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1.
Front Chem ; 10: 948553, 2022.
Article in English | MEDLINE | ID: covidwho-2109731

ABSTRACT

Considering the significant impact of the recent COVID-19 outbreak, development of broad-spectrum antivirals is a high priority goal to prevent future global pandemics. Antiviral development processes generally emphasize targeting a specific protein from a particular virus. However, some antiviral agents developed for specific viral protein targets may exhibit broad spectrum antiviral activity, or at least provide useful lead molecules for broad spectrum drug development. There is significant potential for repurposing a wide range of existing viral protease inhibitors to inhibit the SARS-CoV2 3C-like protease (3CLpro). If effective even as relatively weak inhibitors of 3CLpro, these molecules can provide a diverse and novel set of scaffolds for new drug discovery campaigns. In this study, we compared the sequence- and structure-based similarity of SARS-CoV2 3CLpro with proteases from other viruses, and identified 22 proteases with similar active-site structures. This structural similarity, characterized by secondary-structure topology diagrams, is evolutionarily divergent within taxonomically related viruses, but appears to result from evolutionary convergence of protease enzymes between virus families. Inhibitors of these proteases that are structurally similar to the SARS-CoV2 3CLpro protease were identified and assessed as potential inhibitors of SARS-CoV2 3CLpro protease by virtual docking. Several of these molecules have docking scores that are significantly better than known SARS-CoV2 3CLpro inhibitors, suggesting that these molecules are also potential inhibitors of the SARS-CoV2 3CLpro protease. Some have been previously reported to inhibit SARS-CoV2 3CLpro. The results also suggest that established inhibitors of SARS-CoV2 3CLpro may be considered as potential inhibitors of other viral 3C-like proteases.

2.
Curr Top Med Chem ; 2022 Nov 03.
Article in English | MEDLINE | ID: covidwho-2109532

ABSTRACT

The COVID-19 outbreak and the pandemic situation have hastened the research community to design a novel drug and vaccine against its causative organism, the SARS-CoV-2. The spike glycoprotein present on the surface of this pathogenic organism plays an immense role in viral entry and antigenicity. Hence, it is considered an important drug target in COVID-19 drug design. Several three-dimensional crystal structures of this SARS-CoV-2 spike protein have been identified and deposited in the Protein DataBank during the pandemic period. This accelerated the research in computer-aided drug designing, especially in the field of structure-based drug designing. This review summarizes various structure-based drug design approaches applied to this SARS-CoV-2 spike protein and its findings. Specifically, it is focused on different structure-based approaches such as molecular docking, high-throughput virtual screening, molecular dynamics simulation, drug repurposing, and target-based pharmacophore modelling and screening. These structural approaches have been applied to different ligands and datasets such as FDA-approved drugs, small molecular chemical compounds, chemical libraries, chemical databases, structural analogs, and natural compounds, which resulted in the prediction of spike inhibitors, spike-ACE-2 interface inhibitors, and allosteric inhibitors.

3.
Curr Pharm Des ; 2022 Nov 07.
Article in English | MEDLINE | ID: covidwho-2109516

ABSTRACT

Study background & Objective: After the influenza pandemic (1918), COVID-19 was declared a Vth pandemic by the WHO in 2020. SARS-CoV-2 is an RNA-enveloped single-stranded virus. Based on the structure and life cycle, Protease (3CLpro), rdrp, ACE2, IL-6, and TMPRSS2 are the major targets for drug development against COVID-19. Pre-existing several drugs (FDA-approved) are used to inhibit the above targets in different diseases. In coronavirus treatment, these drugs are also in different clinical trial stages. Remdesivir (rdrp inhibitor) is the only FDA-approved medicine for coronavirus treatment. In the present study, by using the drug repurposing strategy, 70 preexisting clinical or under clinical trial molecules were used in scrutiny for rdrp inhibitor potent molecules in coronavirus treatment being surveyed via docking studies. Molecular simulation studies further confirmed the binding mechanism and stability of the most potent compounds. MATERIAL AND METHODS: Docking studies were performed using the Maestro 12.9 module of Schrodinger software over 70 molecules with rdrp as the target and remdesivir as the standard drug and further confirmed by simulation studies. RESULTS: The docking studies showed that many HIV protease inhibitors demonstrated remarkable binding interactions with the target rdrp. Protease inhibitors such as lopinavir and ritonavir are effective. Along with these, AT-527, ledipasvir, bicalutamide, and cobicistat showed improved docking scores. RMSD and RMSF were further analyzed for potent ledipasvir and ritonavir by simulation studies and were identified as potential candidates for corona disease. CONCLUSION: The drug repurposing approach provides a new avenue in COVID-19 treatment.

