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1.
J Clin Lab Anal ; : e24725, 2022 Oct 17.
Article in English | MEDLINE | ID: covidwho-2075024

ABSTRACT

It is well known that people's health is seriously threatened by various pathogens (such as Mycobacterium tuberculosis, Treponema pallidum, Novel coronavirus, HIV, Mucor, etc.), which leads to heavy socioeconomic burdens. Therefore, early and accurate pathogen diagnosis is essential for timely and effective therapies. Up to now, diagnosing human contagious diseases at molecule and nano levels is remarkably difficult owing to insufficient valid probes when it comes to determining the biological markers of pathogens. Aptamers are a set of high-specificity and high-sensitivity plastic oligonucleotides screened in vitro via the selective expansion of ligands by exponential enrichment (SELEX). With the advent of aptamer-based technologies, their merits have aroused mounting academic interest. In recent years, as new detection and treatment tools, nucleic acid aptamers have been extensively utilized in the field of biomedicine, such as pathogen detection, new drug development, clinical diagnosis, nanotechnology, etc. However, the traditional SELEX method is cumbersome and has a long screening cycle, and it takes several months to screen out aptamers with high specificity. With the persistent development of SELEX-based aptamer screening technologies, the application scenarios of aptamers have become more and more extensive. The present research briefly reviews the research progress of nucleic acid aptamers in the field of biomedicine, especially in the diagnosis of contagious diseases.

2.
Int J Mol Sci ; 23(20)2022 Oct 18.
Article in English | MEDLINE | ID: covidwho-2071518

ABSTRACT

The regular reappearance of coronavirus (CoV) outbreaks over the past 20 years has caused significant health consequences and financial burdens worldwide. The most recent and still ongoing novel CoV pandemic, caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) has brought a range of devastating consequences. Due to the exceptionally fast development of vaccines, the mortality rate of the virus has been curbed to a significant extent. However, the limitations of vaccination efficiency and applicability, coupled with the still high infection rate, emphasise the urgent need for discovering safe and effective antivirals against SARS-CoV-2 by suppressing its replication or attenuating its virulence. Non-structural protein 1 (nsp1), a unique viral and conserved leader protein, is a crucial virulence factor for causing host mRNA degradation, suppressing interferon (IFN) expression and host antiviral signalling pathways. In view of the essential role of nsp1 in the CoV life cycle, it is regarded as an exploitable target for antiviral drug discovery. Here, we report a variety of fragment hits against the N-terminal domain of SARS-CoV-2 nsp1 identified by fragment-based screening via X-ray crystallography. We also determined the structure of nsp1 at atomic resolution (0.99 Å). Binding affinities of hits against nsp1 and potential stabilisation were determined by orthogonal biophysical assays such as microscale thermophoresis and thermal shift assays. We identified two ligand-binding sites on nsp1, one deep and one shallow pocket, which are not conserved between the three medically relevant SARS, SARS-CoV-2 and MERS coronaviruses. Our study provides an excellent starting point for the development of more potent nsp1-targeting inhibitors and functional studies on SARS-CoV-2 nsp1.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Viral Nonstructural Proteins/metabolism , Ligands , X-Rays , Binding Sites , Antiviral Agents/pharmacology , Interferons , Virulence Factors
3.
Journal of Saudi Chemical Society ; 26(5), 2022.
Article in English | Web of Science | ID: covidwho-2069403

ABSTRACT

Synthesis and structural characterization of nano crystallites of bis-violurate-based manganese(II) and copper(II) chelates is the subject of the present study. Analytical data and mass spectra as well as thermal analysis determined the molecular formulas of the present metal chelates. Spectroscopic and magnetic measurements assigned the structural formula of the present violurate metal complexes. The spectroscopic and magnetic investigations along with structural analysis results indicated the square planar geometry of both the Mn(II) and Cu(II) complexes. The structural analysis of the synthesized metal complexes was achieved by processing the PXRD data using specialized software Expo 2014. Spectrophotometeric and viscosity measurements showed that violuric acid and its Mn(II) and Cu(II) complexes successfully bind to DNA with intrinsic binding constants Kb from 38.2 x 105 to 26.4 x 106 M-1. The antiviral activity study displayed that the inhibitory concentrations (IC50) of SARS-CoV-2 by violuric acid and its Mn(II) and Cu(II) complexes are 84.01, 39.58 and 44.86 lM respectively. Molecular docking calculations were performed on the SARS-CoV-2 virus protein and the computed binding energy values are -0.8, -3.860 -5.187 and -4.790, kcal/mol for the native ligand, violuric acid and its Mn(II) and Cu(II) complexes respectively. Insights into the relationship between structures of the current compounds and their degree of reactivity are discussed.(c) 2022 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

