The crystal structure of chikungunya (CHIKV) virus capsid protease domain has been determined at 2.2 Å. Structure reveals a chymotrypsin-like protease fold with a conserved hydrophobic pocket in CHIKV capsid protein (CP) for interaction with the cytoplasmic tail of E2 (cdE2) similar to the capsid protein of other alphaviruses. Molecular contacts between CP-cdE2 were determined by fitting structures of CHIKV CP and cdE2 into the cryo-EM map of Venezuelan equine encephalitis virus (VEEV). Binding of (S)-(+)-Mandelic acid (MDA) and Ethyl 3-aminobenzoate (EAB) to the hydrophobic pocket of CP was evaluated by molecular docking. Surface plasmon resonance (SPR) and fluorescence spectroscopy experiments confirmed MDA and EAB binding to the CP. The binding constants (K_D) obtained from SPR for MDA and EAB were 1.2 × 10⁻³ M and 0.2 × 10⁻⁹ M, respectively. This study adds to the understanding of chikungunya virus structural proteins and may serve as the basis for antiviral development against chikungunya disease.

基孔肯雅（CHIKV）病毒衣壳蛋白酶结构域的晶体结构已确定为2.2。结构揭示了胰凝乳蛋白酶样蛋白酶折叠，在CHIKV衣壳蛋白（CP）中具有保守的疏水口袋，与其他α病毒的衣壳蛋白相似，可与E2的胞质尾部（cdE2）相互作用。CP-cdE2之间的分子接触是通过将CHIKV CP和cdE2的结构拟合到委内瑞拉马脑炎病毒（VEEV）的冷冻EM图中来确定的。通过分子对接评价（S）-（+）-扁桃酸（MDA）和3-氨基苯甲酸乙酯（EAB）与CP的疏水口袋的结合。表面等离子体共振（SPR）和荧光光谱实验证实了MDA和EAB与CP的结合。结合常数（K _D从SPR获得的MDA和EAB值分别为1.2×10 ^-3 M和0.2×10 ^-9M。这项研究增加了对基孔肯雅病毒结构蛋白的了解，并可以作为抗基孔肯雅病抗病毒药物开发的基础。