4.
Inform Med Unlocked ; 35: 101134, 2022.
Article in English | MEDLINE | ID: covidwho-2105133

ABSTRACT

Background: SARS-CoV-2 initially originated in Wuhan (China) around December 2019, and spread all over the world. Currently, WHO (Word Health Organization) has licensed several vaccines for this viral infection. However, not everyone can be vaccinated. People with underlying health conditions that weaken their immune systems or those with severe allergies to some vaccine components, may not be able to be vaccinated. Moreover, no vaccination is 100% safe, and the emergence of new SARS-CoV-2 mutations may reduce the efficacy of immunizations. Therefore, it is urgent to develop effective drugs to protect people against this virus. Material and method: We performed structure-based virtual screening (SBVS) of a library that was built from ChemDiv and PubChem databases against four SARS-CoV-2 target proteins: S-protein (spike), main protease (MPro), RNA-dependent RNA polymerase, and PLpro. A virtual screening study was performed using PyRx and AutoDock tools. Results: Our results suggest that twenty-five top-ranked drugs with the highest energy binding as the potential inhibitors against four SARS-CoV-2 targets, relative to the reference molecules. Based on the energy binding, we suggest that these compounds could be used to produce effective anti-viral drugs against SARS-CoV-2. Conclusion: The discovery of novel compounds for COVID-19 using computer-aided drug discovery tools requires knowledge of the structure of coronavirus and various target proteins of the virus. These compounds should be further assessed in experimental assays and clinical trials to validate their actual activity against the disease. These findings may contribute to the drug design studies against COVID-19.

5.
Comput Biol Med ; 151(Pt A): 106298, 2022 Nov 11.
Article in English | MEDLINE | ID: covidwho-2104650

ABSTRACT

OBJECTIVES: Recently, it has been reported that cepharanthine (CEP) is highly likely to be an agent against Coronavirus disease 2019 (COVID-19). In the present study, a network pharmacology-based approach combined with RNA-sequencing (RNA-seq), molecular docking, and molecular dynamics (MD) simulation was performed to determine hub targets and potential pharmacological mechanism of CEP against COVID-19. METHODS: Targets of CEP were retrieved from public databases. COVID-19-related targets were acquired from databases and RNA-seq datasets GSE157103 and GSE155249. The potential targets of CEP and COVID-19 were then validated by GSE158050. Hub targets and signaling pathways were acquired through bioinformatics analysis, including protein-protein interaction (PPI) network analysis and enrichment analysis. Subsequently, molecular docking was carried out to predict the combination of CEP with hub targets. Lastly, MD simulation was conducted to further verify the findings. RESULTS: A total of 700 proteins were identified as CEP-COVID-19-related targets. After the validation by GSE158050, 97 validated targets were retained. Enrichment results indicated that CEP acts on COVID-19 through multiple pathways, multiple targets, and overall cooperation. Specifically, PI3K-Akt signaling pathway is the most important pathway. Based on PPI network analysis, 9 central hub genes were obtained (ACE2, STAT1, SRC, PIK3R1, HIF1A, ESR1, ERBB2, CDC42, and BCL2L1). Molecular docking suggested that the combination between CEP and 9 central hub genes is extremely strong. Noteworthy, ACE2, considered the most important gene in CEP against COVID-19, binds to CEP most stably, which was further validated by MD simulation. CONCLUSION: Our study comprehensively illustrated the potential targets and underlying molecular mechanism of CEP against COVID-19, which further provided the theoretical basis for exploring the potential protective mechanism of CEP against COVID-19.

