scholarly journals Evaluating the Effect of Amine-geldanamycin Hybrids on Antiviral Activity against Influenza Virus

2021 ◽  
pp. 71-82
Author(s):  
Thongchai Taechowisan ◽  
Tipparat Samsawat ◽  
Chanjira Jaramornburapong ◽  
Weerachai Phutdhawong ◽  
Waya S. Phutdhawong
Keyword(s):  
Influenza Virus ◽  
Molecular Docking ◽  
Antiviral Activity ◽  
Binding Free Energy ◽  
Antiviral Agents ◽  
Biological Properties ◽  
Virus Propagation ◽  
Cytotoxicity Activity ◽  
Ic50 Values ◽  
Chicken Eggs

Aims: The purpose of this study was to synthesis novel amine-geldanamycin hybrids (AGH) and evaluate their biological properties. Study Design: Experimental study. Place and Duration of Study: The study was carried out at the Department of Microbiology and Department of Chemistry, Faculty of Science, Silpakorn University, from December 2019 - November 2020. Methodology: Three new amine-geldanamycin hybrids (AGH); compounds 2 to 4 were synthesised by nucleophilic substitution of geldanamycin (1). The solubility, cytotoxicity, antiviral activity and molecular docking analyses were carried out. Results: The solubility of AGH in water was 1.918-5.571 mM, higher than that of compound 1. Compound 2 exhibited weak cytotoxicity activity against Vero and LLC-MK2 cells, with IC50 values of 229.19 and 330.58 µg/ml, respectively. All compounds inhibited influenza virus propagation in embryonated chicken eggs at the lowest amount of 1.25 µg per egg. They interacted positively with Hsp90, showing a binding free energy (DG) of -112.00 to -116.34 kcal/mol, which indicated lower Hsp90 affinity compared with that of geldanamycin (-133.06 kcal/mol) and 17-dimethylamino ethylamino-17-demethoxygeldanamycin (-136.55 kcal/mol), despite being bound in the similar active site. For the viral absorption, only AGH inhibited hemagglutination at a concentration of 25 µg/ml. Conclusion: The study findings revealed, through molecular docking analysis, that the development of AGH improved the antiviral activity. The AGH inhibited not only influenza virus propagation, but also viral absorption. Therefore, AGH could be considered a new choice for antiviral agents.

scholarly journals Synthesis and Antiviral Evaluation of Nucleoside Analogues Bearing One Pyrimidine Moiety and Two D-Ribofuranosyl Residues

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3678
Author(s):  
Olga V. Andreeva ◽  
Bulat F. Garifullin ◽  
Vladimir V. Zarubaev ◽  
Alexander V. Slita ◽  
Iana L. Yesaulkova ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Antiviral Activity ◽  
Theoretical Calculations ◽  
Nucleoside Analogs ◽  
Coxsackievirus B3 ◽  
Nucleoside Analogues ◽  
Moderate Activity ◽  
Coat Proteins ◽  
Influenza Virus A ◽  
Ic50 Values

A series of 1,2,3-triazolyl nucleoside analogues in which 1,2,3-triazol-4-yl-β-d-ribofuranosyl fragments are attached via polymethylene linkers to both nitrogen atoms of the heterocycle moiety (uracil, 6-methyluracil, thymine, quinazoline-2,4-dione, alloxazine) or to the C-5 and N-3 atoms of the 6-methyluracil moiety was synthesized. All compounds synthesized were evaluated for antiviral activity against influenza virus A/PR/8/34/(H1N1) and coxsackievirus B3. Antiviral assays revealed three compounds, 2i, 5i, 11c, which showed moderate activity against influenza virus A H1N1 with IC50 values of 57.5 µM, 24.3 µM, and 29.2 µM, respectively. In the first two nucleoside analogues, 1,2,3-triazol-4-yl-β-d-ribofuranosyl fragments are attached via butylene linkers to N-1 and N-3 atoms of the heterocycle moiety (6-methyluracil and alloxazine, respectively). In nucleoside analogue 11c, two 1,2,3-triazol-4-yl-2′,3′,5′-tri-O-acetyl-β-d-ribofuranose fragments are attached via propylene linkers to the C-5 and N-3 atoms of the 6-methyluracil moiety. Almost all synthesized 1,2,3-triazolyl nucleoside analogues showed no antiviral activity against the coxsackie B3 virus. Two exceptions are 1,2,3-triazolyl nucleoside analogs 2f and 5f, in which 1,2,3-triazol-4-yl-2′,3′,5′-tri-O-acetyl-β-d-ribofuranose fragments are attached to the C-5 and N-3 atoms of the heterocycle moiety (6-methyluracil and alloxazine respectively). These compounds exhibited high antiviral potency against the coxsackie B3 virus with IC50 values of 12.4 and 11.3 µM, respectively, although both were inactive against influenza virus A H1N1. According to theoretical calculations, the antiviral activity of the 1,2,3-triazolyl nucleoside analogues 2i, 5i, and 11c against the H1N1 (A/PR/8/34) influenza virus can be explained by their influence on the functioning of the polymerase acidic protein (PA) of RNA-dependent RNA polymerase (RdRp). As to the antiviral activity of nucleoside analogs 2f and 5f against coxsackievirus B3, it can be explained by their interaction with the coat proteins VP1 and VP2.

