Drug Repurposing for, ENT and Head and Neck, Infectious and Oncologic Diseases: Current Practices and Future Possibilities

The specialty of otolaryngology and head and neck surgery involves various subspecialties, encompassing clinical conditions ranging from medical to surgical issues in infections, noninfectious benign conditions and various benign and malignant tumors. Drug repurposing has proven to be significant in multiple fields and is still investigational in many promising possible solutions to different clinical challenges in this specialty. We discuss some classes of drugs that have been successfully repurposed for ENT pathologies. We also discuss the novel research goals that are being pursued in our department in the context of drug repurposing for airway infectious diseases including COVID-10 and mucormycosis. There has been a silent and underappreciated rise in drug-resistant invasive fungal infections (IFIs). Emerging Mucorales are difficult to diagnose and tolerant to many of the frontline antifungal therapies. There is an urgent need to combat these emerging pathogens and investigate the molecular mechanisms underlying their potentiated virulence traits to identify potential therapeutic targets susceptible to anti-fungal compounds. The drug development process for IFIs remains largely expensive, and is inherently risky. These challenges declare an urgent need for discovery of new antifungal drugs and encourage drug repurposing as alternative approach to fungal control. The understanding of molecular underpinnings behind fungi and human host continue to grow, however, further research endeavors are underway to fully explore the fungal pathogenesis, (including the role of iron) to gather new insights to achieve improved therapeutics. Above all, creative screening tools and out-of-the-box ideas aimed at increasing the possibility of identifying potential first-in-class antifungals are highly encouraged. The recently emerging fungal co-infections in the COVID-19 disease patients has revived the interest in the pathophysiology and clinical management of the IFIs, and identification of potential druggable nodes in olfactory niche to inhibit the spread of COVID-19 and associated co-infections by leveraging in vitro-disease models of host-pathogen interaction. We employed our recently established COVID-19 disease model to decipher potential anti-metabolic molecules that can be repurposed as novel bilateral drugs having anti-fungal and host-directed features with extended applicability in diabetes, COVID-19, and mucormycosis with and without COVID-19. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023.

Nasal spray of an IgM-like ACE2 fusion protein HH-120 accelerates SARS-CoV-2 clearance: A single-center propensity score-matched cohort study.

HH-120, a recently developed IgM-like ACE2 fusion protein with broad-spectrum neutralizing activity against all ACE2-utilizing coronaviruses, has been developed as a nasal spray for use as an early treatment agent to reduce disease progression and airborne transmission. The objective of this study was to evaluate the safety and efficacy of the HH-120 nasal spray in SARS-CoV-2-infected subjects. Eligible symptomatic or asymptomatic SARS-CoV-2-infected participants were enrolled in a single-arm trial to receive the HH-120 nasal spray for no longer than 6 days or until viral clearance at a single hospital between August 3 and October 7, 2022. An external control was built from real-world data of SARS-CoV-2-infected subjects contemporaneously hospitalized in the same hospital using a propensity score matching (PSM) method. After PSM, 65 participants in the HH-120 group and 103 subjects with comparable baseline characteristics in the external control group were identified. The viral clearance time was significantly shorter in participants receiving the HH-120 nasal spray than that in subjects of the control group (median 8 days vs. 10 days, p < 0.001); the difference was more prominent in those subgroup subjects with higher baseline viral load (median 7.5 days vs. 10.5 days, p < 0.001). The incidence of treatment-emergent adverse events and treatment-related adverse events of HH-120 group were 35.1% (27/77) and 3.9% (3/77), respectively. All the adverse events observed were mild, being of CTCAE grade 1 or 2, and transient. The HH-120 nasal spray showed a favorable safety profile and promising antiviral efficacy in SARS-CoV-2-infected subjects. The results from this study warrant further assessment of the efficacy and safety of the HH-120 nasal spray in large-scale randomized controlled clinical trials.

Comparison of the immunogenicity of nasal-spray rVSV vector, adenovirus vector, and inactivated COVID-19-based vaccines in rodent models.

