Quinazolinone-based subchemotypes for targeting HIV-1 capsid protein: design and synthesis

Campbell EM, Hope TJ. HIV-1 capsid: the multifaceted key player in HIV-1 infection. Nat Rev Microbiol. 2015;13:471–83.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rebensburg SV, Wei GC, Larue RC, Lindenberger J, Francis AC, Annamalai AS, et al. Sec24C is an HIV-1 host dependency factor crucial for virus replication. Nat Microbiol. 2021;6:435–44.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Matreyek KA, Yucel SS, Li X, Engelman A. Nucleoporin NUP153 phenylalanine-glycine motifs engage a common binding pocket within the HIV-1 capsid protein to mediate lentiviral infectivity. PLoS Pathog. 2013;9:e1003693.

Article  PubMed  PubMed Central  Google Scholar 

Price AJ, Fletcher AJ, Schaller T, Elliott T, Lee K, KewalRamani VN, et al. CPSF6 defines a conserved capsid interface that modulates HIV-1 replication. Plos Pathogens. 2012;8. https://doi.org/10.1371/journal.ppat.1002896

Price AJ, Jacques DA, McEwan WA, Fletcher AJ, Essig S, Chin JW, et al. Host cofactors and pharmacologic ligands share an essential interface in HIV-1 capsid that is lost upon disassembly. PLoS Pathog. 2014;10:e1004459.

Article  PubMed  PubMed Central  Google Scholar 

Bhattacharya A, Alam SL, Fricke T, Zadrozny K, Sedzicki J, Taylor AB, et al. Structural basis of HIV-1 capsid recognition by PF74 and CPSF6. Proc Natl Acad Sci USA. 2014;111:18625–30.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gres AT, Kirby KA, KewalRamani VN, Tanner JJ, Pornillos O, Sarafianos SG. X-ray crystal structures of native HIV-1 capsid protein reveal conformational variability. Science. 2015;349:99–103.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bester SM, Wei GC, Zhao HY, Adu-Ampratwum D, Iqbal N, Courouble VV, et al. Structural and mechanistic bases for a potent HIV-1 capsid inhibitor. Science. 2020;370:360–4.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Link JO, Rhee MS, Tse WC, Zheng J, Somoza JR, Rowe W, et al. Clinical targeting of HIV capsid protein with a long-acting small molecule. Nature. 2020;584:614–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gillis EP, Parcella K, Bowsher M, Cook JH, Iwuagwu C, Naidu BN, et al. Potent long-acting inhibitors targeting the HIV-1 capsid based on a versatile quinazolin-4-one scaffold. J Med Chem. 2023;66:1941–54.

Article  CAS  PubMed  Google Scholar 

Wang C, Huang H, Mallon K, Valera L, Parcella K, Cockett MI, et al. Antiviral properties of HIV-1 capsid inhibitor GSK878. Antimicrob Agents Chemother. 2023;67:e0169422.

Article  PubMed  Google Scholar 

Rankovic S, Ramalho R, Aiken C, Rousso I. PF74 reinforces the HIV-1 capsid to impair reverse transcription-induced uncoating. J Virol. 2018;92:e00845-18.

Article  PubMed  PubMed Central  Google Scholar 

Paik J. Lenacapavir: first approval. Drugs. 2022;82:1499–504.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Margot N, Vanderveen L, Naik V, Ram R, Parvangada P, Martin R, et al. Phenotypic resistance to lenacapavir and monotherapy efficacy in a proof-of-concept clinical study. J Antimicrob Chemother. 2022;77:989–95.

Article  CAS  PubMed  Google Scholar 

Margot NA, Naik V, VanderVeen L, Anoshchenko O, Singh R, Dvory-Sobol H, et al. Resistance analyses in highly treatment-experienced people with human immunodeficiency virus (HIV) treated with the novel capsid HIV inhibitor lenacapavir. J Infect Dis. 2022;226:1985–91.

