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C Gil-Fernández

Publications and source records attributed to C Gil-Fernández.

16 recordsLinked to original sources
PubMed1993

Activity of several S-adenosylhomocysteine hydrolase inhibitors against African swine fever virus replication in Vero cells.

Several inhibitors of S-adenosylhomocysteine (AdoHcy) hydrolase have been found to selectively suppress the replication of African swine fever virus (ASFV) in Vero cells. Of the compounds tested, 3-deazaneplanocin A proved to be the most potent and selective inhibitor of ASFV replication. Its selectivity index (SI) was 3000. Then followed 9-(trans-2',trans-3'-dihydroxycyclopentyl)-3- deazaadenine (SI = 2500), the 4'beta-vinyl derivative of 9-(trans-2',trans-3'-dihydroxycyclopentyl)adenine (SI = 2000), 6'beta-fluoroaristeromycin (SI = 1250), 4',5'-unsaturated 5'-fluoroadenosine (MDL 28842) and 9-(trans-2',trans-3'-dihydroxycyclopentyl)adenine (SI = 667), 9-(trans-2',trans-3'-dihydroxycyclopent-4'-enyl)adenine and the 4 beta-methyl derivative of 9-(trans-2',trans-3'- dihydroxycyclopentyl)adenine (SI = 400), 9-(trans-2',trans-3'-dihydroxycyclopent-4'-enyl)-3-deazaadenine (SI = 200). We postulate that the mechanism of anti-ASFV action of these compounds is based on the inhibition of AdoHcy hydrolase, thus resulting in the accumulation of AdoHcy and suppression of methylation reactions needed for viral mRNA maturation.

Adenosylhomocysteinase↗
PubMed1991

Antiviral activity of sulfated polysaccharides against African swine fever virus.

The polyanionic substances lambda and kappa carrageenan, pentosan polysulfate, fucoidan, dextran sulfate and heparin were investigated for their inhibitory effect on the replication of African swine fever virus (ASFV) in vitro. Lambda carrageenan was the most efficacious with a selectivity index, as based on the ratio of the 50% cytotoxic concentration to the 50% antiviral effective concentration, of 120, followed by pentosan polysulfate with 30, kappa carrageenan 13.3 and fucoidan 10. Dextran sulfate and heparin were almost inactive. In general, the substances had low toxicity for Vero cells. The studies with radiolabeled ASF virions suggest that the sulfated polysaccharides inhibit virus adsorption. Inhibition of virus replication was found for all the polysaccharides only when the substances were present during virus adsorption, with the exception of lambda and kappa carrageenan, which were also inhibitory when added immediately after the adsorption period.

Adsorption↗
PubMed1988

Inhibition of African swine fever virus DNA synthesis by (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine.

The acyclic nucleotide analogue (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA] is a potent and selective inhibitor of African swine fever virus (ASFV) replication. Using the DNA-DNA hybridization technique with plasmid pRPEL-2 as probe, we have shown that (S)-HPMPA exerts a specific, dose-dependent, inhibitory effect on viral DNA synthesis. Also, (S)-HPMPA inhibits the production of late viral proteins, especially IP-73, in ASFV-infected MS and Vero cells. When evaluated under the same experimental conditions, phosphonoacetic acid (PAA) also caused an inhibition of viral DNA and late viral protein synthesis but only so at a concentration which was 10- to 20-fold higher than that required for (S)-HPMPA.

Adenine↗
PubMed1988

A model virus-cell system to study the persistence of African swine fever virus.

The persistence of African swine fever virus (ASFV) on Vero cells was induced by using 5-iodo-2'-deoxyuridine (IDU). After the persistence was established, several cycles of decreasing virus production were observed with intervals in which no virus could be detected. These latency-like periods could last from 15 to 25 days. After three and a half months the cells appeared to be "cured" and no virus was detected during almost three years. These "cured" cells (Vero-L) were more resistant to superinfection with the wild type virus, and when infected they always established persistence without drug addition characterized by a continuous virus production. The persistent virus isolated at passage 23rd from ASFV persistently infected Vero-L cells was different from wild type in a) the morphology of the plaque, b) its ability to replicate in Vero-L cells, and c) greater resistance to be inhibited by IDU in normal Vero cells (Vero-N). These results suggest that both, Vero cells and ASFV have changed during persistent infection.

African Swine Fever Virus↗
PubMed1987

Comparative efficacy of broad-spectrum antiviral agents as inhibitors of African swine fever virus replication in vitro.

Various nucleoside analogues, selected on the basis of their previously established broad-spectrum antiviral properties, were evaluated for their potency and selectivity as inhibitors of the in vitro replication of the iridovirus, African swine fever virus (ASFV). The test compounds included (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], 9-(2-phosphonylmethoxyethyl)adenine, (RS)-3-adenin-9-yl-2-hydroxypropanoic acid isobutyl ester, (S)-9-(2,3-dihydroxypropyl)adenine, carbocyclic 3-deazaadenosine (C-c3Ado), 3'-azido-2',3'-dideoxythymidine, pyrazofurin and ribavirin. As the most efficacious inhibitors of ASFV replication emerged (S)-HPMPA followed by C-c3Ado. The minimum inhibitory concentration of (S)-HPMPA for ASFV replication was 0.01 microgram/ml, and its selectivity index was 15,000. The corresponding values for C-c3Ado were 0.025 micrograms/ml and 8000, respectively. It would seem justified to further pursue these compounds for their anti ASFV activity in vivo.