Intranasal (i.n.) vaccines can induce mucosal and systemic immunity against respiratory pathogens. Previously, we demonstrated that the recombinant vesicular stomatitis virus (rVSV)-based COVID-19 vaccine rVSV-SARS-CoV-2, with poor immunogenicity via the intramuscular route (i.m.), is more suitable for i.n. administration in mice and nonhuman primates. Here, we found that the rVSV-SARS-CoV-2 Beta variant was more immunogenic than the wild-type strain and other variants of concern (VOCs) in golden Syrian hamsters. Furthermore, the immune responses elicited by rVSV-based vaccine candidates via the i.n. route were significantly higher than those of two licensed vaccines: the inactivated vaccine KCONVAC delivered via the i.m. route and the adenovirus-based Vaxzevria delivered i.n. or i.m. We next assessed the booster efficacy of rVSV following two i.m. doses of KCONVAC. Twenty-eight days after receiving two i.m. doses of KCONVAC, hamsters were boosted with a third dose of KCONVAC (i.m.), Vaxzevria (i.m. or i.n.), or rVSVs (i.n.). Consistent with other heterologous booster studies, Vaxzevria and rVSV elicited significantly higher humoral immunity than the homogenous KCONVAC. In summary, our results confirmed that two i.n. doses of rVSV-Beta elicited significantly higher humoral immune responses than commercial inactivated and adeno-based COVID vaccines in hamsters. As a heterologous booster dose, rVSV-Beta induced potent, persistent, and broad-spectrum humoral and mucosal neutralizing responses against all VOCs, highlighting its potential to be developed into a nasal-spray vaccine.

PHASE 1 CLINICAL TRIALS OF A Q-GRIFFITHSIN NASAL SPRAY FOR SARS-CoV-2 PROPHYLAXIS

Background: The currently approved vaccines do not induce sterilizing immunity against SAR-CoV-2 infection, and immunity wanes over time. A robust broad spectrum topical prophylaxis strategy could protect vulnerable populations in the face of continuous evolution of SARS-CoV-2. The algal antiviral lectin Griffithsin (GRFT), and an engineered oxidation-resistant variant Q-GRFT have robust entry inhibitory activity against SARS-CoV variants of concern, in addition to other respiratory viruses with pandemic potential. We designed a nasal spray to deliver Q-GRFT to the upper respiratory tract mucosa for on-demand use as a broad-spectrum prophylactic. Two clinical trials (Phase 1a and 1b) were conducted to assess safety, tolerability, and pharmacokinetics of Q-GRFT nasal spray in healthy adults. Method(s): Healthy adult volunteers were enrolled in a Phase 1a double blinded, randomized study to receive a single dose of either intranasal Q-GRFT (3.0 mg, 2 sprays per nostril) or placebo at 2:1 ratio. Following a safety review, the Phase 1b study was initiated. Eleven volunteers in Group 1 received 3.0 mg dose once daily, for 7 days. After a safety review, 11 volunteers in Group 2 received a total of 6.0 mg Q-GRFT (3.0 mg twice daily for 7 days). Topical Q-GRFT concentrations were measured by ELISA in collected nasal and nasopharyngeal fluids. Drug levels in plasma were assayed to determine systemic exposure. Viral microneutralization cytopathic effect (CPE) assays were performed against SARS-CoV-2 Omicron BA-5 and MERS-CoV. Result(s): Eighteen adults (24-54 years;Males 58.3%, Females 41.7%;12 Q-GRFT, 6 Placebo), and 22 adults (aged 23-59 years;Males 52.4%, Females 47.6%) were enrolled in Phase 1a and 1b, respectively. In Phase 1a, a single dose of Q-GRFT maintained quantifiable levels in nasal passages and nasopharynx for up to 24 hours. Similarly, Q-GRFT was quantifiable in nasal and nasopharyngeal regions in the Phase 1b study. No dose accumulation effect or systemic exposure was observed. Nasal and nasopharyngeal swab eluates inhibited SARS-CoV-2 Omicron BA.5 and MERS-CoV in CPE assays. Q-GRFT did not modify olfactory sensation. No severe adverse events were reported. Thus, the nasal spray was deemed safe. Conclusion(s): Intranasal Q-GRFT was safe and enhanced mucosal SARSCoV-2 inhibitory activity in human volunteers. The results support further development of Q-GRFT as a broad-spectrum prophylactic against coronaviruses to curb ongoing infections, and for future pandemic preparedness.

