Screening for fibrinolytic activity in eight Viperid venoms

Snake venoms contain direct-acting fibrinolytic metalloproteinases (MMP) th at could have important applications in medicine. Fibrinolytic enzymes isol ated from venom can induce in vitro clot lysis by directly acting on a fibr in clot. The most ideal fibrinolytic enzyme would have high affinity for cl ots, dissolve clots directly without causing hemorrhage, and would not be n eutralized in vivo by endogenous metalloproteinase inhibitors. The purpose of this study was to compare DEAE/HPLC venom profiles from Viperid snakes a nd identify fractions that contain fibrinolytic activity with no hemorrhagi c activity and are not neutralized by animal sera. The sera selected were f rom four (Virginia opossum, Gray woodrat, Mexican ground squirrel, and Hisp id cottonrat) animals known to neutralize hemorrhagic activity in snake ven oms. Nineteen fractions from the Viperid venoms had fibrinolytic activity. Agkistrodon venom fractions contained the highest specific fibrinolytic act ivities. A. piscivorus leucostoma fraction 4 contained a high specific fibr inolytic activity, no hemorrhagic activity, and the fibrinolytic activity w as not neutralized by the proteinase inhibitors of the four animal sera. A. contortrix laticinctus fraction 1 also had a high specific fibrinolytic ac tivity and no hemorrhagic activity. However, the fibrinolytic activity was neutralized by Didelphis virginiana (Virginia opossum) serum. (C) 1999 Else vier Science Inc. All rights reserved.