4.
Journal of Biotech Research ; 13:177-188, 2022.
Article in English | ProQuest Central | ID: covidwho-2033805

ABSTRACT

The 3C protease is distinguished from most proteases due to the presence of cysteine nucleophile that plays an essential role in viral replication. This peculiar structure encompassed with its role in viral replication has promoted 3C protease as an interesting target for therapeutic agents in the treatment of diseases caused by human rhinovirus (HRV). However, the molecular mechanisms surrounding the chirality of inhibitors of HRV 3C protease remain unresolved. Herein using in silico techniques such molecular dynamic simulation and binding free estimations via molecular mechanics poisson-boltzmann surface area (MM/PBSA), we present a comprehensive molecular dynamics study of the comparison of two potent inhibitors, SG85 and rupintrivir, complexed with HRV3C protease. The binding free energy studies revealed a higher binding affinity for SG85 of 58.853 kcal/mol than that for rupintrivir of 54.0873 kcal/mol and this was found to be in correlation with the experimental data. The energy decomposition analysis showed that residues Leu 127, Thr 142, Ser 144, Gly 145, Tyr 146, Cys 147, His 161, Val 162, Gly 163, Gly 164, Asn 165, and Phe 170 largely contributed to the binding of SG85, whereas His 40, Leu 127, and Gly 163 impacted the binding of rupintrivir. The results further showed that His 40, Glu 71, Leu 127, Cys 147, Gly 163, and Gyl 164 were crucial residues that played a key role in ligand-enzyme binding, and amongst these crucial residues, His 40, Glu 71, and Cys 147 appeared to be conserved in the active site of HRV-3C protease when bound by both inhibitors. These findings provided a comprehensive understanding of the dynamics and structural features and would serve as guidance in the design and development of potent novel inhibitors of HRV.

5.
SSRN; 2022.
Preprint in English | SSRN | ID: ppcovidwho-343203

ABSTRACT

We report the synthesis of five new Cu(I) acylthiourea complexes (C1-C5) bearing the general formula [Cu(L-R)Cl(PPh3)2] [L = monodentate acylthiourea ligand, R = C6H5 (L1), C6H4CH3(o) (L2), C6H4OCH2CH3(p) (L3), C10H7 (L4) or C6H4Cl(p) (L5)]. All the complexes were characterized by analytical and spectroscopic tools. The complexes (C1-C5) exhibited a distorted tetrahedral geometry as inferred from the single crystal X-ray diffraction study. The complexes were subjected to interaction with biomolecules (calf thymus (CT) DNA/bovine serum albumin (BSA));the one bearing naphthyl substituent (C4) exhibited the highest binding efficacy. Further, anticancer activity of the complexes was studied exclusively against breast cancer cell lines namely MCF7, T47D and MDA MB 231. Complex C4 was found to be highly cytotoxic on the three cancer cell lines with the IC50 values of 0.75, 0.75 and 0.68 µM, respectively. Conveniently, the complexes displayed 4-fold less toxicity against the normal MCF10a human breast cells. Ability of complex C4 to induce apoptosis was analyzed by acridine orange/ethidium bromide (AO/EB) and Hoechst 33258 staining assays. Furthermore, it was found that complex C4 induced apoptosis via reactive oxygen species (ROS)-mediated mitochondrial signaling pathway. Confocal fluorescence images of the cells subjected to lyso and mitotracker staining assays revealed that complex C4 was primarily localized on the mitochondria. Western blot results also confirmed the apoptosis induced by complex C4 in the MDA MB 231 cancer cells. The complexes were also screened for their binding ability with SARS-CoV-2 main protease;interestingly, the complexes exhibited higher binding energy than chloroquine, hydroxychloroquine and remdesivir.