Aqueous cannabidiol ß-cyclodextrin complexed polymeric micelle nasal spray to attenuate in vitro and ex vivo SARS-CoV-2-induced cytokine storms.

Cannabidiol (CBD) has a number of biological effects by acting on the cannabinoid receptors CB1 and CB2. CBD may be involved in anti-inflammatory processes via CB1 and CB2 receptors, resulting in a decrease of pro-inflammatory cytokines. However, CBD's poor aqueous solubility is a major issue in pharmaceutical applications. The aim of the present study was to develop and evaluate a CBD nasal spray solution. A water-soluble CBD was prepared by complexation with ß-cyclodextrin (ß-CD) at a stoichiometric ratio of 1:1 and forming polymeric micelles using poloxamer 407. The mixture was then lyophilized and characterized using FT-IR, DSC, and TGA. CBD-ß-CD complex-polymeric micelles were formulated for nasal spray drug delivery. The physicochemical properties of the CBD-ß-CD complex-polymeric micelle nasal spray solution (CBD-ß-CDPM-NS) were assessed. The results showed that the CBD content in the CBD-ß-CD complex polymeric micelle powder was 102.1 ± 0.5% labeled claim. The CBD-ß-CDPM-NS was a clear colorless isotonic solution. The particle size, zeta potential, pH value, and viscosity were 111.9 ± 0.7 nm, 0.8 ± 0.1 mV, 6.02 ± 0.02, and 12.04 ± 2.64 cP, respectively. This formulation was stable over six months at ambient temperature. The CBD from CBD-ß-CDPM-NS rapidly released to 100% within 1 min. Ex vivo permeation studies of CBD-ß-CDPM-NS through porcine nasal mucosa revealed a permeation rate of 4.8 µg/cm2/min, which indicated that CBD was effective in penetrating nasal epithelial cells. CBD-ß-CDPM-NS was tested for its efficacy and safety in terms of cytokine production from nasal immune cells and toxicity to nasal epithelial cells. The CBD-ß-CDPM-NS was not toxic to nasal epithelial at the concentration of CBD equivalent to 3.125-50 µg/mL. When the formulation was subjected to bioactivity testing against monocyte-like macrophage cells, it proved that the CBD-ß-CDPM-NS has the potential to inhibit inflammatory cytokines. CBD-ß-CDPM-NS demonstrated the formulation's ability to reduce the cytokine produced by S-RBD stimulation in ex vivo porcine nasal mucosa in both preventative and therapeutic modes.

Synthesis of the first remdesivir cocrystal: design, characterization, and therapeutic potential for pulmonary delivery.

While cocrystal engineering is an emerging formulation strategy to overcome drug delivery challenges, its therapeutic potential in non-oral applications remains not thoroughly explored. We herein report for the first time the successful synthesis of a cocrystal for remdesivir (RDV), an antiviral drug with broad-spectrum activities against RNA viruses. The RDV cocrystal was prepared with salicylic acid (SA) via combined liquid-assisted grinding (LAG) and thermal annealing. Formation of RDV-SA was found to be a thermally activated process, where annealing at high temperature after grinding was a prerequisite to facilitate the cocrystal growth from an amorphous intermediate, rendering it elusive under ambient preparing conditions. Through powder X-ray analysis with Rietveld refinement, the three-dimensional molecular structure of RDV-SA was resolved. The thermally annealed RDV-SA produced by LAG crystalized in a non-centrosymmetric monoclinic space group P21 with a unit cell volume of 1826.53(17) Å3, accommodating one pair of RDV and SA molecules in the asymmetric unit. The cocrystal formation was also characterized by differential scanning calorimetry, solid-state nuclear magnetic resonance, and Fourier-transform infrared spectroscopy. RDV-SA was further developed as inhaled dry powders by spray drying for potential COVID-19 therapy. The optimized RDV-SA dry powders exhibited a mass median aerodynamic diameter of 4.33 ± 0.2 µm and fine particle fraction of 41.39 ± 4.25 %, indicating the suitability for pulmonary delivery. Compared with the raw RDV, RDV-SA displayed a 15.43-fold higher fraction of release in simulated lung fluid at 120 min (p = 0.0003). RDV-SA was safe in A549 cells without any in vitro cytotoxicity observed in the RDV concentration from 0.05 to 10 µM.

