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1.
Journal of the Academy of Consultation-Liaison Psychiatry ; 63:S68, 2022.
Article in English | EMBASE | ID: covidwho-1966674

ABSTRACT

Background: Due to COVID pandemic, there have been increased needs for ECMO circuits to support patients with respiratory failure1. Unfortunately, due to pharmacokinetics alteration of commonly used sedative and psychotropic medications by the ECMO circuits2,new sedation approaches to manage delirium and agitation is required. We present a case of COVID pneumonia patient on ECMO support, whose delirium symptoms were managed with a novel psychopharmacotherapy protocol. Case: Mr. M is a 57-year-old male patient with past medical history of obesity, hypertension, admitted to Stanford Hospital due to COVID pneumonia, complicated by respiratory failure, required to be on Veno-Venous ECMO support with bridge to transplant. He had significant hyperactive delirium with Richmond Agitation-Sedation Scale (RASS) score of +3 and ICDSC score of 7 for most of the days, despite heavy conventional pharmacological sedation. We observe the same problems with most patients placed on the ECMO system, leading to an investigation and development of a new protocol. Discussion: Patient on ECMO support requires adequate sedation to prevent clinical deterioration that can result from hyperactive delirium (ie., chugging, blood clots or decannulation)2. Nevertheless, ECMO circuit’s significant alterations of drug pharmacokinetics, such as increased volume of distribution and sequestration of lipophilic and protein bound medications, with no clear guidelines on managing sedation/delirium in patients with ECMO support at this time2, we conducted an extensive literature search and developed a novel protocol. This new sedation approach includes alpha-2 agonists, opioids, barbiturates and calcium channel modulators with the lowest lipophilicity and protein binding potential of each medication in its class4,5,thus overcoming the challenges introduced by ECMO circuits. The new protocol allowed the patient to participate in lung transplant work-up, physical therapy, and eventually facilitated receiving bilateral lung transplantation. Conclusion/Implications: ECMO is a life saving device that can help patient with cardiac-respiratory failure, and its use has been increasing in clinical practice. However, there needs to be an improvement in successful sedation/delirium management to minimize adverse events, and optimize the success of this lifesaving technologies. References: 1. Cho HJ, et al. ECMO use in COVID-19: lessons from past respiratory virus outbreaks-a narrative review. Crit Care. 2020 Jun 6;24(1):301 2. deBacker J, et al. Sedation Practice in Extracorporeal Membrane Oxygenation-Treated Patients with Acute Respiratory Distress Syndrome: A Retrospective Study. ASAIO J. 2018 Jul/Aug;64(4):544-551 3. Lemaitre F, et al. Propofol, midazolam, vancomycin and cyclosporine therapeutic drug monitoring in extracorporeal membrane oxygenation circuits primed with whole human blood. Crit Care. 2015;19(1):40 4. Hansch C, et al. Hydrophobicity and central nervous system agents: on the principle of minimal hydrophobicity in drug design. J Pharm Sci. 1987 Sep;76(9):663-87 5. Bockbrader HN, et al. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet. 2010 Oct;49(10):661-9

