, diabetes, heart failure or kidney problems. Therefore, targeting these small noncoding-RNAs could potentially alleviate complications from COVID-19. Here, we will review the roles and importance of host and RNA virus encoded miRNAs in COVID-19 pathogenicity and immune response. Then, we focus on potential miRNA therapeutics in the patients who are at increased risk for severe disease.


Subject(s)
Antiviral Agents/administration & dosage , COVID-19/therapy , Genetic Therapy/methods , MicroRNAs/administration & dosage , Animals , Antiviral Agents/immunology , COVID-19/genetics , COVID-19/immunology , Drug Delivery Systems/methods , Humans , MicroRNAs/genetics , MicroRNAs/immunology
14.
Ther Deliv ; 12(10): 685-691, 2021 10.
Article in English | MEDLINE | ID: covidwho-1439631
15.
Nat Rev Microbiol ; 19(11): 685-700, 2021 11.
Article in English | MEDLINE | ID: covidwho-1428872

ABSTRACT

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an unprecedented global health crisis. However, therapeutic options for treatment are still very limited. The development of drugs that target vital proteins in the viral life cycle is a feasible approach for treating COVID-19. Belonging to the subfamily Orthocoronavirinae with the largest RNA genome, SARS-CoV-2 encodes a total of 29 proteins. These non-structural, structural and accessory proteins participate in entry into host cells, genome replication and transcription, and viral assembly and release. SARS-CoV-2 proteins can individually perform essential physiological roles, be components of the viral replication machinery or interact with numerous host cellular factors. In this Review, we delineate the structural features of SARS-CoV-2 from the whole viral particle to the individual viral proteins and discuss their functions as well as their potential as targets for therapeutic interventions.


Subject(s)
COVID-19/drug therapy , SARS-CoV-2/chemistry , Viral Proteins/chemistry , COVID-19/virology , Drug Delivery Systems , Genome, Viral , SARS-CoV-2/drug effects , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Viral Proteins/genetics
16.
Cells ; 10(9)2021 09 15.
Article in English | MEDLINE | ID: covidwho-1408625

ABSTRACT

Coronavirus disease 19 (COVID-19) is caused by an enveloped, positive-sense, single-stranded RNA virus, referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which belongs to the realm Riboviria, order Nidovirales, family Coronaviridae, genus Betacoronavirus and the species Severe acute respiratory syndrome-related coronavirus. This viral disease is characterized by a myriad of varying symptoms, such as pyrexia, cough, hemoptysis, dyspnoea, diarrhea, muscle soreness, dysosmia, lymphopenia and dysgeusia amongst others. The virus mainly infects humans, various other mammals, avian species and some other companion livestock. SARS-CoV-2 cellular entry is primarily accomplished by molecular interaction between the virus's spike (S) protein and the host cell surface receptor, angiotensin-converting enzyme 2 (ACE2), although other host cell-associated receptors/factors, such as neuropilin 1 (NRP-1) and neuropilin 2 (NRP-2), C-type lectin receptors (CLRs), as well as proteases such as TMPRSS2 (transmembrane serine protease 2) and furin, might also play a crucial role in infection, tropism, pathogenesis and clinical outcome. Furthermore, several structural and non-structural proteins of the virus themselves are very critical in determining the clinical outcome following infection. Considering such critical role(s) of the abovementioned host cell receptors, associated proteases/factors and virus structural/non-structural proteins (NSPs), it may be quite prudent to therapeutically target them through a multipronged clinical regimen to combat the disease.


Subject(s)
COVID-19 , Host Microbial Interactions , SARS-CoV-2/pathogenicity , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/pathology , COVID-19/virology , Drug Delivery Systems , Furin/chemistry , Furin/metabolism , Humans , Lectins, C-Type/chemistry , Lectins, C-Type/metabolism , Molecular Structure , Neuropilins/chemistry , Neuropilins/metabolism , Peptidyl-Dipeptidase A/chemistry , Peptidyl-Dipeptidase A/metabolism , Protein Binding , Receptors, Virus/chemistry , Receptors, Virus/metabolism , Serine Endopeptidases/chemistry , Serine Endopeptidases/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Treatment Outcome , Viral Nonstructural Proteins/chemistry , Viral Nonstructural Proteins/metabolism , Virus Internalization
17.
Int J Biol Macromol ; 190: 636-648, 2021 Nov 01.
Article in English | MEDLINE | ID: covidwho-1401500

ABSTRACT

SARS-CoV-2 nucleocapsid (N) protein undergoes RNA-induced phase separation (LLPS) and sequesters the host key stress granule (SG) proteins, Ras-GTPase-activating protein SH3-domain-binding protein 1 and 2 (G3BP1 and G3BP2) to inhibit SG formation. This will allow viral packaging and propagation in host cells. Based on a genomic-guided meta-analysis, here we identify upstream regulatory elements modulating the expression of G3BP1 and G3BP2 (collectively called G3BP1/2). Using this strategy, we have identified FOXA1, YY1, SYK, E2F-1, and TGFBR2 as activators and SIN3A, SRF, and AKT-1 as repressors of G3BP1/2 genes. Panels of the activators and repressors were then used to identify drugs that change their gene expression signatures. Two drugs, imatinib, and decitabine have been identified as putative modulators of G3BP1/2 genes and their regulators, suggesting their role as COVID-19 mitigation agents. Molecular docking analysis suggests that both drugs bind to G3BP1/2 with a much higher affinity than the SARS-CoV-2 N protein. This study reports imatinib and decitabine as candidate drugs against N protein and G3BP1/2 protein.


