P.179 A cell-based assay for evaluating potential antiviral agents against HCV

2006 ◽  
Vol 36 ◽  
pp. S116
Author(s):  
S. Aviel ◽  
J. Ben-Porath ◽  
E. Mishori ◽  
D. Slama ◽  
N. Cohen ◽  
...  
Keyword(s):  
Antiviral Agents ◽  
A Cell

scholarly journals Human Coronaviruses: Counteracting the Damage by Storm

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1457
Author(s):  
Dewald Schoeman ◽  
Burtram C. Fielding
Keyword(s):  
Immune Response ◽  
Severe Disease ◽  
Antiviral Agents ◽  
The Elderly ◽  
Highly Pathogenic ◽  
Vaccine Responses ◽  
Cell Mediated Immune Response ◽  
Inhibition Antibody ◽  
A Cell ◽  
Human Coronaviruses

Over the past 18 years, three highly pathogenic human (h) coronaviruses (CoVs) have caused severe outbreaks, the most recent causative agent, SARS-CoV-2, being the first to cause a pandemic. Although much progress has been made since the COVID-19 pandemic started, much about SARS-CoV-2 and its disease, COVID-19, is still poorly understood. The highly pathogenic hCoVs differ in some respects, but also share some similarities in clinical presentation, the risk factors associated with severe disease, and the characteristic immunopathology associated with the progression to severe disease. This review aims to highlight these overlapping aspects of the highly pathogenic hCoVs—SARS-CoV, MERS-CoV, and SARS-CoV-2—briefly discussing the importance of an appropriately regulated immune response; how the immune response to these highly pathogenic hCoVs might be dysregulated through interferon (IFN) inhibition, antibody-dependent enhancement (ADE), and long non-coding RNA (lncRNA); and how these could link to the ensuing cytokine storm. The treatment approaches to highly pathogenic hCoV infections are discussed and it is suggested that a greater focus be placed on T-cell vaccines that elicit a cell-mediated immune response, using rapamycin as a potential agent to improve vaccine responses in the elderly and obese, and the potential of stapled peptides as antiviral agents.

scholarly journals Identification and Evaluation of Potential SARS-CoV-2 Antiviral Agents Targeting mRNA Cap Guanine N7-Methyltransferase

2021 ◽  
Author(s):  
Renata Kasprzyk ◽  
Tomasz J. Spiewla ◽  
miroslaw smietanski ◽  
Sebastian Golojuch ◽  
Laura Vangeel ◽  
...  
Keyword(s):  
Antiviral Agents ◽  
Therapeutic Interventions ◽  
Binding Assays ◽  
Inhibitory Effects ◽  
Dot Blot ◽  
Rp Hplc ◽  
Structure Activity ◽  
Mrna Capping ◽  
New Ideas ◽  
A Cell

SARS-CoV-2, the cause of the currently ongoing COVID-19 pandemic, encodes its own mRNA capping machinery. Insights into this capping system may provide new ideas for therapeutic interventions and drug discovery. In this work, we employ a previously developed Py-FLINT screening approach to study the inhibitory effects of compounds against the cap guanine N7-methyltransferase enzyme, which is involved in SARS-CoV-2 mRNA capping. We screened five commercially available libraries (7039 compounds in total) to identify 83 inhibitors with IC50 < 50 μM, which were further validated using RP HPLC and dot blot assays. Novel fluorescence anisotropy binding assays were developed to examine the targeted binding site. The inhibitor structures were analyzed for structure-activity relationships in order to define common structural patterns. Finally, the most potent inhibitors were tested for antiviral activity on SARS-CoV-2 in a cell based assay<br>

scholarly journals Griffithsin and Carrageenan Combination Results in Antiviral Synergy against SARS-CoV-1 and 2 in a Pseudoviral Model