2.
Drug Delivery Letters ; 12(1):54-61, 2022.
Article in English | EMBASE | ID: covidwho-1957135

ABSTRACT

Background: The COVID-19 pandemic emerged at the end of 2019 in China and spread rapidly all over the world. Scientists strive to find virus-specific antivirals against COVID-19 disease. This study aimed to assess bioactive coumarinolignans (Aquillochin, Grewin) as potential SARS-CoV-2 main protease (SARS-CoV-2 Mpro) inhibitors using a molecular docking study. Methods: The detailed interactions between coumarinolignans and SARS-CoV-2 Mpro were determined as hydrophobic bonds, hydrogen bonds, electronic bonds, inhibition activity, ligand efficiency, bonding type, and distance using Autodock 4.2 software. SARS-CoV-2 Mpro was docked with Aquillochin and Grewin, and the docking results were analyzed by Autodock 4.2 and Biovia Discovery Studio 4.5. Nelfinavir and Lopinavir were used as standards for comparison. Results: The binding energies of the SARS-CoV-2 Mpro-coumarinolignan’s complexes were identified from the molecular docking of SARS-CoV-2 Mpro. Aquillochin and Grewin were found to be-7.5 and-8.4 kcal/mol, respectively. The binding sites of the coumarinolignans to SARS-CoV-2 Mpro were identified with the main interactions being π-alkyl, alkyl, π-cation, π-π T-Shaped, and hydrogen bonding. Furthermore, SwissADME web tools were used to evaluate ADMET properties and pharmacokinetic parameters of Aquillochin and Grewin. The results of ADMET and pharmacokinetic results of the Aquillochin and Grewin showed that these coumarinolignans were consonant with the many accepted rules and the criteria of drug-likeness. Conclusion: Aquillochin and Grewin obey Lipinski’s rule of five. According to the results obtained from molecular docking studies and ADMET predictions, Aquillochin and Grewin have shown weak efficacy as drug candidates against COVID-19 disease.

3.
1st International Conference on Technologies for Smart Green Connected Society 2021, ICTSGS 2021 ; 107:19031-19039, 2022.
Article in English | Scopus | ID: covidwho-1950350

ABSTRACT

Obesity is a metabolic condition that accounts for life-threatening disorders like cancer, cardiovascular diseases, and type-2 diabetes. There are several anti-obesity drugs currently available on the market, but many of them show poor bioavailability due to low water solubility. Several attempts have been made by researchers to improve the solubility of orally administered drugs, but many of them did not work properly. Herein, we introduced a block copolymer micelle consisting of poly (lactic acid)-co-poly (ethylene glycol) to improve the solubility of the anti-obesity drug "Fenofibrate”. The block copolymer was synthesized using the polycondensation method, while the micelle was formed when water was added dropwise to the copolymer. Finally, laser light scattering and DLS analysis were used to confirm the micelle formation. The size of the micelle increased from 158 nm to 249 nm after the fenofibrate drug loading inside the hydrophobic core. The polymer PLA-co-PEG can be used as a carrier for orally administered fenofibrate drugs in the future for better water solubility and efficiency. © The Electrochemical Society

4.
Pakistan Journal of Medical and Health Sciences ; 16(6):395-400, 2022.
Article in English | EMBASE | ID: covidwho-1939797

ABSTRACT

Because it has been well defined, bovine serum albumin (BSA) is highly suited to pharmacological effects, biotransformation, and bio-distribution of medicines initial research. Drug–protein interactions in the blood stream are known to have a significant impact on drug distribution, free concentration, and metabolism. Coronavirus disease 2019 (COVID-19) has spread globally as a severe pandemic. It is a serious threat to healthcare systems, economies, and is devastating to some populations, such as the elderly and those with comorbidities. Unfortunately, there is still no effective cure for COVID-19, especially the critically ill patients. The link between the mortality risk of patients hospitalized for COVID-19 and the function of blood albumin levels has been investigated. Because of albumin biological significance, the study goal conducted to apply spectroscopic methods to explore and comparing the kinetic and thermodynamic aspects of ceftriaxone's interaction with BSA, albumin isolated from healthy and covid-19 plasma. A pooled plasma from healthy and hospitalized covid-19 individuals (Karbala Province / Iraq) was used to purify albumin using HPLC technique. UV-vis spectrophotometric measurements of albumin-ceftriaxone complex formation recorded at different pH (7, 7.2, 7.4, 7.6 & 7.8) in phosphate buffer solution, and at six different temperatures (298, 301, 304, 307, 310 & 313) K. The equilibrium constant and the thermodynamic parameter such as ΔG, ΔH and ΔS were calculated. The drug-albumin (BSA, healthy and Covid-19 albumin) complexes are stable in 60 to 300 minutes, as evidenced by the steady absorbance studies. The reaction is from the first false order for drug-albumin (BSA, healthy and covid-19 plasma) complexes. Our finding suggesting the reaction is from the first false order. In the case of plasma albumin from individuals infected with - Covid-19, the values of (R2) are closer together. This is because the medication dominates the formation of a more stable complex with albumin. The stoichiometric ratio (coordination number) of complex between ceftriaxone and albumin at 298 k and pH=7.4 is 1:1. The Gibbs free energy for albumin-ceftriaxone is negative, indicating that the reaction is spontaneous. The positive enthalpy of contact indicates that the process is endothermic, requiring energy input. Positive enthalpy and entropy change also refer to the hydrophobic association and electrostatic contact that occurs between albumin molecules and ceftriaxone. It is worth noting that the complex formed between bovine albumin and the medication has less absorbency at pH = 7.4. That is, the complex is more stable, and it prefers natural helical shapes. Additionally, as the pH value shifts away from physiological (> 7.4 <), the intensity of complex absorption increases.