6.
Applied Sciences ; 12(16):8361, 2022.
Article in English | ProQuest Central | ID: covidwho-2023103

ABSTRACT

In the current market, there is a growing interest in traditional herbal nutraceuticals. Therefore, herbal formulations have re-emerged as products with sought-after nutraceutical and disease-preventing properties. The health-promoting effects of herbal bioactives are attributed to the active phytoconstituents of these plants. Thus, the aim of the present study was to evaluate the putative nutraceutical effectiveness of the preparations of ten herbs (chamomile, purple coneflower, lemon verbena, pennyroyal, spearmint, oregano, marjoram, headed savory, sea buckthorn, and St. John’s wort) by combining in silico techniques and LC-MS/MS analysis. The binding potential of the selected phenolic compounds, according to literature and web databases, was investigated by using molecular target prediction tools. Aldose reductase (AR), an enzyme of polyol pathway which is related to hyperglycemic-induced pathologies, emerged as the most promising molecular target. The molecular docking results showed that rosmarinic acid, caftaric acid, naringenin, and quercetin presented the highest binding affinity. In a further step, the phytochemical profile of the examined infusions, obtained by LC-MS/MS analysis, revealed that the abovementioned compounds were present, mainly in the herbs of the Lamiaceae family, designating headed savory as the herbal infusion with possible significant inhibitory activity against AR.

7.
Analytical Chemistry ; 94(33):11591-11599, 2022.
Article in English | Web of Science | ID: covidwho-2016508

ABSTRACT

The COVID-19 pandemic has led to a global crisis with devastating effects on public healthcare and the economy. Sensitive detection of SARS-CoV-2 is the key to diagnose and control its spread. The spike (S) protein is an abundant viral transmembrane protein and a suitable target protein for the selective recognition of SARS-CoV-2. Here, we report that with bovine serum albumin prescreening, a specific phage peptide targeting SARS-CoV-2 S1 protein was biopanned with the pIII phage display library. The identified phage #2 expressing the to the target with a dissociation constant of 3.45 +/- 0.58 nM. Furthermore, the identified peptide shows good specificity with a binding site at the N-terminal domain of the S1 subunit through a hydrogen bond network and hydrophobic interaction, supported by molecular docking. Then, a sandwiched phage-based enzyme-linked chemiluminescence immunoassay (ELCLIA) was established by using phage #2 as a bifunctional probe capable of SARS-CoV-2 S1 antigen recognition and signal amplification. After optimizing the conditions, the proposed phage ELCLIA exhibited good sensitivity, and as low as 78 pg/mL SARS-CoV-2 S1 could be detected. This method can be applied to detect as low as 60 transducing units (TU)/mL SARS-CoV-2 pseudovirus in 50% saliva. Therefore, specific phage peptides have good prospects as powerful biological recognition probes for immunoassay detection and biomedical applications.

8.
Journal of Chemistry ; 2022, 2022.
Article in English | ProQuest Central | ID: covidwho-2001948

ABSTRACT

Two novel metal complexes, that is, Ni (StmAn)2(4) and Cu (StmAn)2(5), were synthesized from unsymmetrical Schiff base ligand StmAn (3). The ligand was prepared by refluxing streptomycin (2) and aniline (1). They were characterized by elemental microanalysis, conductivity measurements, and spectroscopic techniques such as 1H NMR, FT-IR, ESI-mass, and electronic absorption spectral study. Interestingly, the study revealed metal coordination through azomethine nitrogen and N-atom of NH-CH3 of N-methyl-L-glucosamine unit of streptomycin. The electronic absorption spectral study supported an octahedral geometry for complex 4 and a tetrahedral geometry for complex 5. Particle size calculation by Scherrer’s formula indicated their nanocrystalline nature. The geometry optimization of the complexes was achieved by running an MM2 job in Gaussian supported Cs-ChemOffice ultra-12.0.1 and ArgusLab 4.0.1 version software. Based on SwissADME predictions, a theoretical drug profile was generated by analyzing absorption, distribution, metabolism, excretion, and toxicity (ADMET) scores of the compounds. They were screened for in vitro antibacterial activity study against four clinical pathogens such as E. coli, S. pneumoniae, P. vulgaris, and S. aureus. Minimum inhibitory concentration (MIC) study demonstrated greater inhibitory potency of complex (4) (0.024 g/L) for S. aureus relative to ligand (3) and complex (5). Studies show that metal complexes are more toxic to bacteria.

