ABSTRACT
Reducing the molecule complexity is achieved by reducing the molecule size after enzymatic digestion to produce smaller fragments more amenable to LC separation and tandem mass spectrometry (MS/MS) sequencing. Non-denaturing CEX chromatography, size-exclusion chromatogra- phy (SEC), hydrophobic interaction chromatography (HIC), and protein A modes can be easily coupled to reversed-phase LC (RPLC) because of the high aqueous conditions, enabling the versatile 4D-LC-MS systems with the use of alternative modes to 1D CEX, such as SEC or Protein A (6,7). [...]the nanopar-ticle size and free drug concentration are determined at the particle Level, whereas the encapsulated drug and lipids forming the layer are commonly characterized at the molecuar level after denaturing the lipid nanoparticle (LNP) via a surfactant. [...]MDLC-MS setups present a formidable opportunity to unify the characterization of drug delivery systems at the molecular and particle evels, which would enable their high throughput analysis.
ABSTRACT
Background/aims: SARS-CoV-2 is responsible of respiratory failure and also causes a massive release of inflammatory mediators such as IL-6, IL-1, CRP etc. This hyperinflammatory condition, often indicated as Cytokine Release Syndrome (CRS), could led to life-threatening events. The clinical course resembles septic shock and the elevated values of inflammatory mediators are associated with a higher viral load and reduced survival. The use of techniques aiming to contrast the surge of inflammatory mediators has been advocated in the treatment of this condition. Method(s): Four patients were retrospectively admitted in Intensive Care Unit with respiratory failure caused by SARS-CoV-2 infection. Two patients were treated with Tocilizumab (TCZ) alone, the others received TCZ in association with hemoadsorption (HA) treatment. The HA procedure was performed with CytoSorb responsible of removing hydrophobic molecules with a molecular weight of up to approximately 60 kDa including cytokines and other inflammatory mediators involved in CRS. Each procedure lasts 24 hours. Blood values of IL-6, C-reactive protein (CRP) and other biochemical variables were measured in two patients who received Tocilizumab (TCZ) alone and in other two in whom it was associated with hemoadsorption (TCZ- HA). All variables were measured before, during and after the treatment. The aim of the study is to assess the variations of IL-6 in patients with SARS-CoV-2 infection treated with TCZ alone or in association with hemoadsorption (HA). Result(s): All patients full-filled the criteria of severe SARS-CoV-2 infection. In all patients the administration of TCZ was followed by an increasing in IL-6 values. Its values remained elevated in patients given TCZ but sharply decreased in the following days in those treated also with HA. The percentage variations of IL-6 from the baseline between the two groups was +344% and +89% in the two patients treated with TCZ alone and - 56% and -15% in TCZ-HA group. Both TCZ and TCZ-HA were well tolerated. Conclusion(s): The increase of the IL-6 can be ascribed to its displacement from cellular and soluble receptors, whereas its decrease is likely due to the scavenging effect exerted by the HA. Although the association TCZ- HA could be valuable in the treatment of the Cytokine Release Storm (CRS) associated with SARS-CoV-2, the HA could be more effective as it neutralizes a wider panel of inflammatory mediators. More experience is needed to identify the best candidate for TCZ or TCZ-HA.
ABSTRACT
The transmission of viruses is largely dependent on contact with contaminated virus-laden communal surfaces. While frequent surface disinfection and antiviral coating techniques are put forth by researchers as a plan of action to tackle transmission in dire situations like the Covid-19 pandemic caused by SARS-CoV-2 virus, these procedures are often laborious, time-consuming, cost-intensive, and toxic. Hence, surface topography-mediated antiviral surfaces have been gaining more attention in recent times. Although bioinspired hydrophobic antibacterial nanopatterned surfaces mimicking the natural sources is a very prevalent and successful strategy, the antiviral prospect of these surfaces is yet to be explored. Few recent studies have explored the potential of nanopatterned antiviral surfaces. In this review, we highlighted surface properties that have an impact on virus attachment and persistence, particularly focusing and emphasizing on the prospect of the nanotextured surface with enhanced properties to be used as antiviral surface. In addition, recent developments in surface nanopatterning techniques depending on the nano-scaled dimensions have been discussed. The impacts of environments and surface topology on virus inactivation have also been reviewed.
