Mortality due to
snakebite is a serious public health problem, and available
therapeutics are known to induce debilitating side effects.
Traditional medicine suggests that seeds of Mucuna pruriens can provide protection against the effects of
snakebite. Our aim is to identify the
protein(s) that may be important for
snake venom neutralization and elucidate its mechanism of action. To this end, we have identified and purified a
protein from M. pruriens, which we have named MP-4. The full-length
polypeptide sequence of MP-4 was obtained through N-terminal sequencing of
peptide fragments. Sequence analysis suggested that the
protein may belong to the Kunitz-type
protease inhibitor family and therefore may potentially neutralize the
proteases present in
snake venom. Using various structural and biochemical tools coupled with in vivo assays, we are able to show that MP-4 does not afford direct protection against
snake venom because it is actually a poor inhibitor of
serine proteases. Further experiments showed that
antibodies generated against MP-4 cross-react with the whole
venom and provide protection to mice against Echis carinatus
snake venom. This study shows that the MP-4 contributes significantly to the
snake venom neutralization activity of M. pruriens seeds through an indirect antibody-mediated mechanism.