9.
Advanced Functional Materials ; 2022.
Article in English | Web of Science | ID: covidwho-1995522

ABSTRACT

With the rapid progress in nanomaterials and biochemistry, there has been an explosion of interest in biomolecule-modified quantum dots (QDs) for biomedical applications. Metal chalcogenide quantum dots (MCQDs), as the most widely studied QDs, have attracted tremendous attention in the biomedical field on account of their unique and excellent optical properties and the ease of biomolecular modifications. Herein, important advances in MCQDs over recent years are reviewed, from materials design to biomedical applications. Especially, this review focuses on the challenges encountered in the applications of MCQDs in biomedical fields and how these problems can be solved by rational design of synthesis methods and modifications, which have opened a universal route to develop the functionalized MCQDs. Moreover, recent processes in bioimaging, biosensing, and cancer therapy based on MCQDs are examined, including the rapid detection and diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This review provides broad insights into MCQDs in the biomedical field and will inspire material researchers to develop MCQDs in the future.

10.
Applied Sciences ; 12(15):7500, 2022.
Article in English | ProQuest Central | ID: covidwho-1993920

ABSTRACT

(1) Background: Essential oil from Vitex negundo is known to have repellent and insecticidal properties toward the Anopheles gambiae and this is linked to its monoterpene and sesquiterpene content. In this work, an effort is made to delineate the constitution of V. negundo essential oil (VNEO) and their interaction with odorant-binding proteins (OBPs) of A. gambiae and hence access its repellent efficiency as cost-effective and safer malaria vector control alternatives. (2) Methods: Anopheles species authentication was performed by genomic DNA analysis and was subjected to behavioral analysis. GC-MS profiling was used to identify individual components of VNEO. Anopheles OBPs were obtained from the RCSB protein data bank and used for docking studies. Determination of ligand efficiency metrics and QSAR studies were performed using Hyper Chem Professional 8.0.3, and molecular dynamics simulations were performed using the Desmond module. (3) Results: GC-MS analysis of VNEO showed 28 compounds (monoterpenes, 80.16%;sesquiterpenes, 7.63%;and unknown constituents, 10.88%). The ligand efficiency metrics of all four ligands against the OBP 7 were within acceptable ranges. β-selinene (−12.2 kcal/mol), β-caryophellene (−9.5 kcal/mol), sulcatone (−10.9 kcal/mol), and α-ylangene (−9.3 kcal/mol) showed the strongest binding affinities for the target proteins. The most stable hydrophobic interactions were observed between β-selinene (Phe111 and Phe120), Sulcatone (Phe54 and Phe120), and α-ylangene (Phe111), while only sulcatone (Tyr49) presented H-bond interactions in the simulated environment. (4) Conclusions: Sulcatone and β-caryophyllene presented the best log p values, 6.45 and 5.20, respectively. These lead phytocompounds can be used in their purest as repellent supplement or as a natural anti-mosquito agent in product formulations.

11.
J Pharm Drug Res ; 3(2): 341-361, 2020.
Article in English | MEDLINE | ID: covidwho-1989782

ABSTRACT

A novel coronavirus designated as SARS-CoV-2 in February 2020 by World Health organization (WHO) was identified as main cause of SARS like pneumonia cases in Wuhan city in Hubei Province of China at the end of 2019. This been recently declared as Global Pandemic by WHO. There is a global emergency to identify potential drugs to treat the SARS-CoV-2. Currently, there is no specific treatment against the new virus. There is a urgency to identifying potential antiviral agents to combat the disease is urgently needed. An effective and quick approach is to test existing antiviral drugs against. Whole genome analysis and alignment carried out using BLASTn, SMART BLAST and WebDSV 2.0 had shown more than 238 ORF's coding for proteins mostly origin from Bat SARS coronavirus and root genomic origin from Archaea. Molecular docking results against protein targets Furin, papain like proteases, RdRp and Spike glycoprotein had shown paritaprevir, ritonavir, entecavir and chloroquine derivatives are the best drugs to inhibit multi targets of coronavirus infection including natural compounds corosolic acid, baicalin and glycyrrhizic acid with minimal inhibitory concentrations. Thus we propose use of paritaprevir, entecavir, ritonavir and chloroquine derivatives as best drug combination along with niacinamide, folic acid and zinc supplements to treat novel coronavirus infection. We also propose use of plant protease inhibitors (PI's) and Anti-IL8, IL-6, IL-2 as future drug models against coronavirus.