ABSTRACT
Background: The outbreak of the COVID-19 pandemic caused by the SARS-CoV-2 has triggered intense scientific research into the possible therapeutic strategies that can combat the ravaging disease. One of such strategies is the inhibition of an important enzyme that affects an important physiological process of the virus. The enzyme, Guanine-N7 Methyltransferase is responsible for the capping of the SARS-CoV-2 mRNA to conceal it from the host's cellular defense. The aim of the study: This study aims at computationally identifying the potential natural inhibitors of the SARS-CoV-2 Guanine-N7 methyltransferase binding at the active site (Pocket 41). Material(s) and Method(s): A library of small molecules was obtained from edible African plants and was molecularly docked against the SARS-CoV-2 Guanine-N7 methyltransferase (QHD43415_13. pdb) using the Pyrx software. Sinefungin, an approved antiviral drug had a binding score of -7.6 kcal/ mol with the target was chosen as a standard. Using the molecular descriptors of the compounds, virtual screening for oral availability was performed using the Pubchem and SWISSADME web tools. The online servers pkCSM and Molinspiration were used for further screening for the pharmacokinetic properties and bioactivity respectively. The molecular dynamic simulation and analyses of the Apo and Holo proteins were performed using the GROMACS software on the Galaxy webserver. Result(s): With a total RMSD of 77.78, average RMSD of 3.704, total regional (active site) RMSF of 30.61, average regional RMSF of 1.91, gyration of 6.9986, and B factor of 696.14, Crinamidine showed the greatest distortion of the target. Conclusion(s): All the lead compounds performed better than the standard while Crinamidine is predicted to show the greatest inhibitory activity. Further tests are required to further investigate the inhibitory activities of the lead compounds.Copyright © 2022 Belgorod State National Research University. All right reserved.
ABSTRACT
Study objective. It has been shown that human common viruses are new target genes for host cell dioxin receptor transcriptional (AhR-ARNT) complex initially proven to up-regulate mammalian genes containing dioxin-response elements (DRE) in the promoters [doi:10.1016/j.ijid.2012.05.265]. Initially, transactivation of HIV-1 and HBV by 2,3,7,8-tetrachlodibenzop- dioxin (TCDD) at low nanomolar range was demonstrated [doi:10.3109/00498259309057034]. Noteworthy, transactivation of human cytomegalovirus (CMV) was shown with 0.3 ppt dioxin, i.e. lower than its current background level in the general population (~3.0 ppt). Recently, reactivation of CMV infection was found to influence worse clinical outcome following SARS-CoV-2 infection (doi: 10.1186/s12979-020- 00185-x). Other findings showed that CMV and herpes simplex virus 1 (HSV-1) reactivation were observed in immunocompetent patients with COVID-19 acute respiratory distress syndrome (ARDS) (doi.org/10.1186/s13054-020-03252-3). Addressing occurrence of Herpesviridae reactivation in severe COVID-19 patients, and still unspecified real triggers of CMV and HSV-1 reactivations, we tested TCDD, which current body burden (DBB) ranges from 20 pg/g (TEQ in fat) in general population to 100 pg/g in older people. Methods. In Silico quantitation of active DRE in promoters of viral genes. Virus DNA hybridization assay. Clinical and epidemiological analyses. Results and Discussion. In this study, a computational search for DRE in CMV and HSV-1 genes was performed by SITECON, a tool recognizing potentially active transcriptional factor binding sites. In silico analysis revealed in regulatory region of CMV IE genes from 5 to 10 DRE, and from 6 to 8 DRE in regulatory region of HSV-1 IE genes.We established that a low picomolar TCDD can trigger up-regulation of CMV and HSV-1 genes via AhR:Arnt transcription factor in macrophage(doi.org/10.1016/ j.ijid.2012.05.265) and glial human cell lines (doi.org/10.1016/j. jalz.2016.06.1268), respectively. In fact, viral reactivation may be triggered in COVID-19 ARDS patients by higher pulmonary TCDD concentrations, because "lipid storm" within lungs of severe COVID-19 patients has been recently reported (doi.org/ 10.1101/2020.12.04.20242115). TCDD is known as the most potent xenobiotic, which bioaccumulates and has estimation half-life in humans of up to 10 yr. Due to hydrophobic character (Log P octanol/water: 7.05), TCDD partitions into inflammatory lipids in lung tissue thus augmenting its local concentration. Population-based epidemiological data on SARS-CoV-2 first wave of pandemic revealed high level of CMV seropositivity and cumulative mortality rate 4.5 times in Lombardi region of Italy, where after Seveso industrial accident TCDD plasma level in pre-exposed subjects is 15 times the level in rest of Italy (doi. org/10.3389/fpubh.2020.620416). Also, Arctic Native (AN) peoples consume dioxin-contaminated fat in seafood and have TCDD DBB, i.e. 7 times that in general population. To the point of this paper, their COVID-19 mortality is 2.2 times of that among non-AN Alaskans (doi: 10.15585/mmwr.mm6949a3). Conclusion(s): TCDD in the picomolar range may trigger CMV expression in lung cells and commit virus to the lytic cycle, which can be applied to reactivation of Herpesviridae infection in immunocompetent patients with COVID-19 ARDS syndrome.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.