5.
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927796

ABSTRACT

Rationale The recent emergence of a novel coronavirus, SARS-CoV-2, has led to the global pandemic of the severe disease COVID-19 in humans. While efforts to quickly identify effective antiviral therapies have focused largely on repurposing existing drugs, the current standard of care, remdesivir, remains the only authorized antiviral intervention of COVID-19 and provides only modest clinical benefits. Thus, new antivirals targeting SARS-CoV-2 are urgently needed. Methods Artificial intelligence algorithm MediKanren was used to query FDA-approved and late-stage drug compounds for potential interactions with SARS-CoV-2 proteins, coronaviruses, and host cell networks for possible antiviral activity. From this, 157 compounds were further tested in an antiviral screen against live SARS-CoV-2 for reduction in viral growth. Select compounds were further assessed for synergistic activity with remdesivir. Both in vitro and cell free systems identified tocopherol succinate compounds that inhibited the RNA-dependent RNA polymerase (RdRp). Validation of antiviral and synergistic activity was performed in primary human airway epithelial cell cultures against multiple SARS-CoV-2 variants.Results Here we show that water-soluble derivatives of α-tocopherol have potent antiviral activity and synergize with remdesivir as inhibitors of the SARS-CoV-2 (RdRp). Through an artificial-intelligence-driven in silico screen and in vitro viral inhibition assay, we identified D-α-tocopherol polyethylene glycol succinate (TPGS) as an effective antiviral against SARS-CoV-2 and β-coronaviruses more broadly that also displays strong synergy with remdesivir. We subsequently determined that TPGS and other water-soluble derivatives of α- tocopherol inhibit the transcriptional activity of purified SARS-CoV-2 RdRp and identified affinity binding sites for these compounds within a conserved, hydrophobic interface between SARS-CoV- 2 nonstructural protein 7 and nonstructural protein 8 that is functionally implicated in the assembly of the SARS-CoV-2 RdRp. Conclusion In summary, solubilizing modifications to α-tocopherol allow it to interact with the SARS-CoV-2 RdRp, making it an effective antiviral molecule alone and even more so in combination with remdesivir. These findings are significant given that many tocopherol derivatives, including TPGS, are considered safe for humans, orally bioavailable, and dramatically enhance the activity of the only approved antiviral for SARS-CoV-2 infection.

6.
Korean Chemical Engineering Research ; 60(2):282-288, 2022.
Article in Korean | Web of Science | ID: covidwho-1870102

ABSTRACT

Facial masks have become indispensable in daily life to prevent infection and spread through respiratory droplets in the era of the corona pandemic. To understand how effective two different types of masks (i.e., KF-94 mask and dental mask) are in blocking respiratory droplets, i) we preferentially analyze wettability characteristics (e.g., contact angle and contact angle hysteresis) of filters consisting of each mask, and ii) subsequently observe the dynamic behaviors of microdroplets impacting at high velocities on the filter surfaces. Different wetting properties (i.e., hydrophobicity and hydrophilicity) are found to exhibit depending on the constituent materials and pore sizes of each filter. In addition, the pneumatic conditions for stably and uniformly dispensing microdroplets with a certain volume and impacting behaviors associated with the impacting velocity and filter type change are systematically explored. Three distinctive dynamics constituting the masks and droplet impact velocity. The present experimental results not only provide very useful