Antiviral Activity of Dopamine Geldanamycin Hybrids Against Influenza Virus and Association with Molecular Docking Analysis

2021 ◽  
Vol 17 (1) ◽  
pp. 1-14
Author(s):  
Thongchai Taechowisa ◽  
Tipparat Samsawat ◽  
Chanjira Jaramornbu ◽  
Weerachai Phutdhawon ◽  
Waya S. Phutdhawong Phutdhawon
Keyword(s):  
Influenza Virus ◽  
Molecular Docking ◽  
Antiviral Activity ◽  
Docking Analysis ◽  
Molecular Docking Analysis

scholarly journals Screening and Purification of NanB Sialidase From Pasteurella Multocida With Activity in Hydrolyzing Sialic Acid Neu5Acα(2-6)Gal

2021 ◽  
Author(s):  
Christian Marco Hadi Nugroho ◽  
Ryan Septa Kurnia ◽  
Simson Tarigan ◽  
Otto Sahat Martua Silaen ◽  
Silvia Tri Widyaningtyas ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Antiviral Activity ◽  
Red Blood Cells ◽  
Blood Cells ◽  
In Silico ◽  
Pasteurella Multocida ◽  
Antiviral Agents ◽  
Influenza Virus Infection ◽  
Ligand Complex ◽  
In Silico Studies

Abstract Study on sialidases as antiviral agents has been widely performed, but many types of sialidase had not been tested for their antiviral activity. One of such sialidase is the NanB sialidase of Pasteurella multocida, which has never been isolated for further study. In this study, the activity of NanB sialidase was investigated in silico by docking the NanB sialidase of Pasteurella multocida to the Neu5Acα(2-6)Gal ligand. Additionally, some local isolates of Pasteurella multocida, which had the NanB gene were screened, and the proteins were isolated for further testing regarding their activity in hydrolyzing Neu5Acα(2-6)Gal. In silico studies showed that the NanB sialidase possesses an exceptional affinity towards forming a protein-ligand complex with Neu5Acα(2-6)Gal. This was further confirmed by showing that a dose of 0.258 U/ml (100%) NanB sialidase of Pasteurella multocida B018 can hydrolyze up to 44.28% of Neu5Acα(2-6)Gal in chicken red blood cells and 81.95% in rabbit red blood cells. This study suggested that the NanB sialidase of Pasteurella multocida B018 has a potent antiviral activity that can inhibit avian influenza virus infection.

scholarly journals Screening and Purification of NanB Sialidase from Pasteurella Multocida with Activity in Hydrolyzing Sialic Acid Neu5Acα(2-6)Gal

2021 ◽  
Author(s):  
Christian Marco Hadi Nugroho ◽  
Ryan Septa Kurnia ◽  
Simson Tarigan ◽  
Otto Sahat Martua Silaen ◽  
Silvia Tri Widyaningtyas ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Antiviral Activity ◽  
Red Blood Cells ◽  
Blood Cells ◽  
In Silico ◽  
Pasteurella Multocida ◽  
Antiviral Agents ◽  
Influenza Virus Infection ◽  
Ligand Complex ◽  
In Silico Studies