ABSTRACT
Tuberculosis (TB) is second only to COVID-19 as the most lethal cause of death from a single infectious agent. Current primary methods for diagnosing TB infection present significant limitations such as lengthy time-to-result for phenotypic tests, the need for a priori knowledge of Mycobacterium tuberculosis (Mtb) resistance mutations, and prohibitive cost for molecular tests. Here, we present fluorogenic solvatochomic trehalose probes that enables rapid detection of live Mtb. In particular, we designed a 4-N,N-dimethylamino-1,8-naphtha-limide- conjugated trehalose (DMN-Tre) probe that undergoes >700-fold increase in fluorescence intensity when transitioned from aqueous to hydrophobic environments. This enhancement occurs upon metabolic conversion of DMN-Tre to trehalose monomycolate and incorporation into the mycomembrane of Actinobacteria. DMN-Tre labeling enabled the rapid, no-wash visualization of mycobacterial and corynebacterial species without nonspecific labeling of Gram-positive or Gram-negative bacteria.DMN-Tre labeling was detected within minutes and was inhibited by heat killing of mycobacteria. Furthermore, DMN-Tre labeling was reduced by treatment with TB drugs, unlike the clinically used auramine stain. Lastly, DMN-Tre labeled Mtb in TB-positive human sputum samples comparably to auramine staining, suggesting that this operationally simple method may be deployable for TB diagnosis.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.
ABSTRACT
Background: SARS-CoV-2 evolution has contributed to successive waves of infections and severely compromised the efficacy of available SARS-CoV-2 monoclonal antibodies. Decaying vaccine-induced immunity, vaccine hesitancy, and limited vaccine protection in older and immunocompromised populations further compromises vaccine efficacy at the population level. Early antiviral treatments, including intravenous remdesivir (RDV), reduce hospitalization and severe disease due to COVID-19. An orally bioavailable RDV analog could facilitate earlier widespread administration to non-hospitalized COVID-19 patients. Method(s): We synthesized monoalkyl glyceryl ether phosphodiesters of GS-441524 (RVn), lysophospholipid analogs which allow for oral bioavailability and stability in plasma. We evaluated the in vivo efficacy of our lead compound, 1-O-octadecyl-2-O-benzyl-sn-glyceryl-3-phospho-RVn (V2043), in an oral treatment model of murine SARS-CoV-2 infection. We then synthesized numerous phospholipid analogs of RVn and determined which modifications enhanced in vitro antiviral activity and selectivity. The most effective compounds against SARS-CoV-2 were then evaluated for antiviral activity against other RNA viruses. Result(s): Oral treatment of SARS-CoV-2 infected BALB/c mice with V2043 (60 mg/kg once daily for 5 days, starting 12 hrs after infection) reduced lung viral load by more than 100-fold versus vehicle at day 2 and to below the LOD at day 5. V2043 inhibited previous and contemporary SARS-CoV-2 Variants of concern to a similar degree, as measured by the half maximal effective concentration (EC50) in a human lung epithelial cell line (Calu-3). Evaluation of multiple RVn analogs with hydrophobic esters at the sn-2 of glycerol revealed that in vitro antiviral activity was improved by the introduction of a 3-fluoro-4-methoxysubstituted benzyl or a 3-or 4-cyano-substituted benzyl. These compounds showed a 2-to 6-fold improvement in antiviral activity compared to analogs having an unsubstituted benzyl, such as V2043, and were more active than RDV. These compounds also showed enhanced antiviral activity against multiple contemporary and emerging RNA viruses. Conclusion(s): Collectively, our data support the development of RVn phospholipid prodrugs as oral antiviral agents for prevention and treatment of SARS-CoV-2 infections and as preparation for future outbreaks of pandemic RNA viruses.