Marine Drugs ◽  
2021 ◽  
Vol 19 (8) ◽  
pp. 418
Author(s):  
Sahar Alsaidi ◽  
Nadjet Cornejal ◽  
Oneil Mahoney ◽  
Claudia Melo ◽  
Neeharika Verma ◽  
...  
Keyword(s):  
Combination Index ◽  
Antiviral Agents ◽  
Therapeutic Index ◽  
Antagonistic Effect ◽  
Sulfated Polysaccharides ◽  
Synergistic Activity ◽  
Species Barrier ◽  
Half Maximal Effective Concentration ◽  
A Cell ◽  
Inhibition Analysis

Over 182 million confirmed cases of COVID-19 and more than 4 million deaths have been reported to date around the world. It is essential to identify broad-spectrum antiviral agents that may prevent or treat infections by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but also by other coronaviruses that may jump the species barrier in the future. We evaluated the antiviral selectivity of griffithsin and sulfated and non-sulfated polysaccharides against SARS-CoV-1 and SARS-CoV-2 using a cytotoxicity assay and a cell-based pseudoviral model. The half-maximal cytotoxic concentration (CC50) and half-maximal effective concentration (EC50) were determined for each compound, using a dose-response-inhibition analysis on GraphPad Prism v9.0.2 software (San Diego, CA, USA). The therapeutic index (TI = CC50/EC50) was calculated for each compound. The potential synergistic, additive, or antagonistic effect of different compound combinations was determined by CalcuSyn v1 software (Biosoft, Cambridge, UK), which estimated the combination index (CI) values. Iota and lambda carrageenan showed the most potent antiviral activity (EC50 between 3.2 and 7.5 µg/mL). Carrageenan and griffithsin combinations exhibited synergistic activity (EC50 between 0.2 and 3.8 µg/mL; combination index <1), including against recent SARS-CoV-2 mutations. The griffithsin and carrageenan combination is a promising candidate to prevent or treat infections by SARS-CoV-1 and SARS-CoV-2.

scholarly journals Use of a Prenylation Inhibitor as a Novel Antiviral Agent

1998 ◽  
Vol 72 (11) ◽  
pp. 9303-9306 ◽  
Author(s):  
Jeffrey S. Glenn ◽  
James C. Marsters ◽  
Harry B. Greenberg
Keyword(s):  
Particle Production ◽  
Molecular Genetic ◽  
Antiviral Agents ◽  
Antiviral Agent ◽  
Dependent Manner ◽  
Critical Determinant ◽  
Particle Assembly ◽  
Delta Antigen ◽  
A Cell ◽  
Severe Liver Disease

ABSTRACT No specific therapy exists for hepatitis delta virus (HDV), which can cause severe liver disease. Molecular genetic studies have implicated the prenylation site of large delta antigen as a critical determinant of HDV particle assembly. We have established a cell culture model which produces HDV-like particles, and we show that delta antigen prenylation can be pharmacologically inhibited by the prenylation inhibitor BZA-5B. Furthermore, BZA-5B specifically abolishes particle production in a dose-dependent manner. These results demonstrate that the use of such a prenylation inhibitor-based antiviral therapy may be feasible and identify a novel class of potential antiviral agents.

scholarly journals Multidrug treatment with nelfinavir and cepharanthine against COVID-19

2020 ◽  
Author(s):  
Hirofumi Ohashi ◽  
Koichi Watashi ◽  
Wakana Saso ◽  
Kaho Shionoya ◽  
Shoya Iwanami ◽  
...  
Keyword(s):  
Combined Treatment ◽  
Antiviral Agents ◽  
Hiv Protease ◽  
Viral Attachment ◽  
Main Protease ◽  
Culture Model ◽  
Progression Of Disease ◽  
A Cell ◽  
Approved Drugs

