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The Siege of Charles-Towne was a naval blockade on the city of Charles-Towne, set up by the pirate Edward Thatch, to obtain medicines for Nassau. The blockade lasted for a week, in which there were no responses from the governor, Wyatt. This prompted Thatch's fellow pirate, the Assassin Edward Kenway, to infiltrate the city and steal medicines, ending the governor's life in the process.
Edward Thatch was approached by Benjamin Hornigold about the lack of medicines needed for the cure of diseases which plagued the Pirates' Republic. Not wanting to attack Royal Navy ships, Thatch and Kenway decided to recover medicines from the underwater shipwreck of San Ignacio, a ship of the ill-fated 1715 Spanish Treasure Fleet. However, the medicines recovered by Kenway were spoilt, which made attacking Royal Navy ships the only choice of obtaining medicines.
Subsequently, the Queen Anne's Revenge and the Benjamin attacked a British Man O' War, but the attack was unsuccessful, as the Benjamin suffered heavy damages and the Queen Anne's Revenge was forced to dock at Mariguana Island. Kenway then came to aid Thatch in his ship, the Jackdaw. Having rescued Thatch from the British Army, Kenway took the helm of the Queen Anne's Revenge and managed to board the Man O' War and steal medicines. Not having enough medicines, Thatch decided to obtain more from the source, Charles-Towne.
Thatch captured many residents of Charles-Towne and tied them on the Queen Anne's Revenge, along with the crew of the Man O' War which he attacked previously. After a week of the blockade, Kenway arrived and told Thatch to stop, or he would be wanted by the Royal Navy. Kenway decided to take matters into his own hands and sailed the Jackdaw to the marshes of Charles-Towne. He then tailed a gunboat of soldiers who were about to meet the governor; along the way, they were hailed by several guards, only to flee when one was snatched from the shore and killed by a crocodile. Kenway stealthily tailed them into Charles-Towne, and eavesdropped a conversation between the soldiers and Wyatt, the town's governor. However, the guards saw the Jackdaw and raised an alarm, revealing Kenway's presence. After spotting Kenway, Wyatt began to run towards his mansion, but was eventually chased down and killed by Kenway. Kenway stole the key and the pirates stole medicines and the ingredients to make more doses, then ending the blockade.
Despite the success, Thatch decided to take the King's pardon and settled in the pirate camp of Ocracoke in North Carolina. However, the success of the blockade made Alexander Spotswood order Robert Maynard to besiege Ocracoke. Thatch's ship was destroyed, and the infamous pirate tried to escape with Edward Kenway, but was killed while boarding a Man O' War.