ABSTRACT
The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is causing coronavirus disease 2019 (COVID-19) pandemic. Ancient Chinese herbal formulas are effective for diseases caused by viral infection, and their effects on COVID-19 are currently being examined. To directly evaluate the role of Chinese herbs in inhibiting replication of SARS-CoV-2, we investigated how the phytochemicals from Chinese herbs interact with the viral RNA-dependent RNA polymerase (RdRP). Total 1025 compounds were screened, and then 181compounds were selected for molecular docking analysis. Four phytochemicals licorice glycoside E, diisooctyl phthalate, (-)-medicocarpin, and glycyroside showed good binding affinity with RdRp. The best complex licorice glycoside E/RdRp forms 3 hydrogen bonds, 4 hydrophobic interactions, 1 pair of Pi-cation/stacking, and 4 salt bridges. Furthermore, docking complexes licorice glycoside E/RdRp and diisooctyl phthalate/RdRp were optimized by molecular dynamics simulation to obtain the stable conformation. These studies indicate that they are promising as antivirals against SARS-CoV-2.Copyright © The Author(s) 2022.
ABSTRACT
Background: Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has given rise to COVID-19 pandemic, which has become a wreaking havoc worldwide. Therefore, there is an urgent need to find out novel drugs to combat SARS-CoV-2 in-fection. In this backdrop, the present study aimed to assess potent bioactive compounds from different fungi as potential inhibitors of SARS-CoV-2 main protease (Mpro) using an in-silico analysis. Method(s): High-Resolution Liquid Chromatography Mass Spectrometry analysis (HR-LCMS) was used for the bioactive profiling of ethanolic crude extract of Dictyophora indusiata, Geastrum tri-plex and Cyathus stercoreus. Of which, only bergenin (D. indusiata), quercitrin (G. triplex) and di-hydroartemisinin (C. stercoreus) were selected based on their medicinal uses, binding score and the active site covered. The 6LU7, a protein crystallographic structure of SARS-CoV-2 Mpro, was docked with bergenin, quercitrin and dihydroartemisinin using Autodock 4.2. Result(s): A total of 118 bioactive compounds were analyzed from the crude extract of used fungi and identified using HR LC/MS analysis. The binding energies obtained were-7.86,-10.29 and-7.20 kcal/mol, respectively, after docking analysis. Bergenin, quercitrin and dihydroartemisinin formed hydrogen bond, electrostatic interactions and hydrophobic interactions with foremost active site amino acids THR190, GLU166, GLN189, GLY143, HIS163, HIS164, CYS145 and PHE140. Conclusion(s): Present investigation suggests that these three compounds may be used as alternative inhibitors against SARS-CoV-2 Mpro. However, further research is necessary to assess in vitro potential of these compounds. To the best of our knowledge, the present investigation reported these three bioactive compounds of fungal origin for the first time.Copyright © 2021 Bentham Science Publishers.
ABSTRACT
The mass casualties caused by the delta variant and the wave of the newer "Omicron" variant of SARS-COV-2 in India have brought about great concern among healthcare officials. The government and healthcare agencies are seeking effective strategies to counter the pandemic. The application of nanotechnology and repurposing of drugs are reported as promising approaches in the management of COVID-19 disease. It has also immensely boomed the search for productive, re-liable, cost-effective, and bio-assimilable alternative solutions. Since ancient times, the traditional-ly employed Ayurvedic bhasmas have been used for diverse infectious diseases, which are now employed as nanomedicine that could be applied for managing COVID-19-related health anomalies. Like currently engineered metal nanoparticles (NPs), the bhasma nanoparticles (BNPs) are also packed with unique physicochemical properties, including multi-elemental nanocrystalline compo-sition, size, shape, dissolution, surface charge, hydrophobicity, and multi-pathway regulatory as well as modulatory effects. Because of these conformational and configurational-based physico-chemical advantages, Bhasma NPs may have promising potential to manage the COVID-19 pandemic and reduce the incidence of pneumonia-like common lung infections in children as well as age-related inflammatory diseases via immunomodulatory, anti-inflammatory, antiviral, and adju-vant-related properties.Copyright © 2023 Bentham Science Publishers.
