Inhibitory Effect of Abitylguanide on Adenovirus Replication

Drug Research ◽  
2017 ◽  
Vol 67 (10) ◽  
pp. 583-590 ◽  
Author(s):  
Angel Galabov ◽  
Vesselina Vassileva ◽  
Vera Karabasheva

AbstractN’N’-anhydro-bis(β-hydroxy-ethyl)biguanide.HCl (abitylguanide) demonstrated a marked inhibitory effect on replication in cell cultures of a broad spectrum of human adenoviruses both standard laboratory strains and strains isolated from epidemic keratoconjunctivitis patients. The strongest inhibitory activity was found in viruses belonging to subgroup C (Rosen’s subgroup III). The compound susceptible period of human adenovirus 5 replication in primary cell cultures of human embryo kidney cells included the total replication cycle and was especially pronounced during the exponential phase of the virus growth curve. Electron microscopy established that the compound decreased the percentage of cells in which mature or empty virions with the characteristic nuclear localization were observed; a complete absence of paracrystals was registered and the number of cells with virus particles arranged in crystals in the nucleoplasm was strongly decreased. Abitylguanide can be considered as a ligand of adenovirus capsid protein(s).

1996 ◽  
Vol 51 (7-8) ◽  
pp. 558-562 ◽  
Author(s):  
Angel S. Galabov ◽  
Tanya Iosifova ◽  
Elka Vassileva ◽  
Ivanka Kostova

Abstract Esculetin (6,7-dihydroxycoumarin) and its diacetate exhibited a marked inhibitory effect on Newcastle disease virus replication in cell cultures at concentrations of 36 jam and 62 jam, respectively. These compounds were selected from ten hydroxycoumarin derivatives through an in vitro antiviral screen involving viruses of the picorna-, orthomyxo-, paramyxo-, and herpes virus families.


1970 ◽  
Vol 68 (1) ◽  
pp. 151-158 ◽  
Author(s):  
R. D. Barry ◽  
Patricia Davies

SummaryThe isoquinoline compound UK 2054 prevents the uptake of influenza virus by susceptible cells. Pre-incubation of virus particles with 500μg./ml. UK 2054 at 37°C. for 2 hr. does not reduce virus infectivity. Host cells vary in their responsiveness to the inhibitory effect of UK 2054; virus multiplication is inhibited in chick allantoic cells by lower concentrations than those required to inhibit virus growth in chick embryo fibroblasts. The effectiveness of UK 2054 is reduced by the presence of serum.It is concluded that inhibition of influenza virus multiplication by UK2054 might result from interaction of the inhibitor with both virus and cells. Any direct combination between inhibitor and virus is completely reversible.


2020 ◽  
Author(s):  
Emil Johansson ◽  
Rémi Caraballo ◽  
Nitesh Mistry ◽  
Georg Zocher ◽  
Weixing Qian ◽  
...  

Coxsackievirus A24 variant (CVA24v) and human adenovirus 37 (HAdV-37) are leading causative agents of the severe and highly contagious ocular infections acute hemorrhagic conjunctivitis and epidemic keratoconjunctivitis, respectively. Currently, neither vaccines nor antiviral agents are available for treating these diseases, which affect millions of individuals worldwide. CVA24v and HAdV-37 utilize sialic acid as attachment receptors facilitating entry into host cells. Previously, we and others have shown that derivatives based on sialic acid are effective in preventing HAdV-37 binding and infection of cells. Here, we designed and synthesized novel pentavalent sialic acid conjugates and studied their inhibitory effect against CVA24v and HAdV-37 binding and infection of human corneal epithelial cells. The pentavalent conjugates are the first reported inhibitors of CVA24v infection, and proved efficient in blocking HAdV-37 binding. Taken together, the pentavalent conjugates presented here form a basis for the development of general inhibitors of these highly contagious ocular pathogens.


2020 ◽  
Author(s):  
Emil Johansson ◽  
Rémi Caraballo ◽  
Nitesh Mistry ◽  
Georg Zocher ◽  
Weixing Qian ◽  
...  

Coxsackievirus A24 variant (CVA24v) and human adenovirus 37 (HAdV-37) are leading causative agents of the severe and highly contagious ocular infections acute hemorrhagic conjunctivitis and epidemic keratoconjunctivitis, respectively. Currently, neither vaccines nor antiviral agents are available for treating these diseases, which affect millions of individuals worldwide. CVA24v and HAdV-37 utilize sialic acid as attachment receptors facilitating entry into host cells. Previously, we and others have shown that derivatives based on sialic acid are effective in preventing HAdV-37 binding and infection of cells. Here, we designed and synthesized novel pentavalent sialic acid conjugates and studied their inhibitory effect against CVA24v and HAdV-37 binding and infection of human corneal epithelial cells. The pentavalent conjugates are the first reported inhibitors of CVA24v infection, and proved efficient in blocking HAdV-37 binding. Taken together, the pentavalent conjugates presented here form a basis for the development of general inhibitors of these highly contagious ocular pathogens.


Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1142
Author(s):  
Tsuyoshi Ando ◽  
Takeshi Nabeshima ◽  
Shingo Inoue ◽  
Mya Myat Ngwe Tun ◽  
Miho Obata ◽  
...  

In this study, we investigated severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) infection in cats in Nagasaki, Japan. In total, 44 of 133 (33.1%) cats with suspected SFTS were confirmed to be infected with SFTSV. Phylogenetic analyses of SFTSV isolates from cats indicated that the main genotype in Nagasaki was J1 and that unique reassortant strains with J2 (S segment) and unclassified genotypes (M and L segments) were also present. There were no significant differences in virus growth in cell cultures or fatality in SFTSV-infected mice between the SFTSV strains that were isolated from recovered and fatal cat cases. Remarkably, SFTSV RNAs were detected in the swabs from cats, indicating that the body fluids contain SFTSV. To evaluate the risk of SFTSV infection when providing animal care, we further examined the seroprevalence of SFTSV infection in veterinarian staff members; 3 of 71 (4.2%) were seropositive for SFTSV-specific antibodies. Our results provide useful information on the possibility of using cats as sentinel animals and raised concerns of the zoonotic risk of catching SFTSV from animals.


2002 ◽  
Vol 50 (4) ◽  
pp. 481-489 ◽  
Author(s):  
Cs. Jeney ◽  
Boglárka Banizs ◽  
Orsolya Dobay ◽  

The effects of bafilomycin A1 and of the reduced level of endosomal epsilon-COP (coatomer protein) on the infectivity of human adenovirus type 5 were investigated in Coxsackie adenovirus receptor- (CAR-) transfected Chinese hamster ovary (CHO) cells. The endosomal proton pump inhibitor bafilomycin A1 was able to cause only partial inhibition. Using ldlF cells (an epsilon-COP thermosensitive mutant CHO cell line) the reduction of epsilon-COP level also had partial inhibitory effect. Based on these results and comparing them to existing models of the adenovirus entry, we propose a refined model in which there are two pathways of adenoviral entry: the first one involves the epsilon-COP as the downstream effector of the acidification and can be blocked by bafilomycin A1 and the second one is a pH-independent pathway.


1986 ◽  
Vol 164 (5) ◽  
pp. 1407-1421 ◽  
Author(s):  
J E Gabay ◽  
J M Heiple ◽  
Z A Cohn ◽  
C F Nathan

We examined the subcellular location of bactericidal factors (BF) in human neutrophils, using an efficient fractionation scheme. Nitrogen bomb cavitates of DIFP-treated PMN were centrifuged through discontinuous Percoll gradients, each fraction extracted with 0.05 M glycine, pH 2.0, and tested for the killing of Escherichia coli. greater than 90% of BF coisolated with the azurophil granules. After lysis of azurophils, 98% of azurophil-derived BF (ADBF) sedimented with the membrane. ADBF activity was solubilized from azurophil membrane with either acid or nonionic detergent (Triton X-100, Triton X-114). Bactericidal activity was linear with respect to protein concentration over the range 0.3-30 micrograms/ml. 0.1-0.3 microgram/ml ADBF killed 10(5) E. coli within 30 min at 37 degrees C. At 1.4 micrograms/ml, 50% of 2 X 10(5) bacteria were killed within 5 min. ADBF was effective between pH 5-8, with peak activity at pH 5.5. Glucose (20 mM), EDTA (1-25 mM), and physiologic concentrations of NaCl or KCl had little or no inhibitory effect on ADBF. ADBF killed both Gram-positive and Gram-negative virulent clinical isolates, including listeria, staphylococci, beta-hemolytic streptococci, and Pseudomonas aeruginosa. Thus, under these conditions of cell disruption, fractionation, extraction, and assay, almost all BF in human PMN appeared to be localized to the membrane of azurophilic granules as a highly potent, broad-spectrum, rapidly acting protein(s) effective in physiologic medium. Some of these properties appear to distinguish ADBF from previously described PMN bactericidal proteins.


1974 ◽  
Vol 15 (2) ◽  
pp. 407-417
Author(s):  
J. B. GRIFFITHS

The object was to determine whether the depletion of histidine would have a more marked inhibitory effect on human leukaemia cells than on normal human cells, thus indicating a wider use for enzymes in cancer therapy. Studies of the effect of histidine concentration on cell growth, death, metabolism, protein composition, histidine uptake and utilization by cells were carried out. The medium and intracellular concentrations of histidine required for optimum cell growth and metabolism were much lower than for any other amino acid that has been studied. Also, there was very little evidence of cell death occurring in the absence of histidine. The results showed that cells in culture have a very low histidine requirement and that although the leukaemia cells were slightly more dependent upon histidine than normal cells the effect of histidine depletion is not critical enough to show much promise as a method of controlling leukaemia by therapeutic enzymes.


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