Abstract Study on sialidases as antiviral agents has been widely performed, but many types of sialidase had not been tested for their antiviral activity. One of such sialidase is the NanB sialidase of Pasteurella multocida, which has never been isolated for further study. In this study, the activity of NanB sialidase was investigated in silico by docking the NanB sialidase of Pasteurella multocida to the Neu5Acα(2-6)Gal ligand. Additionally, some local isolates of Pasteurella multocida, which had the NanB gene were screened, and the proteins were isolated for further testing regarding their activity in hydrolyzing Neu5Acα(2-6)Gal. In silico studies showed that the NanB sialidase possesses an exceptional affinity towards forming a protein-ligand complex with Neu5Acα(2-6)Gal. This was further confirmed by showing that a dose of 0.258 U/ml (100%) NanB sialidase of Pasteurella multocida B018 can hydrolyze up to 44.28% of Neu5Acα(2-6)Gal in chicken red blood cells and 81.95% in rabbit red blood cells. This study suggested that the NanB sialidase of Pasteurella multocida B018 has a potent antiviral activity that can inhibit avian influenza virus infection.

scholarly journals Synthesis and Antiviral Activity of Camphene Derivatives against Different Types of Viruses

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2235
Author(s):  
Anastasiya S. Sokolova ◽  
Valentina P. Putilova ◽  
Olga I. Yarovaya ◽  
Anastasiya V. Zybkina ◽  
Ekaterina D. Mordvinova ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Antiviral Activity ◽  
Rational Design ◽  
Ebola Virus ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Surface Proteins ◽  
Hantaan Virus

To date, the ‘one bug-one drug’ approach to antiviral drug development cannot effectively respond to the constant threat posed by an increasing diversity of viruses causing outbreaks of viral infections that turn out to be pathogenic for humans. Evidently, there is an urgent need for new strategies to develop efficient antiviral agents with broad-spectrum activities. In this paper, we identified camphene derivatives that showed broad antiviral activities in vitro against a panel of enveloped pathogenic viruses, including influenza virus A/PR/8/34 (H1N1), Ebola virus (EBOV), and the Hantaan virus. The lead-compound 2a, with pyrrolidine cycle in its structure, displayed antiviral activity against influenza virus (IC50 = 45.3 µM), Ebola pseudotype viruses (IC50 = 0.12 µM), and authentic EBOV (IC50 = 18.3 µM), as well as against pseudoviruses with Hantaan virus Gn-Gc glycoprotein (IC50 = 9.1 µM). The results of antiviral activity studies using pseudotype viruses and molecular modeling suggest that surface proteins of the viruses required for the fusion process between viral and cellular membranes are the likely target of compound 2a. The key structural fragments responsible for efficient binding are the bicyclic natural framework and the nitrogen atom. These data encourage us to conduct further investigations using bicyclic monoterpenoids as a scaffold for the rational design of membrane-fusion targeting inhibitors.

scholarly journals Molecular Docking Studies and Biological Evaluation of Berberine–Benzothiazole Derivatives as an Anti-Influenza Agent via Blocking of Neuraminidase

2021 ◽  
Vol 22 (5) ◽  
pp. 2368
Author(s):  
Manu Kumar ◽  
Sang-Min Chung ◽  
Ganuskh Enkhtaivan ◽  
Rahul V. Patel ◽  
Han-Seung Shin ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Molecular Docking ◽  
Influenza A ◽  
Biological Properties ◽  
Biological Evaluation ◽  
Influenza B ◽  
Influenza A Viruses ◽  
Neuraminidase Activity ◽  
Benzothiazole Derivatives

In this study, we have introduced newly synthesized substituted benzothiazole based berberine derivatives that have been analyzed for their in vitro and in silico biological properties. The activity towards various kinds of influenza virus strains by employing the cytopathic effect (CPE) and sulforhodamine B (SRB) assay. Several berberine–benzothiazole derivatives (BBDs), such as BBD1, BBD3, BBD4, BBD5, BBD7, and BBD11, demonstrated interesting anti-influenza virus activity on influenza A viruses (A/PR/8/34, A/Vic/3/75) and influenza B viral (B/Lee/40, and B/Maryland/1/59) strain, respectively. Furthermore, by testing neuraminidase activity (NA) with the neuraminidase assay kit, it was identified that BBD7 has potent neuraminidase activity. The molecular docking analysis further suggests that the BBD1–BBD14 compounds’ antiviral activity may be because of interaction with residues of NA, and the same as in oseltamivir.

scholarly journals Chemical Characterization and Anti-HIV-1 Activity Assessment of Iridoids and Flavonols from Scrophularia trifoliata