6.
Comput Biol Med ; 151(Pt A): 106288, 2022 Nov 12.
Article in English | MEDLINE | ID: covidwho-2104649

ABSTRACT

SARS-CoV-2 Mpro (Mpro) is the critical cysteine protease in coronavirus viral replication. Tea polyphenols are effective Mpro inhibitors. Therefore, we aim to isolate and synthesize more novel tea polyphenols from Zhenghedabai (ZHDB) white tea methanol-water (MW) extracts that might inhibit COVID-19. Through molecular networking, 33 compounds were identified and divided into 5 clusters. Further, natural products molecular network (MN) analysis showed that MN1 has new phenylpropanoid-substituted ester-catechin (PSEC), and MN5 has the important basic compound type hydroxycinnamoylcatechins (HCCs). Thus, a new PSEC (1, PSEC636) was isolated, which can be further detected in 14 green tea samples. A series of HCCs were synthesized (2-6), including three new acetylated HCCs (3-5). Then we used surface plasmon resonance (SPR) to analyze the equilibrium dissociation constants (KD) for the interaction of 12 catechins and Mpro. The KD values of PSEC636 (1), EGC-C (2), and EC-CDA (3) were 2.25, 2.81, and 2.44 µM, respectively. Moreover, compounds 1, 2, and 3 showed the potential Mpro inhibition with IC50 5.95 ± 0.17, 9.09 ± 0.22, and 23.10 ± 0.69 µM, respectively. Further, we used induced fit docking (IFD), binding pose metadynamics (BPMD), and molecular dynamics (MD) to explore the stable binding pose of Mpro-1, showing that 1 could tightly bond with the amino acid residues THR26, HIS41, CYS44, TYR54, GLU166, and ASP187. The computer modeling studies reveal that the ester, acetyl, and pyrogallol groups could improve inhibitory activity. Our research suggests that these catechins are effective Mpro inhibitors, and might be developed as therapeutics against COVID-19.

7.
Acs Food Science & Technology ; 1(10):1776-1786, 2021.
Article in English | Web of Science | ID: covidwho-2106317

ABSTRACT

Mango processing waste (MPW) is an inexpensive and rich source of valuable substances. Hence, the mango kernel powder (MKP) from four cultivars (Chausa, Neelum, Barahmasi, and Dashehari) was characterized for the selection of the best cultivar. The MKP of the best cultivar (Dashehari) was analyzed for the profiling of polyphenols using LC-MS/MS in both modes of ionization (positive and negative) and indicated the presence of 50 compounds with specific retention times. After identification, gallic acid (GA), an important industrial compound, was targeted and purified followed by its confirmation using NMR (600 MHz) and HRMS. The antioxidant activity (IC50: 1.96 mu g/mL) of extracted GA proposes its use as a natural antioxidant in novel food formulations. Additionally, SARS-CoV-2 main protease (M-pro) was selected for molecular docking based virtual screening of seven major polyphenols (MKP), and the results were compared with hydroxychloroquine. The docking scores of targeted polyphenols revealed that three compounds (epicatechin, mangiferin, and quercetin) exhibited appreciable proteolytic activity against M-pro. In this way, it is a favorable approach toward environmental safety on the standpoint of green chemistry owing to the use of food processing waste and elimination of the waste dumping/composting problems.

8.
Journal of Molecular Structure ; : 134507, 2022.
Article in English | ScienceDirect | ID: covidwho-2105616

ABSTRACT

This study was designed to synthesize hybridizing molecules starting from ciprofloxacin and norfloxacin by enhancing their biological activity with tetrazoles. The synthesized compounds were investigated in the interaction with the target enzyme of fluoroquinolones (DNA gyrase) and COVID-19 main protease using molecular similarity, molecular docking, and QSAR studies. A QSAR study was carried out to explore the antibacterial activity of our compounds over Staphylococcus aureus a QSAR study, using descriptors obtained from the docking with DNA gyrase, in combination with steric type descriptors, was done obtaining good statistical parameters (R2=87.00, QLMO2=71.67, and QEXT2=73.49) to support our results. The binding interaction of our compounds with the CoV-2-Mpro was done by molecular docking and were compared with different covalent and non-covalent inhibitors of this enzyme. For the docking studies we used several crystallographic structures of the CoV-2-Mpro. The interaction energy values and binding mode with several key residues, by our compounds, support the capability of them to be CoV-2-Mpro inhibitors. The characterization of the compounds was completed using FT-IR, 1H-NMR, 13C-NMR, 19F-NMR and HRMS spectroscopic methods. The results showed that compounds 1, 4, 5, 10 and 12 had the potential to be further studied as new antibacterial and antiviral compounds