ABSTRACT
New and fascinating physical, chemical and biological phenomena arise in ultra-small materials, such as graphene. Graphene is a single layer formed only for carbon atoms, super-strong, 200 times stronger than steel and as much as 6 times lighter. It also has a high elasticity and densi-ty. Furthermore, it seems to be impermeable to almost everything, but allows the passage of water and air. Due to its versatility, modern and urgent applications arise every day, one of the most ne-cessary, currently, is the control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the novel coronavirus disease (COVID-19), which has dimensions around 100 nm and has caused a worldwide public health emergency. Different ways to prevent coronavirus contagion has proposed and one of them is the use of masks. Here, we investigated some properties of graphene that can help combat COVID-19. A scale appropriate for comparison shows that the spatial dimension of a virus is much larger than the graphene sheet, making it a great candidate for manufacturing face masks, filters and respirators. We also make use of first-principles calculations, based on the density functional theory (DFT), to investigate the interaction between graphene and a water molecule. We observed that the water molecule undergoes a repul-sion force when it is very close to the graphene sheet. The hydrophobicity of graphene can be important to prevent the face mask that doesn't get wet when you breathe with it.Copyright © 2021 Bentham Science Publishers.
ABSTRACT
A contribution of Lung Surfactant (LS) inactivation to COVID-19-related ARDS (cvARDS) has been argued, but not been clearly demonstrated to date. In the present study, we have characterised the extent of lung neutrophil infiltration along with the surface-active properties and protein composition of LS in bronchoalveolar lavages (BALs) collected from 12 cvARDS patients. A control group of 9 subjects without respiratory diseases was also enrolled. BAL cell sorting was performed by flow cytometry. The adsorption of LS at the air-liquid interface was assessed by Surfactant Adsorption Test (SAT), whereas the level of surfactant hydrophobic proteins was measured by Western Blot analysis. Results were normalised by phosphatidylcholine (PC) total amount. Significant increase in neutrophil [61.3(47.5-84.6)% vs 1.6(0.9-4.9)%, p<0.0001] and decrease in macrophage percentages [13.6(6.1-28.9)% vs 90.8(87.1-92-6)%, p<0.0001] of total BAL cells were detected in cvARDS patients. A lower overtime LS adsorption/accumulation at the air-liquid interface was also observed in those patients compared to the control group from 60min onward [14003(10232-19736) vs 24501(16386-28489) RFU, p=0.0471]. Moreover, cvARDS patients under the acute phase showed the lowest surfactant activity at the end of SAT (12191(11588-20159) RFU, p=0.048). An increase in both SP-B and SP-C/PC was also evident in cvARDS BALs. Here, we report for the first time on the reduction of LS surface-active properties during the acute period and even under the recovery phases of cvARDS. This may confirm how LS inactivation may be involved in both early and late consequences of severe cvARDS.
ABSTRACT
The spread and variation of COVID-19 in the world have seriously threatened human health. Therefore the current focus of research is to develop medical and antiepidemic textiles with high filtering efficiency and bacteriostasis and low filtering resistance. Polypropylene PP melt-blown nonwovens are commonly used as raw materials for medical antiepidemic textiles. PP melt-blown nonwovens as the core filter layer of medical textiles were difficult to buy during the outbreak of the epidemic. However the traditional PP melt-blown nonwovens have low antibacterial performance and medical staff are vulnerable to virus infection and microbial damage in the process of use for their single function and certain limitations in protective ability. Therefore in the post-pandemic era PP melt-blown nonwovens should not only be able to meet the rigid demand of the market but also evolve to be high-end and functional in the face of mutating COVID-19 and the possibility of a return at any time. The research combines the PP melt-blown nonwoven with the electrospinning nanofiber membrane to prepare compound nonwoven fabrics with high antibacterial activity. In order to improve the antibacterial property of PP melt-blown nonwovens composite nanofiber membranes were synthesized on PP melt-blown nonwovens by electrospinning technology. Firstly the PP melt-blown nonwoven was used as receiving substrate of electrospinning equipment and nano copper oxide CuO-NPS was used as anti-bacterial material to prepare the PP / PAN / CuO-NPS composite nonwovens with high antibacte-rial performance. On the basis of that effects of the CuO-NPS mass fraction and electrospinning time on the surface morphology fiber diameter distribution chemical constitution filtration performance hydrophobicity and antibacterial property of composite nonwovens were studied. The results show that the bacteriostasis rates of composite nonwovens to gram-negative E. coli and gram-positive S. aureus are both greater than 99. 