7.
Embase; 2021.
Preprint in English | EMBASE | ID: ppcovidwho-337395

ABSTRACT

SARS-CoV-2 infection is initiated by binding of the receptor-binding domain (RBD) of its spike glycoprotein to the peptidase domain (PD) of angiotensin-converting enzyme 2 (ACE2) receptors in host cells. Recently detected Omicron variant of SARS-CoV-2 (B.1.1.529) is heavily mutated on RBD. Currently, the most common Omicron variants are the original BA.1 Omicron strain and the BA.2 variant, which became more prevalent since it first appeared. To investigate how these mutations affect RBD-PD interactions, we performed all-atom molecular dynamics simulations of the BA.1 and BA.2 RBD-PD in the presence of full-length glycans, explicit water and ions. Simulations revealed that RBDs of BA.1 and BA.2 variants exhibit a more dispersed interaction network and make an increased number of salt bridges and hydrophobic interactions with PD compared to wild-type RBD. Although BA.1 and BA.2 differ in two residues at the RBD-ACE2 interface, no major difference in RBD-PD interactions and binding strengths were observed between these variants. Using the conformations sampled in each trajectory, the Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) method estimated ~34% and ~51% stronger binding free energies for BA.1 and BA.2 RBD, respectively, than wild-type RBD, which may result in higher binding efficiency of the Omicron variant to infect host cells.

8.
Nano Today ; 43: 101445, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1851860

ABSTRACT

Aluminum oxyhydroxide (AlOOH) adjuvants are widely used in human vaccines. However, the interaction mechanisms at the material-bio interface, and further understandings on physicochemical property-dependent modulation of the immune responses still remain uncertain. Herein, a library of AlOOH nanorods with well-defined aspect ratios is designed to explore the mechanisms of adjuvanticity. The aspect ratios of AlOOH nanorods were demonstrated to be intrinsically modulated by the hydroxide supersaturation level during crystal growth, leading to the differences in surface free energy (SFE). As a result, higher aspect ratio AlOOH nanoadjuvants with lower SFE exhibited more hydrophobic surface, resulting in more membrane depolarization, cellular uptake and dendritic cell (DC) activation. By using hepatitis B surface antigen (HBsAg) virus-like particles (VLPs) or SARS-CoV-2 spike protein receptor-binding domain (RBD) as model antigens, AlOOH nanorods with higher aspect ratio were determined to elicit more potent humoral immune responses, which could be attributed to the enhanced DC activation and the efficient antigen trafficking to the draining lymph nodes. Our findings highlight the critical role of aspect ratio of AlOOH nanorods in modulating adjuvanticity, and further provide a design strategy for engineered nanoadjuvants for prophylactic vaccines.

9.
Virology ; 570: 1-8, 2022 05.
Article in English | MEDLINE | ID: covidwho-1839383

ABSTRACT

Enveloped viruses such as Coronaviridae (CoV) enter the host cell by fusing the viral envelope directly with the plasma membrane (PM) or with the membrane of the endosome. Replication of the CoV genome takes place in membrane compartments formed by rearrangement of the endoplasmic reticulum (ER) membrane network. Budding of these viruses occurs from the ER-Golgi intermediate compartment (ERGIC). The relationship between proteins and various membranes is crucial for the replication cycle of CoVs. The role of transmembrane domains (TMDs) and pre-transmembrane domains (pre-TMD) of viral proteins in this process is gaining more recognition. Here we present a thorough analysis of physico-chemical parameters, such as accessible surface area (ASA), average hydrophobicity (Hav), and contribution of specific amino acids in TMDs and pre-TMDs of single-span membrane proteins of human viruses. We focus on unique properties of these elements in CoV and postulate their role in adaptation to diverse host membranes and regulation of retention of membrane proteins during replication.