9.
J Biomol Struct Dyn ; : 1-13, 2022 Nov 11.
Article in English | MEDLINE | ID: covidwho-2106895

ABSTRACT

The new health crises caused by SARS-CoV-2 have resulted in millions of deaths worldwide. First discovered in November 2021, the omicron variant is more transmissible and is able to evade the immune system better than other previously identified SARS-CoV-2 variants, leading to a spike in cases. Great efforts have been made to discover inhibitors against SARS-CoV-2. Main protease (Mpro) inhibitors are considered promising anti-SARS-CoV-2 agents. The U.S. FDA has issued an Emergency Use Authorization for ritonavir-boosted nirmatrelvir. Nirmatrelvir is the first orally bioavailable inhibitor of SARS-CoV-2 Mpro. There is an urgent need to monitor the mutations and solve the problem of resistance, especially omicron Mpro, which contains one mutation - P132H. In the present study, 132,57 phytochemicals from 80 medicinal plants grown in Saudi Arabia were docked into the active site of Mpro omicron variant. Free binding energies were also calculated. This led to the discovery of five phytochemicals that showed better docking scores than the bound ligand nirmatrelvir. In addition, these molecules exhibited favorable free binding energies. The stability of compounds 1-5 with the protein was studied using molecular dynamics (MD) simulations. These compounds showed acceptable ADMET properties. The results were compared with the wild type. These candidates could be envisioned as new hits against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

10.
J Biomol Struct Dyn ; : 1-12, 2022 Nov 14.
Article in English | MEDLINE | ID: covidwho-2106894

ABSTRACT

Since the main protease (Mpro) is crucial for the COVID-19 virus replication and transcription, searching for Mpro inhibitors is one possible treatment option. In our study, 258 small molecules were collected from lung-related herbal medicines, and their structures were optimized with the B3LYP-D3/6-31G* method. After the molecular docking with Mpro, we selected the top 20 compounds for the further geometry optimization with the larger basis sets. After the further molecular docking, the top eight compounds were screened out. Then we performed molecular dynamics simulations and binding free energy calculations to determine stability of the complexes. Our results show that mulberrofuran G, Xambioona, and kuwanon D can bind Mpro well. In quantum chemistry studies, such as ESP and CDFT analyses, the compounds properties are predicted. Additionally, the drug-likeness analyses and ADME studies on these three candidate compounds verified that all of them conform to Libinski's rule and may be drug-like compounds.

11.
J Biomol Struct Dyn ; : 1-16, 2022 Nov 11.
Article in English | MEDLINE | ID: covidwho-2106893

ABSTRACT

Bioactive compounds found in plants also have pharmacological antiviral effects. Berberine (BBR), an alkaloid found naturally in plants, is one of the phytochemicals with a wide range of biological activities, including antiviral, anticancer, anti-inflammatory and anti-inflammatory. In this study, we firstly aimed to predict pIC50 values for selcted compounds and then extract the binding patterns of berberine and its derivatives in the Sars Cov-2 Master Protease structure via employing molecular docking approache. Our results showed that berberine and its derivatives have good binding affinities towared Sars Cov2 main protease protein. Based on docking results the pharamaccokinetic studies for berberine, berberrubine, demethylen-berberine, jatrorrhizin, and thalifendine, were conducted and showed a good pharamacokinetic properties as an oral drugs. For deep inspection, we utiilized molecular dynmaics simulation to examine the Sars Cov2 main protease-ligand stabilities. The molecular dynamics simulation and PCA investigations revealed that thalifendine have a strong willing to act as good bindinder to SARS-CoV-2 protease. Further, the network based pharamacology showed that these drugs mediate different pathways such as human T-cell leukemia virus 1 infection, viral carcinogenesis, human immunodeficiency virus 1 infection, kaposi sarcoma-associated herpesvirus infection and epstein-Barr virus infection.The findings of this study have an important recomendation for thalifendine for more in vivo and in vitro studies to work.Communicated by Ramaswamy H. Sarma.