SummaryAntiviral treatments targeting the emerging coronavirus disease 2019 (COVID-19) are urgently required. We screened a panel of already-approved drugs in a cell culture model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and identified two new antiviral agents: the HIV protease inhibitor Nelfinavir and the anti-inflammatory drug Cepharanthine. In silico modeling shows Nelfinavir binds the SARS-CoV-2 main protease consistent with its inhibition of viral replication, whilst Cepharanthine inhibits viral attachment and entry into cells. Consistent with their different modes of action, in vitro assays highlight a synergistic effect of this combined treatment to limit SARS-CoV-2 proliferation. Mathematical modeling in vitro antiviral activity coupled with the known pharmacokinetics for these drugs predicts that Nelfinavir will facilitate viral clearance. Combining Nelfinavir/Cepharanthine enhanced their predicted efficacy to control viral proliferation, to ameliorate both the progression of disease and risk of transmission. In summary, this study identifies a new multidrug combination treatment for COVID-19.

scholarly journals Spike protein of SARS-COV-2 as a potential target for phytochemical constituents: A literature review

2021 ◽  
Vol 4 (2) ◽  
pp. 124-130
Author(s):  
Maira Ahmad ◽  
Sehrish Rashid ◽  
Taseer Ahmad
Keyword(s):  
Antiviral Agents ◽  
Spike Protein ◽  
Structural Proteins ◽  
Effective Control ◽  
Computational Studies ◽  
Viral Attachment ◽  
Related Data ◽  
A Cell ◽  
Phytochemical Constituents

SARS-CoV-2 belongs to well-known SARS Coronaviridae family. One of the main structural proteins of SARS-CoV-2 is the spike protein that is present around the surface of a viral cell and plays an essential role in viral attachment, fusion and invasion in host cell. Once a virus invades a cell, it replicates and infects other cells. The fundamental role of spike protein in the progression of viral infection has led to an increased interest in exploring agents that target the viral spike protein for effective control of CoVID-19. The related data from published articles reviewed and numerous phytochemicals that reportedly target the spike proteins of coronaviruses by computational studies briefly discussed. These active constituents possess the potential to develop as therapeutic and antiviral agents against SARS-CoV-2.

scholarly journals Identification and Evaluation of Potential SARS-CoV-2 Antiviral Agents Targeting mRNA Cap Guanine N7-Methyltransferase

2021 ◽  
Author(s):  
Renata Kasprzyk ◽  
Tomasz J. Spiewla ◽  
miroslaw smietanski ◽  
Sebastian Golojuch ◽  
Laura Vangeel ◽  
...  
Keyword(s):  
Antiviral Agents ◽  
Therapeutic Interventions ◽  
Binding Assays ◽  
Inhibitory Effects ◽  
Dot Blot ◽  
Rp Hplc ◽  
Structure Activity ◽  
Mrna Capping ◽  
New Ideas ◽  
A Cell

SARS-CoV-2, the cause of the currently ongoing COVID-19 pandemic, encodes its own mRNA capping machinery. Insights into this capping system may provide new ideas for therapeutic interventions and drug discovery. In this work, we employ a previously developed Py-FLINT screening approach to study the inhibitory effects of compounds against the cap guanine N7-methyltransferase enzyme, which is involved in SARS-CoV-2 mRNA capping. We screened five commercially available libraries (7039 compounds in total) to identify 83 inhibitors with IC50 < 50 μM, which were further validated using RP HPLC and dot blot assays. Novel fluorescence anisotropy binding assays were developed to examine the targeted binding site. The inhibitor structures were analyzed for structure-activity relationships in order to define common structural patterns. Finally, the most potent inhibitors were tested for antiviral activity on SARS-CoV-2 in a cell based assay<br>

Effect of Niacin on Mitochondria of Allium Cepa Root Cells

1967 ◽  
Vol 25 ◽  
pp. 78-79
Author(s):  
M. Arif Hayat
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Hydrogen Transfer ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Nicotinamide Adenine ◽  
Root Tips ◽  
Root Cells ◽  
Transfer Processes ◽  
Standard Procedures ◽  
A Cell ◽  
Critical Interest

