Polymethine Dyes as Probes for Detecting the SARS-COV-2 Coronavirus: In silico Molecular Docking Study
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ABSTRACT:
SUBMITTER: Pronkin P
PROVIDER: S-EPMC8064416 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The ongoing spread of the COVID-19 coronavirus infection requires us to find new tools and methods for detecting and studying the infection and preventing morbidity (new analytical procedures and tests). With the aim of developing probes for the detection of SARS-CoV-2 coronavirus by modeling in silico (molecular docking), the noncovalent binding of cyanine and squarylium dyes with different molecular charges and different types of heterocyclic residues and substituents (42 compounds in total) with different variants of the NSP15 endoribonuclease of the SARS-CoV-2 coronavirus (COVID-19) of the original (wild) type and mutant types is studied. The interaction energies and spatial configurations of the dye molecules in complexes with NSP15 are determined. Some dyes with negative values of the total energy of the complex Etot are promising for further practical study as probes for coronavirus.
| S-EPMC9022896 | biostudies-literature
Project description:Methods to red-shift fluorophores have garnered considerable interest due to the broad utility of low energy light. The incorporation of silicon into xanthene and coumarin scaffolds has resulted in an array of visible and near-infrared fluorophores. Here, we extend this approach to polymethine dyes, another popular fluorophore class, performing experimental and computational analyses. We found that when oxygen was replaced with SiMe2, bathochromic shifts of up to 121 nm and fluorophores with emission above 900 nm were achieved.
| S-EPMC7552435 | biostudies-literature
Project description:Background The unique anthropological coronavirus which has been titled as SARS-CoV-2 was originally arisen in late 2019 in Wuhan, China affecting respiratory infection named as COVID-19. Coronavirus is disturbing human life in an exceptional method and has converted a public health global crisis. Natural products are ahead consideration due to the huge beneficial window and effective anti-inflammatory, immunomodulatory, antioxidant and antiviral possessions. Consequently, the present study was intended to display inhibition ability of natural products coumarins and their analogues against SARS coronavirus. Methods The present study, aims to forecast theoretical assembly for the protease of COVID-19 and to discover advance whether this protein may assist as a target for protease inhibitors such as psoralen, bergapten, imperatorin, heraclenin, heraclenol, saxalin, oxepeucedanin, angelicin, toddacoumaquinone, and aesculetin. The docking score of these natural coumarin analogues compared with standard Hydroxychloroquine. Whereas the 3D assembly of main protease of SARS coronavirus was forecast with SWISS MODEL web server, and molecular interaction studies amongst target protein and ligands were done with AutoDock Vina software. Results The study more exposed that all the inhibitors acquired with negative dock energy against the target protein. Molecular docking investigation displayed that natural coumarin analogue toddacoumaquinone displayed a remarkable inhibition ability with the binding energy of ?7.8 kcal/mol than other compounds against main protease of SARS coronavirus in intricate with ?-ketoamide (PDB ID: 5N5O). The synthetic coumarin analogue (1 m) also displayed the comparable inhibition ability with a binding energy of ?7.1 kcal/mol against main protease of SARS coronavirus in intricate with ?-ketoamide. Keeping the overhead results of ADME and toxicity, all tested compounds were recognized as drug-like nature, passing Lipinski’s “Rule of 5” with 0 violation except ?-ketoamide passes Lipinski’s “Rule of 5” with 1 violation MW > 500. The projected constraints are within the assortment of recognized values. Conclusions Based upon the results of the manifold sequence alliance, natural and synthetic coumarin binding sites were preserved. The present in silico examination thus, delivers structural awareness about the protease of COVID-19 and molecular relations with some of the recognised protease inhibitors.
