Naja nigricollis phospholipase A2 enzymes (PLA2)

Naja nigricollis phospholipase A2 (PLA2) enzymes are a group of potent toxins found in the venom of the black-necked spitting cobra, a medically significant elapid snake native to sub-Saharan Africa. These enzymes, which include several isoforms such as CM-I, CM-II, CM-III, and the highly potent CM-IV, are responsible for a variety of toxic effects including anticoagulation, cardiotoxicity, and local tissue necrosis. The basic isoform CM-IV is particularly notable for its ability to inhibit blood coagulation by binding directly to Factor Xa and blocking the formation of the prothrombinase complex, a process that occurs independently of its enzymatic activity. In addition to systemic coagulopathy, these enzymes cause significant local inflammation and cell death at the site of the bite, contributing to the severe morbidity associated with spitting cobra envenomation. As key drivers of venom pathology, Naja nigricollis PLA2s are primary therapeutic targets for both traditional antivenoms and emerging small-molecule inhibitors like varespladib, which aim to neutralize their toxic actions and improve patient survival.

Other names

CM-ICM-IICM-IIICM-IVBasic phospholipase A2Acidic phospholipase A2Phosphatidylcholine 2-acylhydrolase

Varespladib and its derivatives act as competitive inhibitors that bind to the active site of phospholipase A2 enzymes, preventing the hydrolysis of phospholipids and neutralizing non-enzymatic interactions with blood coagulation factors such as Factor Xa.