Inhibitory effects of 3-imino-5-phenyl-3H-1,2-dithiole on poliovirus type 1 replication in vitro

1990 ◽  
Vol 14 (4-5) ◽  
pp. 267-277 ◽  
Author(s):  
A. Garozzo ◽  
M.R. Pinizzotto ◽  
P.M. Furneri ◽  
D. Baratta ◽  
F. Guerrera ◽  
...  
Keyword(s):  
Inhibitory Effects ◽  
Poliovirus Type

scholarly journals Biochemical and Genetic Studies of the Initiation of Human Rhinovirus 2 RNA Replication: Identification of a cis-Replicating Element in the Coding Sequence of 2Apro

2001 ◽  
Vol 75 (22) ◽  
pp. 10979-10990 ◽  
Author(s):  
Kinga Gerber ◽  
Eckard Wimmer ◽  
Aniko V. Paul
Keyword(s):  
Rna Replication ◽  
Human Rhinovirus ◽  
Viral Sequence ◽  
Coding Region ◽  
Terminal Protein ◽  
Genetic Studies ◽  
Poliovirus Type ◽  
Coding Sequence

ABSTRACT We have previously shown that the RNA polymerase 3Dpolof human rhinovirus 2 (HRV2) catalyzes the covalent linkage of UMP to the terminal protein (VPg) using poly(A) as a template (K. Gerber, E. Wimmer, and A. V. Paul, J. Virol. 75:10969–10978, 2001). The products of this in vitro reaction are VPgpU, VPgpUpU, and VPg-poly(U), the 5′ end of minus-strand RNA. In the present study we used an assay system developed for poliovirus 3Dpol (A. V. Paul, E. Rieder, D. W. Kim, J. H. van Boom, and E. Wimmer, J. Virol. 74: 10359–10370, 2000) to search for a viral sequence or structure in HRV2 RNA that would provide specificity to this reaction. We now show that a small hairpin in HRV2 RNA [cre(2A)], located in the coding sequence of 2Apro, serves as the primary template for HRV2 3Dpol in the uridylylation of HRV2 VPg, yielding VPgpU and VPgpUpU. The in vitro reaction is strongly stimulated by the addition of purified HRV2 3CDpro. Our analyses suggest that HRV2 3Dpol uses a “slide-back” mechanism during synthesis of the VPg-linked precursors. The corresponding cis- replicating RNA elements in the 2CATPase coding region of poliovirus type 1 Mahoney (I. Goodfellow, Y. Chaudhry, A. Richardson, J. Meredith, J. W. Almond, W. Barclay, and D. J. Evans, J. Virol. 74:4590–4600, 2000) and VP1 of HRV14 (K. L. McKnight and S. M. Lemon, RNA 4:1569–1584, 1998) can be functionally exchanged in the assay with cre(2A) of HRV2. Mutations of either the first or the second A in the conserved A1A2A3CA sequence in the loop of HRV2 cre(2A) abolished both viral growth and the RNA's ability to serve as a template in the in vitro VPg uridylylation reaction.

Selective inhibitory effects of hybrid liposomes on the growth of HIV type 1-infected cells in vitro

2008 ◽  
Vol 18 (16) ◽  
pp. 4578-4580 ◽  
Author(s):  
Ryuichi Ueoka ◽  
Yuji Komizu ◽  
Yoko Matsumoto ◽  
Yu Zhong ◽  
Ritsuko Tanaka ◽  
...  
Keyword(s):  
Inhibitory Effects ◽  
Infected Cells ◽  
Hiv Type 1

Ein chromatographisches Verfahren zur Bestimmung typenspezifischer Poliovirus-Antikörper mit 32P-markiertem Polioviru

1963 ◽  
Vol 18 (10) ◽  
pp. 798-808 ◽  
Author(s):  
Reiner Thomssen
Keyword(s):  
Aluminium Hydroxide ◽  
Virus Antibody ◽  
Poliovirus Type ◽  
Specific Antibodies ◽  
In Vitro Technique ◽  
Step Procedure ◽  
Highly Sensitive

A highly sensitive in-vitro technique for determination of homologous type-specific antibodies against polioviruses is described. 32P-labelled poliovirus type 1. strain Mahoney, purified by a three-step-procedure (15 000 rpm, aluminiumhydroxide. Ecteolacellulose) is mixed with homologous type-specific antiserum. After incubation the mixtures are adsorbed to aluminium hydroxide. Virus-antibody-com-plexes are more firmly bound to this adsorbent than virus without antibody: the distinguishing parameter is the concentration of divalent phosphate in the adsorption or the elution fluid. The firmness of binding of virus-antibody-complexes to aluminium hydroxide is further a function of the dilution of antiserum. This leads to a suitable end-point for reading antiserum titers. There is a good correlation between titers determined by this method and titers, determined by common neutralization tests. The method may be used to judge the virus-specifity of radioactivity after purification of 32P-labelled poliovirus.

scholarly journals Genetic and Biochemical Studies of Polioviruscis-Acting Replication Element cre in Relation to VPg Uridylylation

2000 ◽  
Vol 74 (22) ◽  
pp. 10371-10380 ◽  
Author(s):  
Elizabeth Rieder ◽  
Aniko V. Paul ◽  
Dong Wook Kim ◽  
Jacques H. van Boom ◽  
Eckard Wimmer
Keyword(s):  
Genome Replication ◽  
Coding Region ◽  
Stem Loop ◽  
Genetic Changes ◽  
Poliovirus Type ◽  
Type 3 ◽  
Type Sequence