12.
Int J Biol Macromol ; 219: 414-427, 2022 Oct 31.
Article in English | MEDLINE | ID: covidwho-1977348

ABSTRACT

Guanine-rich DNA sequences may fold back into non-canonical four-stranded secondary structures termed as G-quadruplexes. The role of G-quadruplexes has already been well established in different diseases like cancer, neurological and viral disorders etc. Also, several small molecules have been reported, which can influence the involvement of G-quadruplexes either through stabilization or destabilization in the cellular environment. Growing statistics have associated G-quadruplex assemblies to a discrete biological process in vivo, including DNA replication, transcription, genomic stability, and epigenetic regulation. DNA G-quadruplex existence in human telomere is well recognized attractive target for anticancer drugs. G-quadruplex-interactive ligands have been known to prevent telomerase access as well as telomere capping. To the best of our understanding, the role of G-quadruplexes in virology, neuropharmacology, cancer progression and its treatment has not been discussed on a single platform till date. This review aims to enhance our knowledge regarding these magical sticky quadruplex structures, which have been quite significantly proved to be the part of many cellular processes along with their established in vivo existence. Understanding regarding stabilizing or destabilizing ligands of these multistranded guanine quadruplex structures might be proved as the facilitator of drug discovery process for many incurable diseases in future.


Subject(s)
Antineoplastic Agents , G-Quadruplexes , Telomerase , Antineoplastic Agents/pharmacology , DNA/chemistry , Epigenesis, Genetic , Guanine/chemistry , Humans , Ligands , Telomerase/chemistry , Telomere/genetics , Telomere/metabolism
13.
Colloidal Nanoparticles for Biomedical Applications XVII 2022 ; 11977, 2022.
Article in English | Scopus | ID: covidwho-1962038

ABSTRACT

Quantum dots were encapsulated in polymeric phospholipid micelles conjugated to multiple ligands of SARS-CoV-2 spike protein to form fluorescent biomimetic nanoparticles for SARS-CoV-2 (COVID-QDs). Phosphatidylethanolaminepolyethylene glycol (PE:PEG) was appended with bis(4-methylphenyl)sulfone to form PE:PEG:bis-sulfone and self-assembled into micelles around CdSe/CdS core/shell quantum dots via thin-film rehydration. The introduction of the bis-sulfone group the surface of the micelle-encapsulated quantum dots provides multiple sites for conjugation to his-tagged SARS-CoV-2 spike protein via a bisalkylation mechanism. Based on the eluted unconjugated fraction, we estimate that an average of seven spike proteins are conjugated per COVID-QD. We treated an in-vitro model system for the neurovascular unit (NVU) with these COVID-QD constructs to investigate the COVID-QDs, and by proxy SARS-CoV-2, may modulate the NVU leading to the COVID-19 associated neuropathophysiology. © 2022 SPIE

14.
Chromatographia ; 85(8): 773-781, 2022.
Article in English | MEDLINE | ID: covidwho-1935823

ABSTRACT

In this paper, each of the two following proteins, the angiotensin-converting enzyme 2 (ACE2) and the Main protease (Main pro) of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) were grafted for the first time on homemade neutravidin poly(GMA-co-EDMA) capillary columns for the research of their ligands. The effect of the column diameter on the quantity of immobilized biotinylated protein was studied. For a capillary length of 40 mm, when its internal diameter varied from 75 to 25 µm, the grafted quantity of ACE2 decreased by 85% (from 1.50 to 0.24 µg). Among all the studied ligands, a particular vigilance has been given for dexamethasone, a widely used molecule today for adult patients hospitalized with SARS-CoV-2. Competition experiments were performed with SARS-CoV-2 Receptor Binding Domain used as reference molecule with the ACE2 affinity column to assess the orthosteric binding site of dexamethasone (Dex) on ACE2. This ligand was then immobilized on Multiwall Carbon Nanotubes (Dex/MWCNT). By comparison of the normalized breakthrough curves measured for Dex and Dex/MWCNT on both the ACE2 and Main pro affinity columns, it was showed for the first time that nanovectorisation of Dex with MWCNT enhanced and stabilized its binding to both ACE2 and Main pro. This last result reinforced the use of Dex and the interest of MWCNT for boosting immune health against COVID 19.

