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The Ndesu is fought as a boss at the end of Chapter 2-3 while still using the gatling guns in the Gambit but while stationary. The player must inflict so much damage to the Ndesu until it flinches and its plagas emerge from its body, then the player must shoot and destroy them.
The Ndesu will not be fighting Chris and Sheva alone. It will have back-up from some of the Town Majini. On the right side of the screen, there will be two armed with fire crossbows, and on the left side will be on Majini armed with a Molotov Cocktail, which all can do minor damage in comparison to the Ndesu's attacks.
When taking too many hits from the turrets, it becomes stunned. Its attacks includes:
Stomping: While close to Chris and Sheva, Ndesu will stomp on the Gambit which causes heavy damage.
Punch: Ndesu will try to inflict more heavy damage by swinging at the player. The player will be prompted to press the proper control buttons to successfully dodge this attack. This can also give the player somewhat of an advantage to allow the gun turrets to cool off if it is in danger of overheating.
Pound: A trademark attack by the Ndesu. With his hands clutched together, he will perform a double axe handle attack on the Gambit. He attempted this same attack on Chris, who barely dodged this during the cutscene.
Boulder: Ndesu displays tremendous strength by instantly digging out a boulder and throwing it at Chris and Sheva. The boulder can be destroyed by Chris and Sheva using their gun turrets.
Pole attack: Ndesu will take a large telephone pole and attack in the same manner as with his punch, by swinging it at the player. However, Ndesu will try to slam this object on the Gambit, causing more heavy damage, so once again, the gun turrets are necessary to stun him before he can successfully execute this attack.
Ground Pound: This attack is executed in the same manner as the pound attack, only that while distant from Chris and Sheva, Ndesu will pound the ground, causing a powerful earthquake-like impact that causes a lot of damage. The player will be quickly prompted to press the correct buttons to easily brace themselves for this attack.
Charge: This is perhaps Ndesu's most dangerous attack as it will use its body to tackle the Gambit, which can cause the player to lose over 50% of health. This attack is hinted when Sheva says: "Something's wrong with him! Watch out!" or with Chris: "I don't like the looks of this! Keep firing!".
As mentioned before the gun turrets from both Chris and Sheva will be the key to defeating Ndesu. Once the player has inflicted enough damage in the beginning of the fight, two small plaga parasite will emerge from its body. The player must destroy them both before it's main weak point is exposed: a massive plaga parasite that will burst from Ndesu's spine. The player must inflict as much damage to this main weak spot as possible, before the parasite regresses back into Ndesu's body. This will not kill Ndesu in the first round, however, repeating this sequence once or twice, only there will be more of the small plaga parasites (four total) that must be destroyed before the main plaga is exposed again. As for the attacking Majini, it is recommended that they are destroyed while Ndesu is stunned from the gun turrets. Unfortunately, after the Majinis are killed, more will appear in their place (this is indicated by their sinister laugh or battle cry).
There will be oil canisters the player can shoot, causing an explosion to further stun and inflict heavy damage to Ndesu. This is recommended if Ndesu has four of the plaga parasites exposed and if he attacks with a boulder or pole (Ndesu will of course have to be close to the canisters for this to be effective). There will be only one canister in particular that will only be used for the Majini attacking with the crossbow.
For Ndesu's attacks there is a simple counter: Whatever he tries, keep shooting his head, and you will interrupt the attack. Be careful when he raises his arms and attempts to attack you or when he tries to tackle the Gambit as his head will shift from its initial position. The only attacks that you cannot counter by shooting his head is when he grabs a boulder or a telephone line and when you are prompted to dodge or hang on the Gambit.