12.
J Mol Model ; 28(12): 380, 2022 Nov 07.
Article in English | MEDLINE | ID: covidwho-2103921

ABSTRACT

In response to the COVID-19 pandemic, and the lack of effective and safe antivirals against it, we adopted a new approach in which food supplements with vital antiviral characteristics, low toxicity, and fast excretion have been targeted. The structures and chemical properties of the food supplements were compared to the promising antivirals against SARS-COV-2. Our goal was to exploit the food supplements to mimic the topical antivirals' functions but circumventing their severe side effects, which has limited the necessary dosage needed to exhibit the desired antiviral activity. On this line, after a comparative structural analysis of the chemicals mentioned above, and investigation of their potential mechanisms of action, we selected caffeine and some compounds of the vitamin B family and further applied molecular modeling techniques to evaluate their interactions with the RDB domain of the Spike protein of SARS-CoV-2 (SC2Spike) and its corresponding binding site on human ACE-2 (HssACE2). Our results pointed to vitamins B1 and B6 in the neutral form as potential binders to the HssACE2 RDB binding pocket that might be able to impair the SARS-CoV-2 mechanism of cell invasion, qualifying as potential leads for experimental investigation against COVID-19.


Subject(s)
COVID-19 , Humans , COVID-19/drug therapy , SARS-CoV-2 , Pyridoxamine , Thiamine/metabolism , Pandemics , Caffeine/pharmacology , Niacinamide , Molecular Docking Simulation , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Drug Design , Vitamins
13.
Vitamins and Hormones ; 2022.
Article in English | ScienceDirect | ID: covidwho-2104210

ABSTRACT

In the last few years, the significance of antioxidant compounds and their properties has attracted great interest from the scientific community. The role of an antioxidant in managing & regulating oxidative stress and also in the protection of the human body from severe adverse effects due to excess release of free radicles or reactive oxygen species (ROS) is remarkable. From aiding protection & combating severe illnesses such as cancer, neurodegeneration, aging, and diabetes to being a vital part of the treatment of SARs-CoV-19 is of great importance. Therefore, the study of anti-oxidants is of great importance in human sustenance. Additionally, molecular docking techniques and their various mathematical features help in understanding the molecular interactions of anti-oxidants based on their lowest binding energy. The evaluation of the binding score between two constituent molecules will provide insight as to the binding process and also suggest possible novel therapeutic targets for the treatment of diseases. In this chapter, we will discuss the significance of molecular docking techniques in the study of antioxidant compounds.

14.
Immunotherapeutics, Vol. 129 ; : 275-379, 2022.
Article in English | Web of Science | ID: covidwho-2102163

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmissions are occurring rapidly;it is raising the alarm around the globe. Though vaccines are currently available, the evolution and mutations in the SARS-CoV-2 threaten available vaccines' significance. The drugs are still undergoing clinical trials, and certain medications are approved for "emergency use" or as an "off-label" drug during the pandemic. These drugs have been effective yet accommodating side effects, which also can be lethal. Complementary and alternative medicine is highly demanded since it embraces a holistic approach. Since ancient times, natural products have been used as drugs to treat various diseases in the medical field and are still widely practiced. Medicinal plants contain many active compounds that serve as the key to an effective drug design. The Kabasura kudineer and Nilavembu kudineer are the two most widely approved formulations to treat COVID-19. However, the mechanism of these formulations is not well known. The proposed study used a network pharmacology approach to understand the immune-boosting mechanism by the Kabasura kudineer, Nilavembu kudineer, and JACOM in treating COVID-19. The plants and phytochemical chemical compounds in the Kabasura kudineer, Nilavembu kudineer, and JACOM were obtained from the literature. The Swiss target prediction algorithm was used to predict the targets for these phytochemical compounds. The common genes for the COVID-19 infection and the drug targets were identified. The gene-gene interaction network was constructed to understand the interactions between these common genes and enrichment analyses to determine the biological process, molecular functions, cellular functions, pathways involved, etc. Finally, virtual screening and molecular docking studies were performed to identify the most potential targets and significant phytochemical compounds to treat the COVID-19. The present study identified potential targets as ACE, Cathepsin L, Cathepsin B, Cathepsin K, DPP4, EGFR, HDAC2, IL6, RIPK1, and VEGFA. Similarly, betulinic acid, 5 ''-(2 ''''-Hydroxybenzyl) uvarinol, antofine, (S)-10-methyloctyl caffeate, (Z)-3-phenyl-2-propenal, 7-oxo-10 alpha-cucurbitadienol, and PLX-4720 collectively to be potential treatment agents for COVID-19.