ABSTRACT In addition to highly conserved stem-loop structures located in the 5′- and 3′-nontranslated regions, genome replication of picornaviruses requires cis-acting RNA elements located in the coding region (termed cre) (K. L. McKnight and S. M. Lemon, J. Virol. 70:1941–1952, 1996; P. E. Lobert, N. Escriou, J. Ruelle, and T. Michiels, Proc. Natl. Acad. Sci. USA 96:11560–11565, 1999; I. Goodfellow, Y. Chaudhry, A. Richardson, J. Meredith, J. W. Almond, W. Barclay, and D. J. Evans, J. Virol. 74:4590–4600, 2000). cre elements appear to be essential for minus-strand RNA synthesis by an as-yet-unknown mechanism. We have discovered that the cre element of poliovirus (mapping to the 2C coding region of poliovirus type 1; nucleotides 4444 to 4505 in 2C), which is homologous to thecre element of poliovirus type 3, is preferentially used as a template for the in vitro uridylylation of VPg catalyzed by 3Dpol in a reaction that is greatly stimulated by 3CDpro (A. V. Paul, E. Rieder, D. W. Kim, J. H. van Boom, and E. Wimmer, J. Virol. 74:10359–10370, 2000). Here we report a direct correlation between mutations that eliminate, or severely reduce, the in vitro VPg-uridylylation reaction and produce replication phenotypes in vivo. None of the genetic changes significantly influenced translation or polyprotein processing. A substitution mapping to the first A (A4472C) of a conservedAAACA sequence in the loop of PV-cre(2C) eliminated the ability of the cre RNA to serve as template for VPg uridylylation and abolished RNA infectivity. Mutagenesis of the second A (A4473C; AAACA) severely reduced the yield of VPgpUpU and RNA infectivity was restored only after reversion to the wild-type sequence. The effect of substitution of the third A (A4474G; AAACA) was less severe but reduced both VPg uridylylation and virus yield. Disruption of base pairing within the upper stem region of PV-cre(2C) also affected uridylylation of VPg. Virus derived from transcripts containing mutations in the stem was either viable or quasi-infectious.

In vitro antiviral activity of four isothiazole derivatives against poliovirus type 1

1992 ◽  
Vol 19 (1) ◽  
pp. 29-41 ◽  
Author(s):  
M.R. Pinizzotto ◽  
A. Garozzo ◽  
F. Guerrera ◽  
A. Castro ◽  
M.G. La Rosa ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Poliovirus Type

scholarly journals Synthesis of novel 13α-estrone derivatives by Sonogashira coupling as potential 17β-HSD1 inhibitors

2017 ◽  
Vol 13 ◽  
pp. 1303-1309 ◽  
Author(s):  
Ildikó Bacsa ◽  
Rebeka Jójárt ◽  
János Wölfling ◽  
Gyula Schneider ◽  
Bianka Edina Herman ◽  
...  
Keyword(s):  
Methyl Ether ◽  
Hydroxysteroid Dehydrogenase ◽  
Coupling Reactions ◽  
Sonogashira Coupling ◽  
Partial Saturation ◽  
Inhibitory Effects ◽  
Microwave Reactor ◽  
Incubation Method

Novel 13α-estrone derivatives were synthesized by Sonogashira coupling. Transformations of 2- or 4-iodo regioisomers of 13α-estrone and its 3-methyl ether were carried out under different conditions in a microwave reactor. The 2-iodo isomers were reacted with para-substituted phenylacetylenes using Pd(PPh3)4 as catalyst and CuI as a cocatalyst. Coupling reactions of 4-iodo derivatives could be achieved by changing the catalyst to Pd(PPh3)2Cl2. The product phenethynyl derivatives were partially or fully saturated. Compounds bearing a phenolic OH group furnished benzofurans under the conditions used for the partial saturation. The inhibitory effects of the compounds on human placental 17β-hydroxysteroid dehydrogenase type 1 isozyme (17β-HSD1) were investigated by an in vitro radiosubstrate incubation method. Certain 3-hydroxy-2-phenethynyl or -phenethyl derivatives proved to be potent 17β-HSD1 inhibitors, displaying submicromolar IC50 values.

scholarly journals Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors

2018 ◽  
Vol 14 ◽  
pp. 2838-2845 ◽  
Author(s):  
Rebeka Jójárt ◽  
Szabolcs Pécsy ◽  
György Keglevich ◽  
Mihály Szécsi ◽  
Réka Rigó ◽  
...  
Keyword(s):  
Organic Anion ◽  
Microwave Assisted Synthesis ◽  
Diethyl Phosphite ◽  
Steroid Sulfatase ◽  
Inhibitory Effects ◽  
Organic Anion Transporting Polypeptide ◽  
Structure Activity ◽  
New Compounds

Novel 2- or 4-phosphonated 13α-estrone derivatives were synthesized via the Hirao reaction. Bromo regioisomers (2- or 4-) of 13α-estrone and its 3-benzyl or 3-methyl ether were reacted with diethyl phosphite or diphenylphosphine oxide using Pd(PPh3)4 as catalyst under microwave irradiation. The influence of the new compounds on the transport function of the organic anion transporting polypeptide OATP2B1 was investigated by measuring Cascade Blue uptake. Derivatives bearing a 3-benzyl ether function displayed substantial submicromolar OATP2B1 inhibitory activity. The inhibitory effects of the compounds on human placental steroid sulfatase (STS) and 17β-hydroxysteroid dehydrogenase type 1 isozyme (17β-HSD1) were investigated by in vitro radiosubstrate incubation methods. None of the test compounds inhibited the STS markedly. The structure–activity relationship evaluation revealed that 2-substituted 3-hydroxy derivatives are able to inhibit the 17β-HSD1 enzyme with submicromolar IC50 values. Dual OATP2B1 and 17β-HSD1 inhibitors have been identified.

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