Subject(s)
Coronaviridae , Cell Membrane/metabolism , Endoplasmic Reticulum/metabolism , Humans , Membrane Proteins/genetics , Membrane Proteins/metabolism , Protein Domains , Viral Proteins/metabolism
10.
Biomedical and Pharmacology Journal ; 15(1):433-444, 2022.
Article in English | EMBASE | ID: covidwho-1822621

ABSTRACT

The coronavirus outbreak and its mutant variants have harmed the health of the human populace and imperiled the world economy. Several studies are initiated across the globe using clinical biomarkers from hematological, immunological, and biochemical experiments. In addition, analysis of protein interfaces provides an understanding of the functioning of the coronavirus target proteins. This study examines the interfaces of spike glycoproteins in terms of large (vdW dominant) and small (vdW subdominant) interfaces. We also calculated Gibbs free energy (?G), residue propensity and hot-spot prediction for these interfaces. Dataset consisting of 115 (large interface with vdW dominant) and 18 (small interface with vdW subdominant) were obtained from PDB. Results show that 86% of the total interfaces were vdW dominant, while the rest, 14%, were sub-dominant in vdW energy. Interestingly, on average, we found the Gibbs free energy (?G) of large and small interfaces to be -21 and -30 kcal/mol respectively. We also found the interfaces of large and small to be highly pronounced with polar residues followed by hydrophobic residues in case of large interfaces and charged residues in case of small interfaces. We found and report methionine residues to be absent at the small interfaces having subdominant vdW energy. We also observed the majority of the interfaces to be rich in hotspot residues. Thus, the information on heteromeric interactions of glycoproteins may help develop new and productive therapeutic drugs.

11.
Pathogens ; 11(4)2022 Apr 12.
Article in English | MEDLINE | ID: covidwho-1785870

ABSTRACT

Feline coronavirus (FCoV) infections present as one of two forms: a mild or symptom-less enteric infection (FEC) and a fatal systemic disease termed feline infectious peritonitis (FIP). The lack of epidemiology of FCoV in central China and the reason why different symptoms are caused by viruses of the same serotype have motivated this investigation. Clinical data of 81 suspected FIP cases, 116 diarrhea cases and 174 healthy cases were collected from veterinary hospitals using body cavity effusion or fecal samples. Risk factors, sequence comparison and phylogenetic studies were performed. The results indicated that FIPV was distinguished from FECV in the average hydrophobicity of amino acids among the cleavage sites of furin, as well as the mutation sites 23,531 and 23,537. FIPV included a higher minimal R-X-X-R recognition motif of furin (41.94%) than did FECV (9.1%). The serotype of FCoV was insignificantly correlated with FIP, and the clade 1 and clade 2 strains that appeared were unique to central China. Thus, it is hypothesized that this, along with the latent variables of an antigenic epitope at positions 1058 and 1060, as well as mutations at the S1/S2 sites, are important factors affecting FCoV transmission and pathogenicity.

12.
Indian Journal of Clinical Biochemistry ; 36(SUPPL 1):S12, 2021.
Article in English | EMBASE | ID: covidwho-1767670

ABSTRACT

Computation approach to drug discovery has Cbecome an important tool for understanding the mechanism of the interaction between the protein and inhibhitor complex. Different computational approach can be utilised for studying drug-delivery, stability of the protein and also in designing of vaccines. In the presentation, a brief discussion regarding the different tools used for studying the stability of a protein, drug delivery and designing vaccines will be discussed by giving examples from SARS-Cov2 as a model protein system. The effect of hydrophobic group, electron withdrawing effect, hydrogen bonding effect of the substituents present in the inhibitor effects the potency of the antagonist. Further, the stability of a protein, RNA can be analysed by studying the network analysis of the conformation evolution of the biomolecule. Immunoinformatic tools are also found to be important for designing vaccines as they help to identify B-cell, Tcell epitopes.

