title: Echinhibin-1--an inhibitor of Sendai virus isolated from the venom of the snake Echis coloratus.
abstract: 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.
authors.affiliation: Department of Zoology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Borkow
authors.forename: M
authors.initials: M
authors.lastname: Ovadia
mesh_terms: 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
chemical_list: D000998:Antiviral Agents; D006023:Glycoproteins; D012910:Snake Venoms; D014757:Viper Venoms; C086565:echinhibin-1 protein, Echis coloratus; D008666:Metalloendopeptidases