Echinhibin-1--an inhibitor of Sendai virus isolated from the venom of the snake Echis coloratus.
The snake venom of Echis coloratus was found to abolish the hemagglutinating activity, hemolytic activity and in vivo infectivity of Sendai virus. The active factor (Echinhibin-1) was purified by gel filtration on Sephadex G-50, followed by chromatography on DEAE-Sepharose and CM-Sepharose. Echinhibin-1 is a protease with a molecular weight of about 25 kDa, an isoelectric point of 7 and is stained by PAS, indicating that it is a glycoprotein. It showed a strong azocollase activity that was stable up to 68 degrees C and at pH values of 4.5-10.5. Ten micrograms/ml were sufficient to abolish the hemolytic effect of the virus on human erythrocytes when incubation was at 37 degrees C for 2 h, while 20 micrograms/ml abolished the hemagglutinating activity. Addition of Echinhibin-1 after the adsorption of Sendai virions onto washed erythrocytes at 4 degrees C did not inhibit the subsequently hemolytic activity at 37 degrees C, indicating that Echinhibin-1 interferes with virus adsorption to the cells. Of various protease inhibitors, only Na2 EDTA and o-phenanthroline inhibited the antiviral activity of the purified factor, indicating that it is a metalloproteinase. In vivo, mice inoculated intranasally with the virus pretreated with Echinhibin-1 developed well and gained weight, whereas untreated virus-infected mice lost weight and died within 1 week. Intravenous administrations of the purified factor up to 80 micrograms/mouse produced no signs of toxicity and subcutaneous injections caused no hemorrhagic activity, while the whole venom is very hemorrhagic with an LD50 of 250 micrograms/kg for mice.
Borkow
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G
Department of Zoology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Israel.
Ovadia
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D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology / Q000633:toxicity; D002847:Chromatography, Agarose; D006023:Glycoproteins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology / Q000633:toxicity; D006387:Hemagglutination, Viral / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D007526:Isoelectric Point; D007928:Lethal Dose 50; D008666:Metalloendopeptidases / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology / Q000633:toxicity; D051379:Mice; D008813:Mice, Inbred ICR; D008970:Molecular Weight; D010222:Parainfluenza Virus 1, Human / Q000187:drug effects*; D012867:Skin / Q000473:pathology; D012910:Snake Venoms; D014757:Viper Venoms / Q000737:chemistry* / Q000494:pharmacology
D000998:Antiviral Agents; D006023:Glycoproteins; D012910:Snake Venoms; D014757:Viper Venoms; C086565:echinhibin-1 protein, Echis coloratus; D008666:Metalloendopeptidases