Virucidal Effect of Povidone Iodine on SARS-CoV-2 in Nasopharynx: An Open-label Randomized Clinical Trial.

To assess the virucidal effect of povidone iodine (PVP-I) on severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) located in the nasopharynx and suitable dose-formulation for nasal application were the purpose of this clinical trial. This single-center, open-label randomized clinical trial with a 7-arm parallel-group design was conducted in Dhaka Medical College (DMC) Hospital. A total of 189 reverse transcription-polymerase chain reaction (RT-PCR)-confirmed SARS CoV-2 positive cases aged 12-90 years with symptoms was sequentially enrolled following randomization. Nasopharyngeal clearance of SARS-CoV-2 was tested against PVP-I nasal irrigation (NI) at diluted concentrations of 0.4%, 0.5% and 0.6%, and PVP-I nasal spray (NS) at diluted concentrations of 0.5% and 0.6%. All groups were compared to the corresponding controls (distilled water). Written informed consent was ensured before participation. All procedures were conducted in after ethical clearance from the Ethical Review Board and in accordance with the Declaration of Helsinki. Viral clearance in a repeat RT-PCR (qualitative) was the primary outcome, and occurrence of any adverse event following administration of testing drug was considered as the secondary outcome. Analysis was performed using SPSS (Version 26). All cases were randomized into seven groups and each group consists of 27-patient. Mean age of the cases 43.98 ± 12.67 years (SD). All strength of NI were effective in nasopharyngeal clearance compared to the control (0.4%, p = 0.006; 0.5%, p < 0.001; and 0.6%, p = 0.018). Similarly, all strength of the NS is also effective than control (0.5%, p = < 0.001; and 0.6%, p ≤ 0.001). Highest nasopharyngeal clearance was observed in patients using 0.5% NI (n = 25, 92.6%, p = 0.018). Nasal irritation was the single most adverse event recorded in this trial and found in two patients using 0.4%, and 0.6% PVP-I NI, respectively. Both PVP-I NS and NI are effective for nasopharyngeal clearance in-vivo. However, further community trials are needed to repurpose these solutions as preventive agents against SARS-CoV2. Ethical clearance memo no ERC-DMC/ECC/2020/93. Trial registration NCT Identifier number NCT04549376. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-022-03106-0.

Spectacular voyage of droplets: Gas turbines to SARS-CoV-2

I will provide an account of the interesting dynamics exhibited by droplets at multiple length and time scales in completely different domains, namely gas turbines and COVID-19. In the first part of my talk, I will discuss how the spread of COVID can happen through respiratory droplets and fomites. In this part, I will provide a detailed exposition of how respiratory droplet dynamics can be combined with a pandemic model to provide a first principle insights into infection spread rates. We will show through experiments using surrogate fluids how such models can be experimentally verified rigorously. Subsequently, I will show how fomites form and how the virions are embedded in the crystal network using both contact free as well as sessile droplets. In the second part of my talk, I will provide some insights into the dynamics of spray-swirl interaction with a particular focus on droplet transport, breakup and dispersion. I will show how the fundamental insights gained through such interactions can be used to design a new class of atomizers in gas turbines.

Efficacy evaluation of an air-assisted electrostatic disinfection device for the effective disinfection and sanitization against the spread of pathogenic infections

This research aims to check the chargeability of sodium hypochlorite and the efficacy evaluation of an air-assisted electrostatic disinfection device. Five different inanimate surfaces i.e., wood, glass, stainless steel, plastic and fabric were considered to examine the performance in terms of efficacy, survival time, off-target losses, spray coverage and the volume of disinfectant consumed. A significant charge-to-mass level of 2.43 mC/kg was achieved for sodium hypochlorite at an applied voltage of 2.0 kV, a liquid flowrate of 253 ml/min and applied air pressure of 4.0 bar. The experimental results found that 1000 mg/L of sodium hypochlorite concentration effectively eliminated Pseudomonas aeruginosa, Clostridium perfringens and Bacteriophage MS2 colonies. © 2023 Elsevier B.V.