99% in the range of CuO-NPS mass fraction of 0. 3% - 0. 9% and the spinning time is 1 h. When the spinning time is 1 h as the mass fraction of CuO-NPS increases the fiber diameter of the composite nonwoven increases and its distribution uniformity of diameter and hydrophobic property both decrease. Under the condition of constant mass fraction of CuO-NPS the filtration efficiency of composite nonwovens improves with the extension of the spinning time but the permeability decreases. With the same spinning time the filtration efficiency of composite nonwovens increases with the increase in CuO-NPS mass fraction. In addition in-corporating CuO-NPs into PAN nanofiber membrane does not change the chemical structure of the membrane. We select polyacrylonitrile PAN with good spinning performance as the raw material and CuO-NPs as the antibacterial material to prepare CuO-NPs powder with antibacterial properties to prepare electrostatic spinning solution. The composites of PP melt-blown nonwovens and electrospun PAN / CuO-NPs nanofibrous membrane have been obtained which not only improves the filtration performance of PP melt-blown nonwovens but also endows them with efficient antibacterial property. This paper provides a reference for further studies on the production and application of PP melt-blown nonwovens. (English) [ABSTRACT FROM AUTHOR] 针对聚丙烯( PP)熔喷非织造布抗菌性能不足的问题,本文以 PP 熔喷非织造布为静电纺丝装置的接受基布、 CuO-NPs 为抗菌材料,制备具有高效抗菌性能的聚丙烯 / 聚丙烯腈 / 纳米氧化铜( PP / PAN / CuO-NPs) 复合非织造布。 研究了 CuO-NPs 质量分数 与 静 电 纺 丝 时 间 对 复 合 非 织 造 布 抗 菌 等 性 能 的 影 响。 结 果 表 明:当 纺 丝 时 间 为 1 h、 CuO-NPs 质量分数在 0. 3% ~ 0. 9% 时,复合非织造布对 E. coli 和 S. aureus 的抑菌率均 > 99. 99% 。 纺丝时间为 1 h, 随着 CuO-NPs 质量分数增大,复合非织造布纤维直径增大、直径分布均匀性降低、疏水性能下降。 CuO-NPs 质量分 数不变,随着纺丝时间增加,复合非织造布的过滤效率提升,透气性却下降。 纺丝时间相同,复合非织造布的过滤效 率随着 CuO-NPs 质量分数增大而增大;CuO-NPs 质量分数增大时,复合非织造布的透气性在较短纺丝时间( 0. 5 ~ 1 h)内先下降后提升,在较长纺丝时间(1. 5 ~ 2. 5 h)内显著下降。 此外,CuO-NPs 的加入不会改变 PAN 纳米纤维膜 的化学结构。 静电纺纳米纤维膜与 PP 基布的复合可以制备高效过滤和抑菌的医用防疫纺织品。 (Chinese) [ABSTRACT FROM AUTHOR] Copyright of Journal of Silk is the property of Zhejiang Sci-Tech University Magazines and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
ABSTRACT
Introduction: COVID-19 is an acute respiratory infectious disease caused by the SARS-CoV-2 virus. There is an urgent need to discover antiviral drugs for better performance against new strains of coronaviruses (CoVs) due to the rapid spread of the disease despite scientific advances in vaccine development. This study aimed to evaluate the efficacy of quercetin and its analogues on the COVID-19 Mpro enzyme. Material & Methods: In this descriptive-analytical study, the three-dimensional structures of quercetin analogues (20 compounds), standard drugs (ritonavir and lopinavir), and the COVID-19 Mpro enzyme were obtained from PubChem and PDB databases for bioinformatics study, respectively. Molecular docking studies of the compounds on theMpro were performed using MOE-2014 software. Afterward, the physicochemical properties and biological activity of the compounds were predicted using Swiss ADME, PASS, and Swiss Target Prediction software. Findings: The findings of the present study showed that the most important bonds involved in drug-receptor binding are hydrogen, hydrophobic, and - interaction bonds. The best docking results were obtained for Baicalein, Genistein, Naringenin, and Quercetin compounds with strong binding energy (-12.83 to -13.54 kcal/mol), compared to ritonavir and lopinavir. These compounds have a greater tendency to bind to the catalytic amino acids His41 and Cys145 and other key amino acids of the active site of the COVID-19 Mpro enzyme. Discussion & Conclusion: Based on the results of bioinformatics studies, quercetin analogues had more effective inhibition than standard chemical drugs due to their suitable placement in the active site of the main protease enzyme of COVID-19 and can be good candidates for in vitro and in vivo studies.