13.
ACS Sustainable Chemistry and Engineering ; 2021.
Article in English | Scopus | ID: covidwho-1764128

ABSTRACT

Fogging on transparent surfaces such as goggles causes a series of hazards to users. To fabricate antifogging and low-haze transparent renewable polymer materials, intrinsic hydrophilicity with high water adsorption capability of thermoplastic starch (TPS) had been adopted. Strikingly, when benzoic acid (BA) was blended with thermoplastic starch (TPS-BA), the haze of TPS-BA was only 7.8% when it suffered the cold and warm method of antifogging measurement with 87% transmittance. Simultaneously, TPS-BA achieved an 18 mm inhibition zone for Staphylococcus aureus. To reveal the antifogging mechanism of TPS-BA films, the surficial and interior structure features were evaluated by three-dimensional optical scanner, scanning electron microscopy (SEM), contact angle testing, small-angle X-ray scattering (SAXS), X-ray diffraction (XRD), temperature-dependent Fourier transform infrared (FTIR), dynamic mechanical analysis (DMA), and so on. The incorporation of BA resulted in the roughness (Rq), water contact angle (WCA), and crystallinity of the TPS-BA film decreasing from 6.5 to 0.68 μm, 65.1 to 39.9°, and 13.6 to 6.3%, respectively. The amorphous matrix and smooth surface reduced the scattered light, allowing the TPS-BA film to achieve low haze performance and high transmittance. Importantly, the diversified and weakened hydrogen bonds formed among starch, BA, and glycerol could inhibit the formation of starch crystalline regions and allowed hydroxyl groups to quickly bond with water. Thus, when TPS-BA is placed in a high-humidity surrounding, an "expressway"is constructed for water molecules diffusing into the TPS-BA matrix. This novel low-haze, antifogging, sustainable, and facilely fabricated TPS with antibacterial properties is a promising candidate in disposable medical goggles to fight against COVID-19. © 2021 American Chemical Society. All rights reserved.

14.
Pertanika Journal of Tropical Agricultural Science ; 45(1):235-244, 2022.
Article in English | CAB Abstracts | ID: covidwho-1727536

ABSTRACT

Cat's whiskers or the 'misai kucing' is an herbal plant native to the Southeast Asian region. The polyphenol enriched leaf extract contains numerous medicinal properties of major pharmaceutical interest. In this study, selected cat's whiskers polyphenols were screened computationally to predict the minimum binding affinities with severe acute respiratory syndrome coronavirus (SARS-CoV) molecular targets. Molecular docking analysis showed that the caffeic acid derivatives and polymethoxylated flavonoids from cat's whiskers bound stably to the binding pocket regions of SARS-CoV molecular targets at - 4.2 to - 7.1 kcal/mol. Furthermore, these cat's whiskers polyphenol-bound SARS-CoV complexes were held fairly strongly by hydrophobic interactions, hydrogen bonds, and electrostatic interactions at various extents.

15.
Mathematical Problems in Engineering ; 2022, 2022.
Article in English | ProQuest Central | ID: covidwho-1701014

ABSTRACT

This work presents the splitting dynamics of low-viscous fingers inside the single bifurcating channel through the surface wettability of daughter branches. The propagation of low-viscous fingers inside branching microchannels have importance in many applications, such as microfluidics, biofluid mechanics (pulmonary airway reopening), and biochemical testing. Several numerical simulations are performed where a water finger propagates inside the silicon oil-filled bifurcating channel, and at the bifurcating tip, it splits into two fingers and these fingers propagate into the separate daughter branches. It is noticed that the behaviour of finger splitting at the bifurcating tip depends upon numerous parameters such as surface wettability, capillary number, viscosity ratio, and surface tension. This study aims to trigger the behaviour of finger splitting through the surface wettability of daughter branches θ1,θ2. Therefore, a series of numerical simulations are performed by considering four different surface wettability configurations of daughter branches, i.e., θ1,θ2∈78°,78°;78°,118°;78°,150°;150°,150°. According to the results obtained from numerical simulations, finger splitting may be categorized into three types based on splitting ratio λ, i.e., symmetrical splitting, nonsymmetrical splitting, and reversal (no) splitting. It is noticed that the surface wettability of both daughter branches is either hydrophilic 78°,78° or superhydrophobic 150°,150°, providing symmetrical splitting. The surface wettability of one of the daughter branches is hydrophilic and another is hydrophobic 78°,118°, providing nonsymmetrical splitting. The surface wettability of one of the daughter branches is hydrophilic and another is superhydrophobic 78°,150°, providing reversal splitting. The findings of this investigation may be incorporated in the fields of biochemical testing and occulted pulmonary airways reopening as well as respiratory diseases such as COVID-19.

