“…The inhibitors against serine protease of HIV, together with reverse transcriptase inhibitors, have constituted the regime of highly active antiretroviral therapy (HAART) to achieve HIV virological suppression. Beside non-competitive or non-covalent inhibitors ( Ratia et al., 2008 ; Xu et al., 2021 ; Liang et al., 2022 ), small molecule compounds covalently linked to thiol group have also been discovered because of the high nucleophilicity of thiol group on cysteine residue located in the catalytically active site of cysteine protease ( Dai et al., 2020 ; Liu et al., 2021 ). Paxlovid, a drug under investigation which consists of covalent coronavirus cysteine protease inhibitor (nirmatrelvir) and an enhancer (ritonavir) has been authorized for the emergency use to treat mild-to-moderate COVID-19.…”