15.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 39(5): 1005-1014, 2022 Oct 25.
Article in Chinese | MEDLINE | ID: covidwho-2100336

ABSTRACT

We aim to screen out the active components that may have therapeutic effect on coronavirus disease 2019 (COVID-19) from the severe and critical cases' prescriptions in the "Coronavirus Disease 2019 Diagnosis and Treatment Plan (Trial Ninth Edition)" issued by the National Health Commission of the People's Republic of China and explain its mechanism through the interactions with proteins. The ETCM database and SwissADME database were used to screen the active components contained in 25 traditional Chinese medicines in 3 prescriptions, and the PDB database was used to obtain the crystal structures of 4 proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Molecular docking was performed using Autodock Vina and molecular dynamics simulations were performed using GROMACS. Binding energy results showed that 44 active ingredients including xambioona, gancaonin L, cynaroside, and baicalin showed good binding affinity with multiple targets of SARS-CoV-2, while molecular dynamics simulations analysis showed that xambioona bound more tightly to the nucleocapsid protein of SARS-CoV-2 and exerted a potent inhibitory effect. Modern technical methods are used to study the active components of traditional Chinese medicine and show that xambioona is an effective inhibitor of SARS-CoV-2 nucleocapsid protein, which provides a theoretical basis for the development of new anti-SARS-CoV-2 drugs and their treatment methods.


Subject(s)
COVID-19 , Humans , COVID-19/drug therapy , SARS-CoV-2 , Molecular Docking Simulation , Medicine, Chinese Traditional , Molecular Dynamics Simulation , Nucleocapsid Proteins , Antiviral Agents/therapeutic use , Antiviral Agents/chemistry , Antiviral Agents/pharmacology
16.
Molecules ; 27(21)2022 Nov 04.
Article in English | MEDLINE | ID: covidwho-2099670

ABSTRACT

Since there is an urgent need for novel treatments to combat the current coronavirus disease 2019 (COVID-19) pandemic, in silico molecular docking studies were implemented as an attempt to explore the ability of selected bioactive constituents of extra virgin olive oil (EVOO) to act as potent SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) antiviral compounds, aiming to explore their ability to interact with SARS-CoV-2 Spike key therapeutic target protein. Our results suggest that EVOO constituents display substantial capacity for binding and interfering with Spike (S) protein, both wild-type and mutant, via the receptor-binding domain (RBD) of Spike, or other binding targets such as angiotensin-converting enzyme 2 (ACE2) or the RBD-ACE2 protein complex, inhibiting the interaction of the virus with host cells. This in silico study provides useful insights for the understanding of the mechanism of action of the studied compounds at a molecular level. From the present study, it could be suggested that the studied active phytochemicals could potentially inhibit the Spike protein, contributing thus to the understanding of the role that they can play in future drug designing and the development of anti-COVID-19 therapeutics.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Spike Glycoprotein, Coronavirus/metabolism , Olive Oil , Molecular Docking Simulation , COVID-19/drug therapy , Peptidyl-Dipeptidase A/metabolism , Binding Sites , Protein Binding
17.
Molecules ; 27(21)2022 Oct 31.
Article in English | MEDLINE | ID: covidwho-2099665

ABSTRACT

Synthesis of sulfonamide through an indirect method that avoids contamination of the product with no need for purification has been carried out using the indirect process. Here, we report the synthesis of a novel sulfonamide compound, ({4-nitrophenyl}sulfonyl)tryptophan (DNSPA) from 4-nitrobenzenesulphonylchloride and L-tryptophan precursors. The slow evaporation method was used to form single crystals of the named compound from methanolic solution. The compound was characterized by X-ray crystallographic analysis and spectroscopic methods (NMR, IR, mass spectrometry, and UV-vis). The sulfonamide N-H NMR signal at 8.07-8.09 ppm and S-N stretching vibration at 931 cm-1 indicate the formation of the target compound. The compound crystallized in the monoclinic crystal system and P21 space group with four molecules of the compound in the asymmetric unit. Molecular aggregation in the crystal structure revealed a 12-molecule aggregate synthon sustained by O-H⋯O hydrogen bonds and stabilised by N-H⋯O intermolecular contacts. Experimental studies were complemented by DFT calculations at the B3LYP/6-311++G(d,p) level of theory. The computed structural and spectroscopic data are in good agreement with those obtained experimentally. The energies of interactions between the units making up the molecule were calculated. Molecular docking studies showed that DNSPA has a binding energy of -6.37 kcal/mol for E. coli DNA gyrase (5MMN) and -6.35 kcal/mol for COVID-19 main protease (6LU7).