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4777
Author(s):  
Francesca Guzzo ◽  
Rosita Russo ◽  
Cinzia Sanna ◽  
Odeta Celaj ◽  
Alessia Caredda ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Wide Spectrum ◽  
Iridoid Glycosides ◽  
Antiviral Agents ◽  
Chemical Characterization ◽  
Biological Properties ◽  
Rnase H ◽  
Chemical Structures ◽  
First Time ◽  
Hiv 1

Plants are the everlasting source of a wide spectrum of specialized metabolites, characterized by wide variability in term of chemical structures and different biological properties such antiviral activity. In the search for novel antiviral agents against Human Immunodeficiency Virus type 1 (HIV-1) from plants, the phytochemical investigation of Scrophularia trifoliata L. led us to isolate and characterize four flavonols glycosides along with nine iridoid glycosides, two of them, 5 and 13, described for the first time. In the present study, we investigated, for the first time, the contents of a methanol extract of S. trifoliata leaves, in order to explore the potential antiviral activity against HIV-1. The antiviral activity was evaluated in biochemical assays for the inhibition of HIV-1Reverse Transcriptase (RT)-associated Ribonuclease H (RNase H) activity and HIV-1 Integrase (IN). Three isolated flavonoids, rutin, kaempferol-7-O-rhamnosyl-3-O-glucopyranoside, and kaempferol-3-O-glucopyranoside, 8–10, inhibited specifically the HIV-1 IN activity at submicromolar concentration, with the latter being the most potent, showing an IC50 value of 24 nM.

Antiviral Activity of Extracts from the Daedaleopsis confragosa F-1368 Basidiomycete

2021 ◽  
Vol 37 (1) ◽  
pp. 21-25
Author(s):  
T.N. Ilyicheva ◽  
E.D. Danilenko ◽  
L.R. Lebedev
Keyword(s):  
Influenza Virus ◽  
Antiviral Activity ◽  
Pandemic Influenza ◽  
Culture Medium ◽  
Antiviral Agents ◽  
Hydrolytic Enzymes ◽  
Therapeutic Index ◽  
The State ◽  
Influenza Virus A ◽  
State Assignment

The antiviral activity of extracts of the basidial fungus Daedaleopsis confragosa (Bolton) J. Schröt strain F-1368 cultivated under the laboratory conditions has been studied. It was shown that the extracts obtained from 1 L of the culture contained proteins and polysaccharides in the amount of 71±5 and 413±15 mg/L of culture, respectively. Antiviral activity (ED50) against the pandemic influenza virus A/California/07/09 (H1N1)pdm09 was observed at extract concentrations in the range of 0.02-0.12 mg/mL depending on the culture medium. The therapeutic index (CC50/ED50) was at the level of 14-17, which makes it possible to recommend D. confragosa extracts for the development of antiviral agents. It was shown that treatment with hydrolytic enzymes (trypsin, zymolyase) leads to an increase in cytotoxicity and a decrease in the antiviral activity of the extracts. Daedaleopsis confragosa, basidomycetes, extracts, antiviral activity, influenza virus The study was carried out according to the state assignment to FBRI SRC VB «Vector», Rospotrebnadzor, Koltsovo.

Natural antimicrobial peptides as a source of new antiviral agents

2021 ◽  
Vol 102 (9) ◽  
Author(s):  
Hovakim Zakaryan ◽  
Garri Chilingaryan ◽  
Erik Arabyan ◽  
Andre Serobian ◽  
Guangshun Wang
Keyword(s):  
Antiviral Activity ◽  
Antimicrobial Peptides ◽  
Antiviral Agents ◽  
Chemical Properties ◽  
Biological Properties ◽  
Emerging Viruses ◽  
Adverse Side Effects ◽  
Physical Chemical ◽  
Therapeutic Properties ◽  
New Generation

Current antiviral drugs are limited because of their adverse side effects and increased rate of resistance. In recent decades, much scientific effort has been invested in the discovery of new synthetic and natural compounds with promising antiviral properties. Among this new generation of compounds, antimicrobial peptides with antiviral activity have been described and are attracting attention due to their mechanism of action and biological properties. To understand the potential of antiviral peptides (AVPs), we analyse the antiviral activity of well-known AVP families isolated from different natural sources, discuss their physical–chemical properties, and demonstrate how AVP databases can guide us to design synthetic AVPs with better therapeutic properties. All considerations in this sphere of antiviral therapy clearly demonstrate the remarkable contribution that AVPs may make in conquering old as well as newly emerging viruses that plague humanity.

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