Article  CAS  PubMed  Google Scholar 

Wirden M, Pouderoux C, Peytavin G, Abdi B, Fayçal A, Palich R, et al. Ultra-rapid selection of the N74D capsid inhibitor resistance mutation after 3 weeks on lenacapavir. J Antimicrob Chemother. 2024. https://doi.org/10.1093/jac/dkae115.

Akther T, McFadden WM, Zhang H, Kirby KA, Sarafianos SG, Wang Z. Design and synthesis of new GS-6207 subtypes for targeting HIV-1 capsid protein. Int J Mol Sci. 2024;25. https://doi.org/10.3390/ijms25073734.

Wang L, Casey MC, Vernekar SKV, Sahani RL, Kankanala J, Kirby KA, et al. Novel HIV-1 capsid-targeting small molecules of the PF74 binding site. Eur J Med Chem. 2020;204:112626.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang B, Zhu C, Chan ASC, Lu G. Discovery of a first-in-class Aurora A covalent inhibitor for the treatment of triple negative breast cancer. Eur J Med Chem. 2023;256:115457.

Article  CAS  PubMed  Google Scholar 

Fan J, Dai Y, Shao J, Peng X, Wang C, Cao S, et al. Design, synthesis and biological evaluation of pyrazolylaminoquinazoline derivatives as highly potent pan-fibroblast growth factor receptor inhibitors. Bioorg Med Chem Lett. 2016;26:2594–9.

Article  CAS  PubMed  Google Scholar 

Carpino LA. 1-Hydroxy-7-azabenzotriazole. An efficient peptide coupling additive. J Am Chem Soc. 1993;115:4397–8.

Article  CAS  Google Scholar 

Vernekar SKV, Sahani RL, Casey MC, Kankanala J, Wang L, Kirby KA, et al. Toward structurally novel and metabolically stable HIV-1 capsid-targeting small molecules. Viruses. 2020;12. https://doi.org/10.3390/v12040452.

Schrödinger Inc. Schrödinger Small-Molecule Drug Discovery Suite 2021-3, Schrödinger. New York, NY: LLC; 2021.

Google Scholar 

Jorgensen WL, Maxwell DS, TiradoRives J. Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J Am Chem Soc. 1996;118:11225–36.

Article  CAS  Google Scholar 

LigPrep SR. Schrödinger. New York, NY: LLC; 2021.

Friesner RAB, J L, Murphy RB, Halgren TA, Klicic JJ, Mainz DT, et al. Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem. 2004;47:1739–49.

Article  CAS  PubMed  Google Scholar 

Schrödinger. The PyMOL Molecular Graphics System V. NewYork, NY, USA: Schrödinger, LLC; 2021.

Google Scholar 

Pornillos O, Ganser-Pornillos BK, Kelly BN, Hua Y, Whitby FG, Stout CD, et al. X-ray structures of the hexameric building block of the HIV capsid. Cell. 2009;137:1282–92.

Article  PubMed  PubMed Central  Google Scholar 

Lo MC, Aulabaugh A, Jin G, Cowling R, Bard J, Malamas M, et al. Evaluation of fluorescence-based thermal shift assays for hit identification in drug discovery. Anal Biochem. 2004;332:153–9.

Article  CAS  PubMed  Google Scholar 

Miyazaki Y, Doi N, Koma T, Adachi A, Nomaguchi M. Novel in vitro screening system based on differential scanning fluorimetry to search for small molecules against the disassembly or assembly of HIV-1 capsid protein. Front Microbiol. 2017;8:1413.

Article  PubMed  PubMed Central  Google Scholar 

Pantoliano MW, Petrella EC, Kwasnoski JD, Lobanov VS, Myslik J, Graf E, et al. High-density miniaturized thermal shift assays as a general strategy for drug discovery. J Biomol Screen. 2001;6:429–40.

Article  CAS  PubMed  Google Scholar 

Adachi A, Gendelman HE, Koenig S, Folks T, Willey R, Rabson A, et al. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J Virol. 1986;59:284–91.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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