| S-EPMC7505582 | biostudies-literature
Project description:Near-infrared (NIR) organic dyes have become important for many biomedical applications, including in vivo optical imaging. Conjugation of NIR fluorescent dyes to photosensitizing molecules (photosensitizers) holds strong potential for NIR fluorescence image guided photodynamic therapy (PDT) of cancer. Therefore, we were interested in investigating the photophysical properties, in vivo tumor-affinity and fluorescence imaging potential of a series of heterocyclic polymethine dyes, which could then be conjugated to certain PDT agents. For our present study, we selected a series of symmetrical polymethine dyes containing a variety of bis-N-substituted indole or benzindole moieties linked by linear conjugation with and without a fused substituted cyclohexene ring. The N-alkyl side chain at the C-terminal position was functionalized with sulfonic, carboxylic acid, methyl ester or hydroxyl groups. Although, among the parent cyanine dyes investigated, the commercially available, cyanine dye IR783 (3) (bis-indole-N-butylsulfonate)-polymethine dye with a cyclic chloro-cyclohexene moiety showed best fluorescence-imaging ability, based on its spectral properties (λAbs=782 nm, λFl=810 nm, ε = 261,000 M(-1)cm(-1), ΦFl≈0.08) and tumor affinity. In addition to 3, parent dyes IR820 and Cypate (6) were also selected and subjected to further modifications by introducing desired functional groups, which could enable further conjugation of the cyanine dyes to an effective photosensitizer HPPH developed in our laboratory. The synthesis and biological studies (tumor-imaging and PDT) of the resulting bifunctional conjugates are discussed in succeeding paper (Part-2 of this study).
| S-EPMC3767116 | biostudies-literature
Project description:SARS-CoV-2 has devastated the world with its rapid spread and fatality. The researchers across the globe are struggling hard to search a drug to treat this infection. Understanding the time constraint, the best approach is to study clinically approved drugs for control of this deadly pandemic of COVID 19. The repurposing of such drugs can be supported with the study of molecular interactions to enhance the possibility of application. The present work is a molecular docking study of proteins responsible for viral propagation namely 3Clpro, Nsp10/16, Spike protein, SARS protein receptor binding domain, Nsp 9 viral single strand binding protein and viral helicase. The protein through virus enters the host cell-human angiotensin-converting enzyme 2 (ACE2) receptor, is also used as a target for molecular docking. The docking was done with most discussed drugs for SARS-CoV-2 like Ritonavir, Lopinavir, Remdesivir, Chloroquine, Hydroxychloroquine (HCQ), routine antiviral drugs like Oseltamivir and Ribavirin. In addition, small molecules with anti-inflammatory actions like Mycophenolic acid (MPA), Pemirolast, Isoniazid and Eriodictyol were also tested. The generated data confirms the potential of Ritonavir, Lopinavir and Remdesivir as a therapeutic candidate against SARS-CoV-2. It is observed that Eriodictyol binds to almost all selected target proteins with good binding energy, suggesting its importance in treatment of COVID 19. Molecular interactions of Ritonavir, Lopinavir and Remdesivir against SARS-CoV-2 proteins enhanced their potential as a candidate drug for treatment of COVID-19. Eriodictyol had emerged as a new repurposing drug that can be used in COVID-19.
| S-EPMC7398085 | biostudies-literature
Project description:In the current spread of novel coronavirus (SARS-CoV-2), antiviral drug discovery is of great importance. AutoDock Vina was used to screen potential drugs by molecular docking with the structural protein and non-structural protein sites of new coronavirus. Ribavirin, a common antiviral drug, remdesivir, chloroquine and luteolin were studied. Honeysuckle is generally believed to have antiviral effects in traditional Chinese medicine. In this study, luteolin (the main flavonoid in honeysuckle) was found to bind with a high affinity to the same sites of the main protease of SARS-CoV-2 as the control molecule. Chloroquine has been proved clinically effective and can bind to the main protease; this may be the antiviral mechanism of this drug. The study was restricted to molecular docking without validation by molecular dynamics simulations. Interactions with the main protease may play a key role in fighting against viruses. Luteolin is a potential antiviral molecule worthy of attention.
| S-EPMC7205718 | biostudies-literature
Project description:Developing a safe and effective antiviral treatment takes a decade, however, when it comes to the coronavirus disease (COVID-19), time is a sensitive matter to slow the spread of the pandemic. Screening approved antiviral drugs against COVID-19 would speed the process of finding therapeutic treatment. The current study examines commercially approved drugs to repurpose them against COVID-19 virus main protease using structure-based in-silico screening. The main protease of the coronavirus is essential in the viral replication and is involved in polyprotein cleavage and immune regulation, making it an effective target when developing the treatment. A Number of approved antiviral drugs were tested against COVID-19 virus using molecular docking analysis by calculating the free natural affinity of the binding ligand to the active site pocket and the catalytic residues without forcing the docking of the ligand to active site. COVID-19 virus protease solved structure (PDB ID: 6LU7) is targeted by repurposed drugs. The molecular docking analysis results have shown that the binding of Remdesivir and Mycophenolic acid acyl glucuronide with the protein drug target has optimal binding features supporting that Remdesivir and Mycophenolic acid acyl glucuronide can be used as potential anti-viral treatment against COVID-19 disease.