16.
Journal of the Iranian Chemical Society ; 19(3):839-846, 2022.
Article in English | ProQuest Central | ID: covidwho-1694223

ABSTRACT

Ferrocene and its derivatives are vital class of organometallic compounds having extensive biological activities. Six novel ferrocene-based thiosemicarbazones have been synthesized through the condensation reaction of acetyl ferrocene with differently substituted thiosemicarbazide. Furthermore, we used state-of-the-art computational docking approach to explore the theoretical aspects for possible antiviral potential of our synthesized compounds. All the six compounds were docked with Mpro protein of SARS-CoV-2, which is very crucial protein for viral replication. Among the six derivatives, compounds 2 and 4 showed higher binding affinities with binding energy of − 6.7 and − 6.9 kcal/mol, respectively. The visualization of intermolecular interactions between synthesized derivatives and Mpro protein illustrated that each of compounds 2 and 4 forms two hydrogen bonds accompanied by important hydrophobic interactions. The comparison of binding affinities with some recently approved drugs like remdesivir, chloroquine and hydroxychloroquine molecules are also made. The calculated binding energies of remdesivir, chloroquine and hydroxychloroquine molecules with Mpro of COVID-19 was found to be − 7.00, − 5.20 and − 5.60 kcal/mol, respectively. The binding energy of compound 4 (− 6.9 kcal/mol) was almost equal to the remdesivir and greater than the binding energies of chloroquine and hydroxychloroquine. It is expected from the current investigation that our synthesized ferrocene-based thiosemicarbazones might have potential for drug against SARS-CoV-2.

17.
Journal of Materials Research and Technology ; 2022.
Article in English | ScienceDirect | ID: covidwho-1624782

ABSTRACT

This study evaluated the effect of hexamethyldisiloxane (HMDSO) plasma on the fabrics surface to produce masks. Samples of 400-thread count cotton fabric were used. The fabrics was covered with a layer of HMDSO employing plasma enhanced chemical vapor deposition. Optical Microscopy, helium ion beam microscopy (HIM) and atomic force microscopy (AFM) were used for topographic analysis. Fourier transformed infrared spectroscopy technique was used to analyze the chemical modifications on surface. The level of hydrophobicity was evaluated using contact angle measurements. To evaluate the effect of washing cycle on the plasma coating, a protocol proposed by the World Health Organization was used. All experiments were performed in triplicate. For the statistical analysis, the Mann-Whitney, Kruskal-Wallis and Dunn tests were used. AFM showed that, after HMDSO plasma coating, a layer of small granules agglomerated on the original surface of the fabric was visualized. The fabric, which initially had a 0° contact angle value, presented angles of 120o after the plasma coating. It was concluded that the use of cotton fabric coated with HMDSO plasma proved to be adequate for the manufacture of protective masks, since the coating made the surface hydrophobic and this property is maintained even after washing cycles.

