Dr. Curt Connors has been turned into Lizard again. This time, he has a bite that turns anyone who is bitten into Lizards. The Triskelion goes under lockdown when Spider-Man's team and the S.H.I.E.L.D. Academy personnel get infected and attack Spider-Man. With help from an item in Nick Fury's office and with the help of Iron Spider, Leo Fitz, and Jemma Simmons, Spider-Man must work on an antidote in order to restore everyone to normal. Meanwhile, Agent Venom and Rhino guard Doctor Octopus' cell during the outbreak just in case he plans any escapes from his cell. Once everyone is cured, Spider-Man witnesses Doctor Octopus and Rhino making off with Agent Venom.
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