Automatic Boot Spray Machine: A Preventive Measure Against Corona Virus

Corona Virus (COVID-19) has already done havoc in the world. More than six hundred million people suffered from this virus and six million people are dead amongst them in the world. In Bangladesh, two million people have tested positive and approximately 30 thousand people are dead. SARS-CoV-2 virus causes this infectious corona disease. When an infected individual sneezes, coughs, speaks, or breathes, the virus is disseminated from their mouth or nose. One can also be infected by touching contaminated surface and spreads more in indoor environment. So, it has taught us the necessity of washing and sanitizing in our daily affairs. Automatic boot spray machine is a very practical and useful instrument to fight against the corona virus. This contact free spray machine helps to sanitize the boot without getting in contact with the surface and ultimately helps to prevent the spread of corona virus. The purpose of this essay is to create a boot sprayer that automatically releases soapy water. At a distance of meters, an obstruction sensor is employed to identify the heat and presence of the boot. A p-n-p transistor is used to operate the machine. This machine works perfectly at a distance of 2-30cm. It also provides good sensitivity percentage. This setup is user convenient and it saves money and power. © 2023 IEEE.

Extraction of niclosamide from commercial approved tablets into aqueous buffered solution creates potentially approvable oral and nasal sprays against COVID-19 and other respiratory infections.

Motivation: The low solubility, weak acid drug, niclosamide is a host cell modulator with broad-spectrum anti-viral cell-activity against many viruses, including stopping the SARS-CoV-2 virus from infecting cells in cell culture. As a result, a simple universal nasal spray preventative was proposed and investigated in earlier work regarding the dissolution of niclosamide into simple buffers. However, starting with pharmaceutical grade, niclosamide represents a new 505(b)(2) application. The motivation for this second paper in the series was therefore to explore if and to what extent niclosamide could be extracted from commercially available and regulatory-approved niclosamide oral tablets that could serve as a preventative nasal spray and an early treatment oral/throat spray, with possibly more expeditious testing and regulatory approval. Experimental: Measurements of supernatant niclosamide concentrations were made by calibrated UV-Vis for the dissolution of niclosamide from commercially available Yomesan crushed into a powder for dissolution into Tris Buffer (TB) solutions. Parameters tested were as follows: time (0-2 days), concentration (300 µM to -1 mM), pH (7.41 to 9.35), and anhydrous/hydrated state. Optical microscopy was used to view the morphologies of the initial crushed powder, and the dissolving and equilibrating undissolved excess particles to detect morphologic changes that might occur. Results: Concentration dependence: Niclosamide was readily extracted from powdered Yomesan at pH 9.34 TB at starting Yomesan niclosamide equivalents concentrations of 300 µM, 600 µM, and 1 mM. Peak dissolved niclosamide supernatant concentrations of 264 µM, 216 µM, and 172 µM were achieved in 1 h, 1 h, and 3 h respectively. These peaks though were followed by a reduction in supernatant concentration to an average of 112.3 µM ± 28.4 µM after overnight stir on day 2. pH dependence: For nominal pHs of 7.41, 8.35, 8.85, and 9.35, peak niclosamide concentrations were 4 µM, 22.4 µM, 96.2 µM, and 215.8 µM, respectively. Similarly, the day 2 values all reduced to 3 µM, 12.9 µM, 35.1 µM, and 112.3 µM. A heat-treatment to 200 °C dehydrated the niclosamide and showed a high 3 h concentration (262 µM) and the least day-2 reduction (to 229 µM). This indicated that the presence, or formation during exposure to buffer, of lower solubility polymorphs was responsible for the reductions in total solubilities. These morphologic changes were confirmed by optical microscopy that showed initially featureless particulate-aggregates of niclosamide could grow multiple needle-shaped crystals and form needle masses, especially in the presence of Tris-buffered sodium chloride, where new red needles were rapidly made. Scale up: A scaled-up 1 L solution of niclosamide was made achieving 165 µM supernatant niclosamide in 3 h by dissolution of just one fifth (100 mg niclosamide) of a Yomesan tablet. Conclusion: These comprehensive results provide a guide as to how to utilize commercially available and approved tablets of niclosamide to generate aqueous niclosamide solutions from a simple dissolution protocol. As shown here, just one 4-tablet pack of Yomesan could readily make 165 L of a 20 µM niclosamide solution giving 16,500 10 mL bottles. One million bottles, from just 60 packs of Yomesan, would provide 100 million single spray doses for distribution to mitigate a host of respiratory infections as a universal preventative-nasal and early treatment oral/throat sprays throughout the world. Graphical Abstract: pH dependence of niclosamide extraction from crushed Yomesan tablet material into Tris buffer (yellow-green in vial) and Tris-buffered saline solution (orange-red in vial). Initial anhydrous dissolution concentration is reduced by overnight stirring to likely monohydrate niclosamide; and is even lower if in TBSS forming new niclosamide sodium needle crystals grown from the original particles. Supplementary Information: The online version contains supplementary material available at 10.1186/s41120-023-00072-x.

