Rupintrivir is a potent, irreversible inhibitor of human rhinovirus (HRV) 3C protease with a mean EC50 value of 0.023μM for inhibiting the replication of all HRV serotypes [1]. Rupintrivir binds in a unique conformation to the active site of SARS-CoV-2 Mpro, splitting the catalytic cysteine and histidine residues and inhibiting the activity of SARS-CoV-2 [2]. Rupintrivir has been widely used to inhibit the replication of enterovirus 71 (EV 71), and is combined with IFN-α to develop combination therapies that efficiently eliminate the virus [3].
In vitro, Rupintrivir treatment for 72 hours significantly reduced the levels of Norovirus RNA in HG23 cells, with an EC50 value of 0.3µM[4]. Treatment with 100nM Rupintrivir for 48 hours suppressed the HRV-induced hypersecretion of cytokines IL-6 and IL-4 in precision-cut lung slices (PCLS) from house dust mite (HDM)-sensitized mice [5].
In vivo, Rupintrivir treatment via daily intraperitoneal injection at a dose of 0.1mg/kg for 10 days can alleviate EV 71 virus-induced necrotizing myositis in suckling mice and increase the survival rate[6].
References:
[1] Patick A K, Binford S L, Brothers M A, et al. In vitro antiviral activity of AG7088, a potent inhibitor of human rhinovirus 3C protease[J]. Antimicrobial agents and chemotherapy, 1999, 43(10): 2444-2450.
[2] Lockbaum G J, Henes M, Lee J M, et al. Pan-3C protease inhibitor rupintrivir binds SARS-CoV-2 main protease in a unique binding mode[J]. Biochemistry, 2021, 60(39): 2925-2931.
[3] Hung H C, Wang H C, Shih S R, et al. Synergistic inhibition of enterovirus 71 replication by interferon and rupintrivir[J]. Journal of Infectious Diseases, 2011, 203(12): 1784-1790.
[4] Rocha-Pereira J, Nascimento M S J, Ma Q, et al. The enterovirus protease inhibitor rupintrivir exerts cross-genotypic anti-norovirus activity and clears cells from the norovirus replicon[J]. Antimicrobial agents and chemotherapy, 2014, 58(8): 4675-4681.
[5] Danov O, Lasswitz L, Obernolte H, et al. Rupintrivir reduces RV-induced TH-2 cytokine IL-4 in precision-cut lung slices (PCLS) of HDM-sensitized mice ex vivo[J]. Respiratory research, 2019, 20(1): 228.
[6] Zhang X, Song Z, Qin B, et al. Rupintrivir is a promising candidate for treating severe cases of enterovirus-71 infection: evaluation of antiviral efficacy in a murine infection model[J]. Antiviral research, 2013, 97(3): 264-269.
Rupintrivir是一种强效、不可逆的human rhinovirus (HRV) 3C protease抑制剂，抑制所有HRV血清型复制的平均EC50值为0.023μM[1]。Rupintrivir以独特的构象结合到SARS-CoV-2 Mpro的活性位点，将催化半胱氨酸和组氨酸残基分开，从而抑制SARS-CoV-2的活性[2]。Rupintrivir已被广泛用于抑制肠道病毒 71型(EV 71)的复制，并与IFN-α联合开发可有效清除病毒的联合疗法[3]。
在体外，Rupintrivir处理HG23细胞72小时，显著降低了诺如病毒(Norovirus)RNA的水平，EC50值为0.3μM[5]。100nM的Rupintrivir处理48小时，抑制了屋尘螨(HDM)致敏小鼠的精确切割肺切片(PCLS)中HRV诱导的细胞因子IL-6和IL-4的过度分泌[5]。
在体内，每日腹腔注射0.1mg/kg剂量的Rupintrivir，连续10天，可减轻EV 71病毒诱导的乳鼠坏死性肌炎，并提高存活率[6]。