HIV-1 capsid inhibitors: a sword to destroy the virus

Future Medicinal ChemistryVol. 14, No. 9 EditorialHIV-1 capsid inhibitors: a sword to destroy the virusXujie Zhang, Shujing Xu, Lin Sun, Dang Ding, Yucen Tao, Dongwei Kang, Xinyong Liu & Peng ZhanXujie Zhang https://orcid.org/0000-0003-1393-4665Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012, Jinan, Shandong, PR China, Shujing Xu https://orcid.org/0000-0002-7168-613XDepartment of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012, Jinan, Shandong, PR China, Lin SunDepartment of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012, Jinan, Shandong, PR China, Dang DingDepartment of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012, Jinan, Shandong, PR China, Yucen TaoDepartment of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012, Jinan, Shandong, PR China, Dongwei KangDepartment of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012, Jinan, Shandong, PR China, Xinyong Liu*Author for correspondence: E-mail Address: xinyongl@sdu.edu.cnDepartment of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012, Jinan, Shandong, PR China & Peng Zhan**Author for correspondence: E-mail Address: zhanpeng1982@sdu.edu.cnDepartment of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012, Jinan, Shandong, PR ChinaPublished Online:17 Mar 2022https://doi.org/10.4155/fmc-2022-0008AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit View articleAbstractKeywords: capsid inhibitorHIV-1lenacapavirphenylalanine derivativesprotein–protein interactionReferences1. Zhang X, Sun L, Meuser ME et al. Design, synthesis, and mechanism study of dimerized phenylalanine derivatives as novel HIV-1 capsid inhibitors. Eur. J. Med. Chem. 226, 113848 (2021).Crossref, Medline, CAS, Google Scholar2. Zila V, Müller TG, Müller B, Kräusslich HG. HIV-1 capsid is the key orchestrator of early viral replication. PLoS Pathog. 17(12), e1010109 (2021).Crossref, Medline, CAS, Google Scholar3. Le Sage V, Mouland AJ, Valiente-Echeverría F. Roles of HIV-1 capsid in viral replication and immune evasion. Virus Res. 193, 116–129 (2014).Crossref, Medline, Google Scholar4. Campbell EM, Hope TJ. HIV-1 capsid: the multifaceted key player in HIV-1 infection. Nat. Rev. Microbiol. 13(8), 471–483 (2015).Crossref, Medline, CAS, Google Scholar5. Sun L, Zhang X, Xu S et al. An insight on medicinal aspects of novel HIV-1 capsid protein inhibitors. Eur. J. Med. Chem. 217, 113380 (2021).Crossref, Medline, CAS, Google Scholar6. Blair WS, Pickford C, Irving SL et al. HIV capsid is a tractable target for small molecule therapeutic intervention. PLoS Pathog. 6(12), e1001220 (2010).Crossref, Medline, Google Scholar7. Saito A, Ferhadian D, Sowd GA et al. Roles of capsid-interacting host factors in multimodal inhibition of HIV-1 by PF74. J. Virol. 90(12), 5808–5823 (2016).Crossref, Medline, CAS, Google Scholar8. Yant SR, Mulato A, Hansen D et al. A highly potent long-acting small-molecule HIV-1 capsid inhibitor with efficacy in a humanized mouse model. Nat. Med. 25(9), 1377–1384 (2019).Crossref, Medline, CAS, Google Scholar9. Vidal SJ, Bekerman E, Hansen D et al. Long acting capsid inhibitor protects macaques from repeat SHIV challenges. Nature (2021).Google Scholar10. Link JO, Rhee MS, Tse WC et al. Clinical targeting of HIV capsid protein with a long-acting small molecule. Nature 584(7822), 614–618 (2020).Crossref, Medline, CAS, Google Scholar11. Bester SM, Wei G, Zhao H et al. Structural and mechanistic bases for a potent HIV-1 capsid inhibitor. Science 370(6514), 360–364 (2020).Crossref, Medline, CAS, Google Scholar12. Christensen DE, Ganser-Pornillos BK, Johnson JS et al. Reconstitution and visualization of HIV-1 capsid-dependent replication and integration in vitro. Science 370(6513), eabc8420 (2020).Crossref, Medline, CAS, Google Scholar13. Singh K, Gallazzi F, Hill KJ et al. GS-CA compounds: first-in-class HIV-1 capsid inhibitors covering multiple grounds. Front. Microbiol. 