Neutralisation of SARS-CoV-2 by monoclonal antibody through dual targeting powder formulation.

Neutralising monoclonal antibody (mAb) is an important weapon in our arsenal for combating respiratory viral infections. However, the effectiveness of neutralising mAb has been impeded by the rapid emergence of mutant variants. Early administration of broad-spectrum mAb with improved delivery efficiency can potentially enhance efficacy and patient outcomes. WKS13 is a humanised mAb which was previously demonstrated to exhibit broad-spectrum activity against SARS-CoV-2 variants. In this study, a dual targeting formulation strategy was designed to deliver WKS13 to both the nasal cavity and lower airways, the two critical sites of infection caused by SARS-CoV-2. Dry powders of WKS13 were first prepared by spray drying, with cyclodextrin used as stabiliser excipient. Two-fluid nozzle (TFN) was used to produce particles below 5 µm for lung deposition (C-TFN formulation) and ultrasonic nozzle (USN) was used to produce particles above 10 µm for nasal deposition (C-USN formulation). Gel electrophoresis and size exclusion chromatography studies showed that the structural integrity of mAb was successfully preserved with no sign of aggregation after spray drying. To achieve dual targeting property, C-TFN and C-USN were mixed at various ratios. The aerosolisation property of the mixed formulations dispersed from a nasal powder device was examined using a Next Generation Impactor (NGI) coupled with a glass expansion chamber. When the ratio of C-TFN in the mixed formulation increased, the fraction of particles deposited in the lung increased proportionally while the fraction of particles deposited in the nasal cavity decreased correspondingly. A customisable aerosol deposition profile could therefore be achieved by manipulating the mixing ratio between C-TFN and C-USN. Dual administration of C-TFN and C-USN powders to the lung and nasal cavity of hamsters, respectively, was effective in offering prophylactic protection against SARS-CoV-2 Delta variant. Viral loads in both the lung tissues and nasal wash were significantly reduced, and the efficacy was comparable to systemic administration of unformulated WKS13. Overall, dual targeting powder formulation of neutralising mAb is a promising approach for prophylaxis of respiratory viral infections. The ease and non-invasive administration of dual targeting nasal powder may facilitate the widespread distribution of neutralising mAb during the early stage of unpredictable outbreaks.

Predominance of inhalation route in short-range transmission of respiratory viruses: Investigation based on computational fluid dynamics.