Subject(s)
COVID-19 , Tryptophan , Humans , Quantum Theory , Models, Molecular , Molecular Docking Simulation , Escherichia coli , Spectroscopy, Fourier Transform Infrared , Sulfonamides
18.
Physical Chemistry Research ; 11(3):623-629, 2023.
Article in English | Scopus | ID: covidwho-2100687

ABSTRACT

Selected monoclonal antibody molecules were conducted using the antibody-antigen docking mode, as well as the antibody-antigen docking approach. The objective of the study was to check the effects of Cetuximab COVID-19 proteins (Nsp15 and 3CLpro) by using antibody-antigen docking mode, as well as the antibody-antigen docking approach. The results of molecular docking revealed that Cetuximab, a cancer-fighting antibody, ranks first among antibodies to both COVID-19 proteins (Nsp15 and 3CLpro). In cetuximab-3CLpro and cetuximab-Nsp15 complexes, the antigen interacts with both antibody chains, H and L. According to the findings, Cetuximab can be added to the COVID-19 treatment protocol, which may have the desired effect of inhibiting viral replication and decreasing mortality by targeting COVID-19 proteins (Nsp15 and 3CLpro). Validation of these computational findings will require additional in vitro and in vivo research, which can be considered as a contribution in the field of biotechnology © 2023, Physical Chemistry Research.All Rights Reserved.

19.
Química Nova ; 2022.
Article in English | Web of Science | ID: covidwho-2100670

ABSTRACT

The pandemic caused by the new coronavirus has resulted in a global health emergency and has prompted an urgent need for new treatment strategies. No target-specific drugs are currently available for SARS-CoV-2, but new drug candidates targeting the viral replication cycle are being explored. A prime target of drug-discovery efforts is the SARS-CoV-2 main protease (Mpro). In this work, we identified a potential inhibitor for SARS-CoV-2 main protease using in silico methodologies. Molecular docking and molecular dynamics studies were carried out to ascertain the inhibitory action of a and 13 anomers of Punicalagin from fruit peel of Punica granatum against the Mpro protease. The molecular dynamics results revealed that the 13-anomeric configuration of punicalagin allowed access to more hydrogen bonds and hydrophobic interaction leading to higher selectivity and specificity of 13-anomer than a-anomer. Therefore, the 13-anomer of Punicalagin could act as potential inhibitor against the main protease of SARS-CoV-2 and may act as a potential drug candidate.

20.
BMC Chem ; 16(1): 82, 2022 Nov 02.
Article in English | MEDLINE | ID: covidwho-2098444

ABSTRACT

Computational tools in investigating of spectral heterocyclic compounds ranges based on pyrimidine­2­thiones, take some importance in identifying their molecular and electronic behavior. Some charcoal heterocyclic compounds were previously synthesized in our laboratory and their experimental results were compared with the computational evaluation. Computational spectroscopic analytical items (IR, NMR and UV-Vis) were calculated using the more popular DFT methods and the predicted results were compared with the reported experimental ones. Quantum and chemical parameters were calculated and molecular electrostatic surface potential (MEP) was studied which predicted the highly electronic sites around the compounds. Some molecular properties (ionization energy, electron affinity, energy gap, hardness, electronegativity, electrophilicity index, static dipole moment and average linear polarizability) of these Schiff bases which were computed at B3LYP/6-31G(d,p) level in aqueous phase. Benchmark analysis was performed for three ab initio functionals such B3LYP, BPV86 and B3PW91 methods to explain the data resulted from NMR spectra. The docking study of some selected previously synthesized compounds was performed using the viral Mpro enzyme protein in compared to a k36 reference ligand inhibitor. The study indicated the ability of the synthesized compounds to form H-bond and hydrophobic (VDW, π-alkyl and π-sulfur) interactions with Mpro enzyme receptor with high inhibition effect of compound L2.

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