Subject(s)
Adaptor Proteins, Signal Transducing/chemistry , COVID-19/drug therapy , Coronavirus Nucleocapsid Proteins/chemistry , DNA Helicases/chemistry , Decitabine/chemistry , Imatinib Mesylate/chemistry , Molecular Docking Simulation , Molecular Dynamics Simulation , Poly-ADP-Ribose Binding Proteins/chemistry , RNA Helicases/chemistry , RNA Recognition Motif Proteins/chemistry , RNA-Binding Proteins/chemistry , SARS-CoV-2/chemistry , Adaptor Proteins, Signal Transducing/antagonists & inhibitors , Adaptor Proteins, Signal Transducing/metabolism , COVID-19/metabolism , Coronavirus Nucleocapsid Proteins/metabolism , DNA Helicases/antagonists & inhibitors , DNA Helicases/metabolism , Decitabine/pharmacology , Drug Delivery Systems , Genomics , Imatinib Mesylate/pharmacology , Phosphoproteins/chemistry , Phosphoproteins/metabolism , Poly-ADP-Ribose Binding Proteins/antagonists & inhibitors , Poly-ADP-Ribose Binding Proteins/metabolism , RNA Helicases/antagonists & inhibitors , RNA Helicases/metabolism , RNA Recognition Motif Proteins/antagonists & inhibitors , RNA Recognition Motif Proteins/metabolism , RNA-Binding Proteins/antagonists & inhibitors , RNA-Binding Proteins/metabolism , SARS-CoV-2/metabolism
18.
Biomed Pharmacother ; 143: 112162, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1401248

ABSTRACT

BACKGROUND: The global healthcare sector has been dealing with a situation known as a novel severe acute respiratory syndrome (SARS-CoV-2) since the end of 2019. Covid-19 is an acronym for Covid-19 (Coronavirus Disease- 2019). It causes a respiratory infection that includes cold, sneezing and coughing, and pneumonia. In the case of an animal, it causes diarrhea and upper respiratory diseases. Covid-19 transmitted human to human via airborne droplets. First Covid-19 emerged in Wuhan market China and it spread rapidly throughout the World. As we know nanoparticles are a novel drug delivery system. They have various advantageous effects like increasing the efficacy of the drug, safety, etc. In this review, we study about the nanoparticles and summarize how it is effective during drug delivery system in Covid-19. Chitosan is a much focused biopolymeric nanoparticle. It delivers drugs to the specific target site. In a recent health crisis, chitosan nanoparticles are one of the ways to release drugs of Covid-19, and specifically in the lungs of the affected patients. We studied and extracted our data from various research papers, review papers, and some other articles. OBJECTIVE: The main goal is to study the nanoparticles and their future aspects which is an effective drug delivery system in Covid-19. METHODS: The bibliographic search was done through a systematic search. The terms "Nanoparticles", "Covid-19 ", "Drug delivery" etc. were used to search the databases/search engines like "Google Scholar", "NCBI", "PubMed", "Science Direct" etc. These databases and search engines used here perform the limited criteria of search to conduct a systematic literature survey for the study and report writing. All the text from the articles and research papers were studied and analyzed. The various articles and research papers were used in writing this report and all of which are mentioned in the reference section of this report. CONCLUSION: Our current studies reveal that nanoparticles may prove very helpful in the delivery of drugs for Covid-19 treatment. Many cases showed that patients, where drugs are delivered with the help of nanoparticles, produced very few side effects.


Subject(s)
COVID-19/drug therapy , Nanoparticles , Animals , Biopolymers/adverse effects , Biopolymers/chemistry , Biopolymers/therapeutic use , COVID-19/virology , Drug Delivery Systems/methods , Humans , Nanomedicine , Nanoparticles/adverse effects , Nanoparticles/chemistry , SARS-CoV-2/pathogenicity
20.
Int J Mol Sci ; 22(14)2021 Jul 16.
Article in English | MEDLINE | ID: covidwho-1389404

ABSTRACT

In the past few years, Bruton's tyrosine Kinase (Btk) has emerged as new target in medicinal chemistry. Since approval of ibrutinib in 2013 for treatment of different hematological cancers (as leukemias and lymphomas), two other irreversible Btk inhibitors have been launched on the market. In the attempt to overcome irreversible Btk inhibitor limitations, reversible compounds have been developed and are currently under evaluation. In recent years, many Btk inhibitors have been patented and reported in the literature. In this review, we summarized the (ir)reversible Btk inhibitors recently developed and studied clinical trials and preclinical investigations for malignancies, chronic inflammation conditions and SARS-CoV-2 infection, covering advances in the field of medicinal chemistry. Furthermore, the nanoformulations studied to increase ibrutinib bioavailability are reported.


Subject(s)
Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors , Protein Kinase Inhibitors/administration & dosage , Adenine/administration & dosage , Adenine/analogs & derivatives , Agammaglobulinaemia Tyrosine Kinase/metabolism , COVID-19/drug therapy , Chemistry, Pharmaceutical/methods , Drug Delivery Systems/methods , Hematologic Neoplasms/drug therapy , Humans , Inflammation/drug therapy , Neoplasms/drug therapy , Piperidines/administration & dosage , Protein-Tyrosine Kinases/antagonists & inhibitors , Pyrimidines/administration & dosage , SARS-CoV-2/drug effects
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