During the Coronavirus disease 2019 pandemic, short-range virus transmission has been observed to have a higher risk of causing infection than long-range virus transmission. However, the roles played by the inhalation and large droplet routes cannot be distinguished in practice. A recent analytical study revealed the predominance of short-range inhalation over the large droplet spray route as causes of respiratory infections. In the current study, short-range exposure was analyzed via computational fluid dynamics (CFD) simulations using a discrete phase model. Detailed facial membranes, including eyes, nostrils, and a mouth, were considered. In CFD simulations, there is no need for a spherical approximation of the human head for estimating deposition nor the "anisokinetic aerosol sampling" approximation for estimating inhalation in the analytical model. We considered two scenarios (with two spheres [Scenario 1] and two human manikins [Scenario 2]), source-target distances of 0.2 to 2 m, and droplet diameters of 3 to 1,500 µm. The overall CFD exposure results agree well with data previously obtained from a simple analytical model. The CFD results confirm the predominance of the short-range inhalation route beyond 0.2 m for expiratory droplets smaller than 50 µm during talking and coughing. A critical droplet size of 87.5 µm was found to differentiate droplet behaviors. The number of droplets deposited on the target head exceeded those exposed to facial membranes, which implies a risk of exposure through the immediate surface route over a short range. Electronic Supplementary Material ESM: the Supplementary Materials are available in the online version of this article at 10.1007/s12273-022-0968-y.

Antiviral Potential of Coconut (Cocos nucifera L.) Oil and COVID-19

Background: COVID-19 caused by the novel SARS Coronavirus-2 (SARS-CoV-2) is causing serious problems in the global public health sphere. In the absence of a powerful antiviral treatment, the exploration of plant-based products with antiviral potential has gained interest. Scope and Approach: This commentary presents the prospects of utilizing coconut oil directly or its derivatives such as monolaurin in treating COVID-19 with a special emphasis on their biochemical characteristics features. The potential pitfalls therein and way forward are also highlighted. Key findings and conclusions: There are enough research-backed evidences to demonstrate the antiviral capabilities of coconut oil and monolaurin. The possibility of developing a medium-chain fatty acidbased nasal spray as a prophylactic or therapeutic is also discussed. Nevertheless, the potential impediments in devising suitable therapeutic models to treat SARS-CoV-2, are presented.Copyright © 2021 Bentham Science Publishers.

Contactless Fog based Handwash Kit for COVID Safety

Recent days have changed tremendously, and rules are strictly being deployed to maintain social distancing, avoid crowding and frequent hand washing. Frequent washing of hands using our domestic water by a mass crowd result in water wastage which is a huge loss for our society. A better solution to sanitize the hands with reduced water wastage is attempted in this study. With technological advancements in engineering, several solutions and cope-up methods are being given to combat the spread of COVID-19 in this pandemic era. As an attempt, this study develops a Fog based Contactless Handwash kit which uses the Mis Spray method to sanitize the hands. The mist consists of water vapour and herbal sanitizer which is skin-friendly to humans. This kit is suggested to be deployed in public places to avoid the spreading of the virus since it is in a complete contactless manner. It is developed with an Atmega based microcontroller, NodeMCu,ultrasonic sensor and mist spray module economically. The outcomes of the developed handwash kit serve to optimally favour the preventing behaviour in this pandemic time. This study gives way for further research studies on the automatic sanitizing methods to combat the spread of the virus and its variants. © 2022 IEEE.

Lipid based nanocarriers: Production techniques, concepts, and commercialization aspect

Over the past decade, compared to all other macromolecules lipid-based nanocarriers have proven to be an excellent carrier and delivery system for various pharmaceutical drugs of poor bioavailability. In addition to that, they exhibit exceptional qualities such as minimal toxicity, economical scale-up production, great biocompatibility, and high drug loading efficiency. In this study, we have discussed the various types of lipid nanoparticles, such as liposomes, nanostructured lipid carriers, solid lipid nanoparticles, and lipid polymer hybrid nanoparticles. We have also conferred in detail, the composition, shape and size, methods of preparation, advantages, and certain limitations associated with these lipid-based nanocarriers. Additionally, we have exclusively accounted for several examples of lipid-based nanomedicines that have either been approved and commercialized or are under the different phases of clinical trials. The current review overall focuses on the up-to-date research that has recently been published in view of developing lipid-based nanocarriers for various biological applications, including gene therapy, breast cancer therapy, and vaccine development.Copyright © 2022

Reduced ACE2 and TMPRSS2 immunopositive bronchial cells in asthmatics after inhaled allergen challenge

