Protease binds protease inhibitors

Stable Identifier
Reaction [binding]
Homo sapiens
Related Species
Human immunodeficiency virus 1
gag-pol(489-587) binds protease inhibitors
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Antiretroviral (ARV) therapy, comprising a backbone of two nucleos(t)ide reverse transcriptase inhibitors (NRTIs) plus another ARV, has helped extend life expectancy in people living with HIV (Orkin et al. 2018).

Lopinavir is an antiretroviral protease inhibitor used in combination with other antiretrovirals in the treatment of HIV-1 infection. Like many other protease inhibitors, lopinavir is a peptidomimetic molecule; it contains a hydroxyethylene scaffold that mimics the peptide linkage typically targeted by the HIV-1 protease enzyme but which itself cannot be cleaved, thus preventing the acivity of the HIV-1 protease (Reddy et al. 2007). Another HIV protease inhibitor, darunavir, prevents HIV replication through binding to the enzyme, stopping the dimerization and the catalytic activity of HIV-1 protease (De Meyer et al. 2005). In particular, it inhibits the cleavage of HIV encoded Gag-Pol proteins in cells that have been infected with the virus, halting the formation of mature virus particles, which spread the infection (Davis et al. 2012).

Lopinavir in combination with other drugs is currently being investigated for patients with COVID-19 (many clinical trials, example registration nos. ChiCTR2000029603, ChiCTR2000029539, NCT04255017, NCT04261270) (Harrison 2020, Cao et al. 2020, Deng et al. 2020, Martinez 2020).
Literature References
PubMed ID Title Journal Year
32152082 Compounds with therapeutic potential against novel respiratory 2019 coronavirus

Martinez, MA

Antimicrob. Agents Chemother. 2020
15917527 TMC114, a novel human immunodeficiency virus type 1 protease inhibitor active against protease inhibitor-resistant viruses, including a broad range of clinical isolates

Tahri, A, De Meyer, S, de B├ęthune, MP, Pauwels, R, Jochmans, D, Surleraux, D, Azijn, H, Wigerinck, P

Antimicrob. Agents Chemother. 2005
22508308 Activity of human immunodeficiency virus type 1 protease inhibitors against the initial autocleavage in Gag-Pol polyprotein processing

Naiman, NE, Davidoff, KS, Soule, EE, Daniels, SI, Davis, DA, Yarchoan, R

Antimicrob. Agents Chemother. 2012
32205870 Coronavirus puts drug repurposing on the fast track

Harrison, C

Nat. Biotechnol. 2020
32171872 Arbidol combined with LPV/r versus LPV/r alone against Corona Virus Disease 2019: A retrospective cohort study

Zhang, H, Liu, X, Li, C, Li, X, Deng, L, Hong, Z, Xia, J, Zeng, Q

J. Infect. 2020
32187464 A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19

Liu, Y, Luo, S, Wang, S, Huang, H, Cao, B, Yuan, Y, Tu, S, Li, C, Zhan, H, Fan, G, Xia, J, Qu, Z, Hu, X, Gu, X, Dong, C, Dong, X, Lu, S, Hayden, FG, Song, B, Zhang, D, Xiang, J, Zhou, F, Xu, J, Qiu, F, Liu, Z, Li, K, Yu, T, Wu, J, Wei, Y, Huang, C, Wang, Y, Jia, C, Li, X, Liu, X, Zhou, X, Zou, J, Wei, M, Zhang, Y, Ge, Q, He, J, Chen, N, Guo, L, Bai, T, Gong, F, Chen, H, Pan, L, Jaki, T, Cai, Y, Wu, X, Xie, X, Horby, PW, Wang, J, Wen, D, Cheng, F, Li, H, Wang, J, Ruan, S, Peng, L, Ruan, L, Zhang, L, Shang, L, Liu, W, Wang, K, Li, H, Wang, C

N. Engl. J. Med. 2020
17696512 Design and synthesis of HIV-1 protease inhibitors incorporating oxazolidinones as P2/P2' ligands in pseudosymmetric dipeptide isosteres

Cao, H, Rana, TM, Nalam, MN, Reddy, GS, Ali, A, Anjum, SG, Schiffer, CA, Nathans, RS

J. Med. Chem. 2007
Name Identifier Synonyms
Human immunodeficiency virus infectious disease DOID:526 HIV infection
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