15.
Nanomaterials (Basel) ; 12(13)2022 Jul 04.
Article in English | MEDLINE | ID: covidwho-1934182

ABSTRACT

Here, the controlled formation of platinum nanoparticles (PtNPs) and silver nanoparticles (AgNPs) using amine-functionalized multivalent ligands are reported. The effects of reaction temperature and ligand multivalency on the growth kinetics, size, and shape of PtNPs and AgNPs were systematically studied by performing a stepwise and a one-step process. PtNPs and AgNPs were prepared in the presence of amine ligands using platinum (II) acetylacetonate and silver (I) acetylacetonate, respectively. The effects of ligands and temperature on the formation of PtNPs were studied using a transmission electron microscope (TEM). For the characterization of AgNPs, additionally, ultraviolet-visible (UV-Vis) absorption was employed. The TEM measurements revealed that PtNPs prepared at different temperatures (160-200 °C, in a stepwise process) are monodispersed and of spherical shape regardless of the ligand multivalency or reaction temperature. In the preparation of PtNPs by the one-step process, ligands affect the shape of the PtNPs, which can be explained by the affinity of the ligands. The TEM and UV-Vis absorption studies on the formation of AgNPs with mono-, di-, and trivalent ligands showed narrower size distributions, while increasing the temperature from 80 °C to 120 °C and with a trivalent ligand in a one-step process.

16.
Journal of Chemistry ; 2022, 2022.
Article in English | ProQuest Central | ID: covidwho-1932846

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, has been a global concern. While there have been some vaccines and drugs, the rapid emergence of variants due to mutations has threatened public health. As the de novo drug development process is expensive and time-consuming, repurposing existing antiviral drugs against SARS-CoV-2 is an alternative and promising approach to mitigate the current situation. Several studies have indicated that some natural products exhibit inhibitory activities against SARS-CoV-2. This study is aimed at analyzing the potential of natural alkaloids, using various computational tools, as drug candidates against SARS-CoV-2. The molecular docking analysis predicted that naturally occurring alkaloids can bind with RNA-dependent RNA-polymerase (RdRP). The QSAR analysis was conducted by using the way2drug/PASS online web resource, and the pharmacokinetics and toxicity properties of these alkaloids were predicted using pkCSM, SwissADME, and ProTox-II webserver. Among the different alkaloids studied, neferine and berbamine were repurposed as potential drug candidates based on their binding affinity and interactions with RdRP. Further, molecular dynamics simulation of 90 ns revealed the conformational stability of the neferine-RdRP complex.

17.
Journal of International Dental and Medical Research ; 15(2):899-903, 2022.
Article in English | ProQuest Central | ID: covidwho-1918870
18.
Philippine Journal of Science ; 150(5):925-937, 2021.
Article in English | CAB Abstracts | ID: covidwho-1871666

ABSTRACT

Herbal plants are often used as alternative medicine because they contain active compounds for the treatment of diseases and disorders with minimal side effects, and are easily obtained from the surrounding environment. Some of them have antiviral activity. This study aimed to analyze the potential of phytochemical compounds in the leaf of "pangi" (Pangium edule Reinw) as anti-SARS-CoV-2 using molecular docking study. The drug- and lead-likeness properties of the selected compounds were obtained from the Swiss ADME and admetSAR online server tools. Molecular dynamics (MD) simulation of the selected ligand was carried out to validate the stability of the interaction. The results suggested that pangi leaves contain three compounds with remarkable binding affinities with Mpro (main protease) and RBD (receptor binding domain) were (5.beta.)pregnane-3,20.beta.-diol, 14.alpha.,18.alpha.-[4-methyl-3-oxo-(1-oxa-4-azabutane-1,4-diyl)]-, diacetate (PD), ethyl cholate (EC), and bis(3,5,5-trimethylhexyl) phthalate. Because EC will be metabolized in the body into cholic acid (Cho), this compound was then docked and validated using MD simulation. The compound has the best free binding energy (G) with SARS-CoV-2 (-7.1 kcal/mol with Mpro and -6.0 kcal/mol with RBD). Moreover, the compound is bound strongly to the active cavity of Mpro on Thr24, Thr26, His41, and Cys145 residues. The MM-GBSA calculation showed that the interaction of Cho with Mpro was higher than with RBD. According to the RMSD (root mean square deviation), RMSF (root mean square fluctuation), the radius of gyration (Rg), and intermolecular hydrogen bond (H-bond) analysis obtained from 50 ns MD simulations, Cho formed stable interactions with Mpro and RBD. The finding of this study indicated that Cho showed good anti-SARS-CoV-2 activity. The potential of the compound to inhibit the virus can serve as a starting point in the process of developing COVID-19 therapeutic natural medicine.