Rationale: The incidence of SARS-CoV-2 infection and the impact of corticosteroid treatment in patients with symptomatic airway disease has been a concern. We examined airway expression of SARS-CoV-2 receptors following allergen challenge and steroid intervention in asthmatic patients. Method(s): From steroid-naive mild allergic asthmatic (AA n=23) we collected endobronchial biopsies pre and 24hr post allergen inhalation challenge (AIC). In a subset of AA with allergic rhinitis (AR n=8) we collected inferior nasal turbinate biopsies pre and 24hr post-nasal allergen challenges (NAC) after placebo treatment or after 21 days of 22 mg BID triamcinolone nasal spray. FEV1 and PNIF expressed as % fall from baseline quantified the early (ER, 0-2h) and late (LR, 3-7h) airway responses post challenge. Epithelium and laminae propria were immunostained for ACE2 and TMPRSS2 and expressed as # cells/mm2. Result(s): AIC reduced FEV1 (31% ER, 19% LR) and the number of bronchial cells immunopositive for ACE2, TMPRSS2 and double positive for ACE2/TMPRSS2 (P=0.0002, P=0.04, P=0.02, respectively). The PNIF reduction by NAC (69% ER, 49% LR) was attenuated by triamcinolone (31% ER, 18% LR), but without changes in ACE2 or TMPRSS2 in nasal tissue after NAC or steroid treatment (all P>0.05). In the nasal tissue, significantly fewer cells expressed ACE2 compared to bronchi (P=0.007). Conclusion(s): ACE2 and TMPRSS2 expression in bronchial tissue is reduced in the T2 microenvironment post allergen challenge, however it is unknown if this protects lower airways from SARS-CoV-2 infection. Low expression of ACE2 and TMPRSS2 in nasal tissue made it difficult to determine the effects of NAC or steroid.

Effects of Usnic Acid to Prevent Infections by Creating a Protective Barrier in an In Vitro Study.

Nasal sprays are medical devices useful for preventing infection and the subsequent spread of airborne pathogens. The effectiveness of these devices depends on the activity of chosen compounds which can create a physical barrier against viral uptake as well as incorporate different substances with antiviral activity. Among antiviral compounds, UA, a dibenzofuran derived from lichens, has the mechanical ability to modify its structure by creating a branch capable of forming a protective barrier. The mechanical ability of UA to protect cells from virus infection was investigated by analyzing the branching capacity of UA, and then the protection mechanism in an in vitro model was also studied. As expected, UA at 37 °C was able to create a barrier confirming its ramification property. At the same time, UA was able to block the infection of Vero E6 and HNEpC cells by interfering with a biological interaction between cells and viruses as revealed also by the UA quantification. Therefore, UA can block virus activity through a mechanical barrier effect without altering the physiological nasal homeostasis. The findings of this research could be of great relevance in view of the growing alarm regarding the spread of airborne viral diseases.

An Enhanced Dissolving Cyclosporin-A Inhalable Powder Efficiently Reduces SARS-CoV-2 Infection In Vitro.

This work illustrates the development of a dry inhalation powder of cyclosporine-A for the prevention of rejection after lung transplantation and for the treatment of COVID-19. The influence of excipients on the spray-dried powder's critical quality attributes was explored. The best-performing powder in terms of dissolution time and respirability was obtained starting from a concentration of ethanol of 45% (v/v) in the feedstock solution and 20% (w/w) of mannitol. This powder showed a faster dissolution profile (Weibull dissolution time of 59.5 min) than the poorly soluble raw material (169.0 min). The powder exhibited a fine particle fraction of 66.5% and an MMAD of 2.97 µm. The inhalable powder, when tested on A549 and THP-1, did not show cytotoxic effects up to a concentration of 10 µg/mL. Furthermore, the CsA inhalation powder showed efficiency in reducing IL-6 when tested on A549/THP-1 co-culture. A reduction in the replication of SARS-CoV-2 on Vero E6 cells was observed when the CsA powder was tested adopting the post-infection or simultaneous treatment. This formulation could represent a therapeutic strategy for the prevention of lung rejection, but is also a viable approach for the inhibition of SARS-CoV-2 replication and the COVID-19 pulmonary inflammatory process.