18.
European Journal of Integrative Medicine ; 48, 2021.
Article in English | EMBASE | ID: covidwho-1587787

ABSTRACT

Introduction: SARS-CoV-2 infection is a lethal disease caused by a Novel strain of coronaviruses. Although vaccinations of healthy people and meticulous treatment of infected people are the main global health concerns, some plant species have therapeutic effects against viral infections. Matricaria chamomilla is one of the most famous medicinal plants used to manage flu or flu-like symptoms due to its antiviral bioactivity. M. chamomilla belongs to a large group of medicinal herbs used by Persian scholars such as Avicenna and Rhazes to treat respiratory diseases. It has more than 120 chemical constituents, including terpenoids, flavonoids, and some components with potential medicinal activity. In this study, the inhibitory effect of 2 major flavonoid components of M. chamomilla, apigenin and luteolin, was studies for the main protease protein of SARS-CoV-2. Methods: Molecular docking studies were performed using an in-house batch script (DOCKFACE) of Auto Dock 4.2. The 3D structures of the selected flavonoids were retrieved from PubChem, and each ligand was optimized with MM+ then AM1 minimization method using HyperChem 8. The 3D crystal structure of the main protease protein of SARS-CoV-2 (PDB ID: 6LU7) was obtained from the Protein Data Bank (http://www.rcsb.org./pdb). Results: Apigenin and luteolin exhibited good docking scores against 6LU7 receptor, -7.86 and -7.24, respectively, with a combination of hydrogen bonding, van der Waals, and other hydrophobic interactions in the docked complexes. Besides, the estimated inhibition constants, Ki, showed that luteolin exhibited a better inhibitory effect than apigenin. Conclusions: Based on these results, the authors proposed that M. chamomilla can be considered as a valuable resource recommended for preventing SARS-CoV-2 invasion into the human body. Keywords: COVID-19, M. chamomilla, Persian medicine, Molecular Docking, Herbal medicine

19.
Biomedical Signal Processing and Control ; 73, 2022.
Article in English | EMBASE | ID: covidwho-1568534

ABSTRACT

An approach based on fractal scaling analysis to characterize the organization of the SARS-CoV-2 genome sequence was used. The method is based on the detrended fluctuation analysis (DFA) implemented on a sliding window scheme to detect variations of long-range correlations over the genome sequence regions. The nucleotides sequence is mapped in a numerical sequence by using four different assignation rules: amino-keto, purine-pyrimidine, hydrogen-bond and hydrophobicity patterns. The originally reported sequence from Wuhan isolates (Wuhan Hu-1) was considered as a reference to contrast the structure of the 2002–2004 SARS-CoV-1 strain. Long-range correlations, quantified in terms of a scaling exponent, depended on both the mapping rule and the sequence region. Deviations from randomness were attributed to serial correlations or anti-correlations, which can be ascribed to ordered regions of the genome sequence. It was found that the Wuhan Hu-1 sequence was more random than the SARS-CoV-1 sequence, which suggests that the SARS-CoV-2 possesses a more efficient genomic structure for replication and infection. In general, the virus isolated in the early 2020 months showed slight correlation differences with the Wuhan Hu-1 sequence. However, early isolates from India and Italy presented visible differences that led to a more ordered sequence organization. It is apparent that the increased sequence order, particularly in the spike region, endowed some early variants with a more efficient mechanism to spreading, replicating and infecting. Overall, the results showed that the DFA provides a suitable framework to assess long-term correlations hidden in the internal organization of the SARS-CoV-2 genome sequence.

20.
IUBMB Life ; 74(3): 213-220, 2022 03.
Article in English | MEDLINE | ID: covidwho-1516764

ABSTRACT

The global spread of SARS-CoV-2 is fast moving and has caused a worldwide public health crisis. In the present article, we analyzed spike protein sequences of SARS-CoV-2 genomes to assess the impact of mutational diversity. We observed from amino acid usage patterns that spike proteins are associated with a diversity of mutational changes and most important underlying cause of variation of amino acid usage is the changes in hydrophobicity of spike proteins. The changing patterns of hydrophobicity of spike proteins over time and its influence on the receptor binding affinity provides crucial information on the SARS-CoV-2 interaction with human receptor. Our results also show that spike proteins have evolved to prefer more hydrophobic residues over time. The present study provides a comprehensive analysis of molecular sequence data to consider that mutational variants might play a crucial role in modulating the virulence and spread of the virus and has immediate implications for therapeutic strategies.


Subject(s)
SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Angiotensin-Converting Enzyme 2/metabolism , Genome, Viral , Humans , Hydrophobic and Hydrophilic Interactions , Molecular Docking Simulation , Mutation , Spike Glycoprotein, Coronavirus/metabolism
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