ABSTRACT
Personal protective textiles have attracted extensive interest since Corona Virus Disease 2019 has broken out. Moreover, developing eco-friendly, multifunctional waterproof, and breathable surface is of great importance but still faces enormous challenges. Notably, good hydrophobicity and breathability are necessary for protective textiles, especially protective clothing and face masks for healthcare. Herein, the multifunctional composite coatings with good UV-resistant, anti-oxidative, hydrophobic, breathable, and photothermal performance has been rapidly created to meet protective requirements. First, the gallic acid and chitosan polymer was coated onto the cotton fabric surface. Subsequently, the modified silica sol was anchored on the coated cotton fabric surface. The successful fabrication of composite coatings was verified by RGB values obtained from the smartphone and K/S value. The present work is an advance for realizing textile hydrophobicity by utilizing fluorine-free materials, compared with the surface hydrophobicity fabricated with conventional fluorinated materials. The surface free energy has been reduced from 84.2 to27.6 mJ/m2 so that the modified cotton fabric could repel the ethylene glycol, hydrochloric acid, and sodium hydroxide solutions, respectively. Besides, the composite coatings possesses lower adhesion to deionized water. After 70 cycles of the sandpaper abrasion, the fluorine-free hydrophobic coatings still exhibits good hydrophobicity with WCA of 124.6 ± 0.9°, with overcoming the intrinsic drawback of the poor abrasion resistance of hydrophobic surfaces. Briefly, the present work may provide a universal strategy for rapidly creating advanced protective coatings to meet personal healthcare, and a novel method for detecting RGB values of composite coatings by smartphone.
ABSTRACT
Infections caused by enveloped viruses require fusion with cellular membranes for viral genome entry. Viral entry occurs following an interaction of viral and cellular membranes allowing the formation of fusion pores, by which the virus accesses the cytoplasm. Here, we focus on interferon-induced transmembrane protein 3 (IFITM3) and its antiviral activity. IFITM3 is predicted to block or stall viral fusion at an intermediate state, causing viral propagation to fail. After introducing IFITM3, we describe the generalized lipid membrane fusion pathway and how it can be stalled, particularly with respect to IFITM3, and current questions regarding IFITM3's topology, with specific emphasis on IFITM3's amphipathic α-helix (AAH) 59V-68M, which is necessary for the antiviral activity. We report new hydrophobicity and hydrophobic moment calculations for this peptide and a variety of active site peptides from known membrane-remodeling proteins. Finally, we discuss the effects of posttranslational modifications and localization, how IFITM3's AAH may block viral fusion, and possible ramifications of membrane composition.
ABSTRACT
Abundant disposable surgical masks (SMs) remain in the environment and continue to age under urban environmental stressors. This study aimed to investigate the aging characteristics of SMs and the effect of different aged layers of SMs on phenanthrene (PHE), tylosin (TYL), and sulfamethazine (SMT) under two different urban environmental stressors (UV and ozone). The results show that UV exposure causes more severe aging of the SM layers than ozone. The middle layer, made of melt-brown fabric, has displayed the highest degree of aging due to its smaller diameter and mechanical strength. The two-dimensional correlation spectroscopy (2D-COS) analysis reveals the different aging sequences of functional groups and three layers in aged SMs under the two urban environmental stressors. Whether the SMs are aged or not, the adsorptions of three organic pollutants on SMs are positively correlated with the octanol-water partition coefficient. Furthermore, except for the dominant hydrophobic interaction, aged SMs can promote the adsorption of three organic pollutants by accessory interactions (hydrogen bonding and partition), depending on their structures. These findings highlight the environmental effects of new microplastic (MP) sources and coexisting pollutants under the influence of COVID-19, which is helpful in accurately evaluating the biological toxicity of SMs. © 2022 Elsevier B.V.