10, 1227 (2019).Crossref, Medline, Google Scholar14. Margot N, Ram R, Rhee M, Callebaut C. Absence of lenacapavir (GS-6207) phenotypic resistance in HIV gag cleavage site mutants and in isolates with resistance to existing drug classes. Antimicrob. Agents Chemother. 65(3), (2021).Crossref, Medline, Google Scholar15. Sun L, Dick A, Meuser ME et al. Design, synthesis, and mechanism study of benzenesulfonamide-containing phenylalanine derivatives as novel HIV-1 capsid inhibitors with improved antiviral activities. J. Med. Chem. 63(9), 4790–4810 (2020).Crossref, Medline, CAS, Google Scholar16. Meuser ME, Reddy PaN, Dick A et al. Rapid optimization of the metabolic stability of a human immunodeficiency virus type-1 capsid inhibitor using a multistep computational workflow. J. Med. Chem. 64(7), 3747–3766 (2021).Crossref, Medline, CAS, Google Scholar17. Sahani RL, Diana-Rivero R, Vernekar SKV et al. Design, synthesis and characterization of HIV-1 CA-targeting small molecules: conformational restriction of PF74. Viruses 13(3), 479 (2021).Crossref, Medline, CAS, Google Scholar18. Chia T, Nakamura T, Amano M et al. A small molecule, ACAi-028, with anti-HIV-1 activity targets a novel hydrophobic pocket on HIV-1 capsid. Antimicrob. Agents Chemother. 65(10), e0103921 (2021).Crossref, Medline, Google Scholar19. Xu S, Sun L, Huang B, Liu X, Zhan P. Medicinal chemistry strategies of targeting HIV-1 capsid protein for antiviral treatment. Future Med. Chem. 12(14), 1281–1284 (2020).Link, CAS, Google Scholar20. Ma Y, Frutos-Beltrán E, Kang D et al. Medicinal chemistry strategies for discovering antivirals effective against drug-resistant viruses. Chem. Soc. Rev. 50(7), 4514–4540 (2021).Crossref, Medline, CAS, Google ScholarFiguresReferencesRelatedDetailsCited ByThe discovery and design of novel HIV-1 capsid modulators and future perspectives15 December 2022 | Expert Opinion on Drug Discovery, Vol. 18, No. 1Design, Synthesis, and Mechanistic Study of 2-Pyridone-Bearing Phenylalanine Derivatives as Novel HIV Capsid Modulators7 November 2022 | Molecules, Vol. 27, No. 21Metabolite Identification of HIV-1 Capsid Modulators PF74 and 11L in Human Liver Microsomes16 August 2022 | Metabolites, Vol. 12, No. 8 Vol. 14, No. 9 Follow us on social media for the latest updates Metrics Downloaded 101 times History Received 13 January 2022 Accepted 24 February 2022 Published online 17 March 2022 Published in print May 2022 Information© 2022 Newlands PressKeywordscapsid inhibitorHIV-1lenacapavirphenylalanine derivativesprotein–protein interactionFinancial & competing interests disclosureThe authors gratefully acknowledge financial support from National Natural Science Foundation of China (NSFC nos. 82173677, 81773574), Science Foundation for Outstanding Young Scholars of Shandong Province (no. ZR2020JQ31), the Foreign cultural and educational experts Project (no. GXL20200015001), the Shandong Provincial Key research and development project (no. 2019JZZY021011), Chang Jiang Scholars Program of Ministry of Education, People's Republic of China (no. 2021108), Taishan Scholar Program at Shandong Province, Qilu Young Scholars Program of Shandong University. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.No writing assistance was utilized in the production of this manuscript.PDF download