Although it is recognized that niacin (pyridine-3-carboxylic acid), incorporated as the amide in nicotinamide adenine dinucleotide (NAD) or in nicotinamide adenine dinucleotide phosphate (NADP), is a cofactor in hydrogen transfer in numerous enzyme reactions in all organisms studied, virtually no information is available on the effect of this vitamin on a cell at the submicroscopic level. Since mitochondria act as sites for many hydrogen transfer processes, the possible response of mitochondria to niacin treatment is, therefore, of critical interest.Onion bulbs were placed on vials filled with double distilled water in the dark at 25°C. After two days the bulbs and newly developed root system were transferred to vials containing 0.1% niacin. Root tips were collected at ¼, ½, 1, 2, 4, and 8 hr. intervals after treatment. The tissues were fixed in glutaraldehyde-OsO4 as well as in 2% KMnO4 according to standard procedures. In both cases, the tissues were dehydrated in an acetone series and embedded in Reynolds' lead citrate for 3-10 minutes.

Ultrastructure of melanocyte-keratinocyte interactions and pigment transfer in vitro

1978 ◽  
Vol 36 (2) ◽  
pp. 650-651
Author(s):  
Raul I. Garcia ◽  
Evelyn A. Flynn ◽  
George Szabo
Keyword(s):  
Direct Injection ◽  
Skin Pigmentation ◽  
Freeze Fracture ◽  
Pigment Granule ◽  
Time Lapse ◽  
Ultrastructural Level ◽  
Lanthanum Tracer ◽  
A Cell

Skin pigmentation in mammals involves the interaction of epidermal melanocytes and keratinocytes in the structural and functional unit known as the Epidermal Melanin Unit. Melanocytes(M) synthesize melanin within specialized membrane-bound organelles, the melanosome or pigment granule. These are subsequently transferred by way of M dendrites to keratinocytes(K) by a mechanism still to be clearly defined. Three different, though not necessarily mutually exclusive, mechanisms of melanosome transfer have been proposed: cytophagocytosis by K of M dendrite tips containing melanosomes, direct injection of melanosomes into the K cytoplasm through a cell-to-cell pore or communicating channel formed by localized fusion of M and K cell membranes, release of melanosomes into the extracellular space(ECS) by exocytosis followed by K uptake using conventional phagocytosis. Variability in methods of transfer has been noted both in vivo and in vitro and there is evidence in support of each transfer mechanism. We Have previously studied M-K interactions in vitro using time-lapse cinemicrography and in vivo at the ultrastructural level using lanthanum tracer and freeze-fracture.

Dendritic cells of the human epidermis: immuno-electron microscopic studies of la antigen reactivity

1978 ◽  
Vol 36 (2) ◽  
pp. 644-645
Author(s):  
G. Rowden ◽  
M. G. Lewis ◽  
T. M. Phillips
Keyword(s):  
Dendritic Cells ◽  
Langerhans Cells ◽  
Cell Types ◽  
Cell Type ◽  
Electron Microscopic ◽  
La Antigen ◽  
Microscopic Studies ◽  
A Cell ◽  
C3 Receptors ◽  
Antigen Reactivity

Langerhans cells of mammalian stratified squamous epithelial have proven to be an enigma since their discovery in 1868. These dendritic suprabasal cells have been considered as related to melanocytes either as effete cells, or as post divisional products. Although grafting experiments seemed to demonstrate the independence of the cell types, much confusion still exists. The presence in the epidermis of a cell type with morphological features seemingly shared by melanocytes and Langerhans cells has been especially troublesome. This so called "indeterminate", or " -dendritic cell" lacks both Langerhans cells granules and melanosomes, yet it is clearly not a keratinocyte. Suggestions have been made that it is related to either Langerhans cells or melanocyte. Recent studies have unequivocally demonstrated that Langerhans cells are independent cells with immune function. They display Fc and C3 receptors on their surface as well as la (immune region associated) antigens.

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