nsP2 Protease-IN-1 is a potent irreversible covalent inhibitor of Chikungunya (CHIKV) nsP2 cysteine protease with an IC 50 value of 60 nM. nsP2 Protease-IN-1 demonstrates potent antialphavirus activity, inhibiting CHIKV and VEEV replication with EC 50 = 0.01 and 0.3 µM, respectively.