Adenine↗
PubMed1987

Phosphonylmethoxyalkylpurines and -pyrimidines as inhibitors of African swine fever virus replication in vitro.

Several phosphonylmethoxyalkylpurine and -pyrimidine derivatives related to (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA] and 9-(2-phosphonylmethoxyethyl)adenine (PMEA) were evaluated as inhibitors of African swine fever virus (ASFV) replication in Vero cells. (S)-HPMPA has previously been shown to inhibit ASFV replication at a minimum inhibitory concentration (MIC) of 0.01 microgram/ml with a selectivity index of 15000. Of the new compounds tested, the following emerged as the most potent and selective inhibitors of ASFV replication: the cyclic phosphonate of (S)-HPMPA [(S)-cHPMPA] with an MIC of 0.2 microgram/ml and a selectivity index of 2500, the 2,6-diaminopurine analogue of (S)-HPMPA [(S)-HPMPDAP] with an MIC of 0.5 microgram/ml and a selectivity index of 1400, and the cytosine [(S)-HPMPC] and guanine [(RS)-HPMPG] analogues with an MIC of 1 microgram/ml and a selectivity index of 600-700.

African Swine Fever Virus↗
PubMed1986

New agents active against African swine fever virus.

Actinobolin, atropine, carrageenan, megalomycin C, suramin, and tetracenomycin C were tested for their activity against African swine fever virus replication. Both viral inhibitory potency and cytotoxicity were investigated. Megalomycin C, suramin, atropine, and carrageenan exhibited significant activity. Megalomycin C was the most active of the four agents with respect to the concentration of compound that blocked the formation of infectious virus by 50%. Suramin was the next most active agent in this respect, but because of its lower cytotoxicity, it had the most favorable therapeutic index.

African Swine Fever Virus↗
PubMed1984

Antiviral action of 5-amino-2-(2-dimethyl-aminoethyl)benzo-[de]-isoquinolin-1,3-dion e.

A newly synthesized imide derivative of 3-nitro-1,8-naphthalic acid, 5-amino-2-(2-dimethylaminoethyl)benzo-[de]-isoquinolin-1,3-dione (designated M-FA-142), was tested on chick embryo cells against herpes simplex virus type 1 (HSV-1) and vaccinia virus (VV), and on Vero cells against African swine fever virus (ASFV). At a concentration of 4 micrograms/ml the drug inhibited VV replication by about one order of magnitude, and that of HSV-1 by about three orders of magnitude. A minor effect was shown against ASFV. Virus inhibition was found to depend on the amount of drug and multiplicity of infection. No virucidal effect was observed on the viruses tested, except for a slight effect on HSV-1. Inhibition of virus growth could be reversed when the drug was removed from the cell culture medium. Serial passages of HSV-1 and VV in the presence of the drug caused the appearance of drug-resistant viruses.

Adenine↗
PubMed1982

Imide derivatives of 3-nitro-1.8-naphthalic acid: their inhibitory activity against DNA viruses.

The antiviral action of a new drug, 5-amino-2-(dimethylaminoethyl)-benzo-[de]-isoquinolin-1.3-dione has been studied against herpes simplex type 2 (HSV-2) and adenovirus type 5 (Ad-5) grown in Vero cells. The concentration of the drug which gives a 5 log10 reduction in virus titer was 4 micrograms/ml (maximum tolerated concentration) for HSV-2. The anti-HSV-2 activity of this compound was one log. more powerful than that of iododeoxyuridine (IDU). At this concentration the drug shows virucidal activity against HSV-2. No inhibition was found when the drug was tested against Ad-5. The inhibition of virus production has been studied depending upon the amount of drug or virus, and drug addition-time after infection. Reversibility of inhibition after drug removal, and drug resistance in the presence of the drug have also been determined.

Adenine↗
PubMed1979

Effect of disodium phosphonoacetate and iododeoxyuridine on the multiplication of African swine fever virus in vitro.

Disodium phosphonoacetate (PAA) was found to inhibit the replication of African swine fever virus (ASFV). The action of this compound has been compared with the inhibitory capacity of iododeoxyuridine (IDU) upon ASFV growing in Vero cells. The study was done by the immunofluorescence technique in order to detect formations of cytoplasmic virus antigens and inclusion bodies; both were found to be inhibited by IDU and PAA. At 100 microgram/ml, IDU blocked completely the multiplication of ASFV and with PAA, a few scattered cells showed positive fluorescence. The infectivity of the virus was reduced 1--5 log depending upon drug concentrations and time of exposure to the drugs. Inhibition of ASFV replication by PAA suggests that this virus, like other herpesviruses, involves a virus-specific DNA polymerase in its replication mechanism.

African Swine Fever Virus↗