| S-EPMC8173495 | biostudies-literature
Project description:OBJECTIVE:To explore potential natural products against severe acute respiratory syndrome coronavirus (SARS-CoV-2) via the study of structural and non-structural proteins of human coronaviruses. METHODS:In this study, we performed an in-silico survey of 25 potential natural compounds acting against SARS-CoV-2. Molecular docking studies were carried out using compounds against 3-chymotrypsin-like protease (3CLPRO), papain-like protease (PLPRO), RNA-dependent RNA polymerase (RdRp), non-structural protein (nsp), human angiotensin converting enzyme 2 receptor (hACE2R), spike glycoprotein (S protein), abelson murine leukemia viral oncogene homolog 1 (ABL1), calcineurin-nuclear factor of activated T-cells (NFAT) and transmembrane protease serine 2. RESULTS:Among the screened compounds, amentoflavone showed the best binding affinity with the 3CLPRO, RdRp, nsp13, nsp15, hACE2R. ABL1 and calcineurin-NFAT; berbamine with hACE2R and ABL1; cepharanthine with nsp10, nsp14, nsp16, S protein and ABL1; glucogallin with nsp15; and papyriflavonol A with PLPRO protein. Other good interacting compounds were juglanin, betulinic acid, betulonic acid, broussooflavan A, tomentin A, B and E, 7-methoxycryptopleurine, aloe emodin, quercetin, tanshinone I, tylophorine and furruginol, which also showed excellent binding affinity towards a number of target proteins. Most of these compounds showed better binding affinities towards the target proteins than the standard drugs used in this study. CONCLUSION:Natural products or their derivatives may be one of the potential targets to fight against SARS-CoV-2.
| S-EPMC8672856 | biostudies-literature
Project description:Inexpensive, simple, rapid diagnostics are necessary for efficient detection, treatment, and mitigation of COVID-19. Assays for SARS-CoV2 using reverse transcription polymerase chain reaction (RT-PCR) offer good sensitivity and excellent specificity, but are expensive, slowed by transport to centralized testing laboratories, and often unavailable. Antigen-based assays are inexpensive and can be rapidly mass-produced and deployed at point-of-care, with lateral flow assays (LFAs) being the most common format. While various manufacturers have produced commercially available SARS-Cov2 antigen LFAs, access to validated tests remains difficult or cost prohibitive in low-and middle-income countries. Herein, we present a visually read open-access LFA (OA-LFA) using commercially-available antibodies and materials for the detection of SARS-CoV-2. The LFA yielded a Limit of Detection (LOD) of 4 TCID50/swab of gamma irradiated SARS-CoV-2 virus, meeting the acceptable analytical sensitivity outlined by in World Health Organization target product profile. The open-source architecture presented in this manuscript provides a template for manufacturers around the globe to rapidly design a SARS-CoV2 antigen test.
| S-EPMC8580225 | biostudies-literature
Project description:The ongoing pandemic COVID-19 (COrona Virus Immuno Deficiency-2019) which is caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome-CoronaVirus-2) has emerged as a pandemic with 400,000 plus deaths till date. We do not have any drug or vaccine available for the inhibition of this deadly virus. The expedition for searching a potential drug or vaccine against COVID-19 will be of massive potential and favor. This study is focused on finding an effective natural origin compound which can put a check on the activity of this virus. We chose important proteins from the SARS-CoV-2 genome such as NSP4, NSP15 and RdRp along-with the human ACE2 receptor which is the first point of contact with the virus. Virtual screening and followed up molecular docking resulted in Baicalin and Limonin as the final lead molecules. 200 ns of MD simulation for each protein-ligand complex provides the insights that Baicalin has a potential to target NSP4, NSP15 and RdRp proteins. Limonin which is largely used in traditional Indian medicine system is found to inhibit the human ACE2 receptor (making it inefficient in binding to the receptor binding domain of SARS-CoV-2). Our studies propose Baicalin and Limonin in combination to be studied in vitro and in vivo against COVID-19. Communicated by Ramaswamy H. Sarma.
| S-EPMC7484580 | biostudies-literature