ABSTRACT
Partitioning and effect of antiviral GC376, a potential SARS-CoV-2 inhibitor, on model lipid membranes was studied using dynamic light scattering (DLS), UV–VIS spectrometry, Excimer fluorescence, Differential scanning calorimetry (DSC) and Small- and Wide-angle X-ray scattering (SAXS/WAXS). Partition coefficient of GC376 between lipid and water phase was found to be low, reaching KP = 46.8 ± 18.2. Results suggest that GC376 partitions into lipid bilayers at the level of lipid head-groups, close to the polar/hydrophobic interface. Changes in structural and thermodynamic properties strongly depend on the GC376/lipid mole ratio. Already at lowest mole ratios GC376 induces increase of lateral pressures, mainly in the interfacial region of the bilayer. Hereby, the pre- and main-transition temperature of the lipid system increases, what is attributed to tighter packing of acyl chains induced by GC376. At GC376/DPPC ≥ 0.03 mol/mol we detected formation of domains with different GC376 content resulting in the lateral phase separation and changes in both, main transition temperature and enthalpy. The observed changes are attributed to the response of the system on the increased lateral stresses induced by partitioning of GC376. Obtained results are discussed in context of liposome-based drug delivery systems for GC376 and in context of indirect mechanism of virus replication inhibition.
ABSTRACT
Objective: Coronavirus disease-19 (COVID-19) is global pandemic which caused by SARS-CoV-2 infection. Mechanism of infection is initiated by attachment between viral glycoprotein with ACE2 receptor in human cells. Furthermore, Indonesia had a massive diversity of plants with a high potency of drugs, such as Pogostemon cablin Benth. In brief, it contained of various volatile compounds with many therapeutic properties. Therefore, this research aimed to identify the ability of volatile compounds from Pogostemon cablin Benth as a potential inhibitor of SARS-CoV-2 spike glycoprotein. Method(s): SMILE notation of 22 volatile compounds of Pogostemon cablin Benth were collected from PubChem and the 3D structure of SARS-CoV-2 glycoprotein (PDB ID: 6VXX) was obtained from PDB database. Simulation of interaction between volatile compound and glycoprotein was conducted by using Pyrx molecular docking. Moreover, the complex of compounds-glycoprotein was depicted by using Chimera and the amino acid residue was analysed by using LigPlot. Selected potential compounds were identified for biological activity prediction, drug-likeness, and toxicity analysis. Result(s): Analysis showed that among those volatile compounds, only caryophyllene oxide (-6.3 kcal/mol) naturally bind specific into RBD site as compared to the control. Furthermore, it had comparable hydrogen and hydrophobic interactions with glycoprotein. Further analysis showed it has strong potential biological function for antiviral with low toxicity. Conclusion(s): Caryophyllene oxide is considered as promising candidate compounds that inhibited viral infection through SARS-CoV-2 glycoprotein. Copyright © 2023, Innovare Academics Sciences Pvt. Ltd. All rights reserved.
ABSTRACT
SARS-CoV-2 virus has caused pandemic disease since the end of 2019. Virus transmission occurs through droplet and infects the host's respiratory tract rapidly. Viral propagation occurs through translation process of genome +ssRNA, then it being replicated forming some new body parts of virus and assemblied into virions that ready to infect. During the replication process, the translated viral genome in the form of polyprotein will be cut into smaller components by proteases, which one is 3CLpro. The presence of the 3CLpro receptor is used in drug development through in-silico molecular docking process to minimize failures before laboratory test. The antivirus compounds that used to inhibit the 3CLpro receptor are from gletang plant (Tridax procumbens Linn.). This study aim is to determine the value of binding affinity, the interaction between compounds and receptor, and the effect of drug components. The research was conducted by in-silico through the molecular docking process of 3CLpro receptor and antivirus compounds of gletang (Tridax procumbens Linn.), including betulinic acid, kaempferol and lignan. The results showed that the binding affinity of betulinic acid was -6.6 kcal/mol, kaempferol was -5.6 kcal/ mol and lignan was -5.4 kcal/mol. The interaction form of compounds and receptor was hydrogen bond, electrostatic, hydrophobic, and van der Waals. Compared to baicalein compound as a positive control with the value of binding affinity was -6.7 kcal/mol and its interaction with 3CLpro receptor, showed betulinic acid, kaempferol and lignan have smaller ability but they have the potential to inhibit the 3CLpro receptor. Copyright © 2022 Phcogj.Com.