19.
Research Journal of Pharmacy and Technology ; 14(9):4913-4919, 2021.
Article in English | ProQuest Central | ID: covidwho-1871598

ABSTRACT

In 2019 severe acute respiratory syndrome (SARS) - associated with coronavirus is a new highly pathogenic human coronaviruses that emerged in china and has quickly spread all over the world. The mortality rate is about 26% globally. This has resulted in an urgent need to identify antiviral drugs that are active against SARS-Covid - 19. Several compounds extracted from natural product and herbs exhibit antiviral activity. In the present study, eight compounds from natural products and five antiviral drugs have selected and docked against SARS-CoV-2. Curcuminoid are chief constituent of turmeric, has been used as a food additive and herbal increment due to its potential medicinal behavior. Curcumin has shown better antiviral effect against dengue, hepatitis C, zika and chikungunya viruses earlier. The molecular docking for exploring the binding abilities between naturally obtained known compounds comparable with Oseltamivir, Remdesivir, hydroxychloroquine, Zanamivir and Ribavirin against SARS-CoV-2, whose results may be used to design potential drug to meet out the need of the hour. The results showed that bismethoxycurcumin, demethoxycurcumin and gedunin have comparable high binding pose energies against SARS-CoV-2. We anticipate that these molecules may lead to the design or discovery of new effective actions for SARS-CoV-2.

20.
Antibiotics ; 11(5):547, 2022.
Article in English | ProQuest Central | ID: covidwho-1870879

ABSTRACT

Magnesium, copper, zinc, iron and selenium complexes of ceftriaxone were prepared in a 1:1 ligand to metal ratio to investigate the ligational character of the antibiotic ceftriaxone drug (CFX). The complexes were found to have coordinated and hydrated water molecules, except for the Se (IV) complex, which had only hydrated water molecules. The modes of chelation were explained depending on IR, 1HNMR and UV–Vis spectroscopies. The electronic absorption spectra and the magnetic moment values indicated that Mg (II), Cu (II), Zn (II), Fe (III) and Se (VI) complexes form a six-coordinate shape with a distorted octahedral geometry. Ceftriaxone has four donation sites through nitrogen from NH2 amino, oxygen from triazine, β-lactam carbonyl and carboxylate with the molecular formulas [Mg(CFX)(H2O)2]·4H2O, [Cu(CFX)(H2O)2]·3H2O, [Fe(CFX)(H2O)(Cl)]·5H2O, [Zn(CFX)(H2O)2]·6H2O and [Se(CFX)(Cl)2]·4H2O and acts as a tetradentate ligand towards the five metal ions. The morphological surface and particle size of ceftriaxone metal complexes were determined using SEM, TEM and X-ray diffraction. The thermal behaviors of the complexes were studied by the TGA(DTG) technique. This study investigated the effect of CFX and CFX metal complexes on oxidative stress and severe tissue injury in the hepatic tissues of male rats. Fifty-six male rats were tested: the first group received normal saline (1 mg/kg), the second group received CFX orally at a dose of 180 mg/kg, and the other treated groups received other CFX metal complexes at the same dose as the CFX-treated group. For antibacterial activity, CFX/Zn complex was highly effective against Streptococcus pneumoniae, while CFX/Se was highly effective against Staphylococcus aureus and Escherichia coli. In conclusion, successive exposure to CFX elevated hepatic reactive oxygen species (ROS) levels and lipid peroxidation final marker (MDA) and decreased antioxidant enzyme levels. CFX metal complex administration prevented liver injury, mainly suppressing excessive ROS generation and enhancing antioxidant defense enzymes and in male rats.

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