63
Views
0
CrossRef citations to date
0
Altmetric
Research Article

Design, synthesis and biological evaluation of novel 3C-like protease inhibitors as lead compounds against SARS-CoV-2

, , , , , ORCID Icon, ORCID Icon & ORCID Icon show all
Pages 887-903 | Received 12 Jan 2024, Accepted 15 Mar 2024, Published online: 15 Apr 2024

References

  • Zhu N, Zhang D, Wang W et al. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med. 382(8), 727–733 (2020).
  • Yang X, Yu Y, Xu J et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir. Med. 8(5), 475–481 (2020).
  • Wu F, Zhao S, Yu B et al. A new coronavirus associated with human respiratory disease in China. Nature 579(7798), 265–269 (2020).
  • Hu B, Guo H, Zhou P, Shi Z-L. Characteristics of SARS-CoV-2 and COVID-19. Nat. Rev. Microbiol. 19(3), 141–154 (2020).
  • Zhou P, Yang X-L, Wang X-G et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579(7798), 270–273 (2020).
  • Hegyi A, Ziebuhr J. Conservation of substrate specificities among coronavirus main proteases. J. Gen. Virol. 83(3), 595–599 (2002).
  • Xiong M, Su H, Zhao W, Xie H, Shao Q, Xu Y. What coronavirus 3C-like protease tells us: from structure, substrate selectivity, to inhibitor design. Med. Res. Rev. 41(4), 1965–1998 (2021).
  • Jin Z, Du X, Xu Y et al. Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature 582(7811), 289–293 (2020).
  • Yang H, Yang M, Ding Y et al. The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor. Proc. Natl Acad. Sci. USA 100(23), 13190–13195 (2003).
  • Fan K, Ma L, Han X et al. The substrate specificity of SARS coronavirus 3C-like proteinase. Biochem. Biophys. Res. Commun. 329(3), 934–940 (2005).
  • Galasiti Kankanamalage AC, Kim Y, Damalanka VC et al. Structure-guided design of potent and permeable inhibitors of MERS coronavirus 3CL protease that utilize a piperidine moiety as a novel design element. Eur. J. Med. Chem. 150, 334–346 (2018).
  • Bjorkman P, Yang H, Xie W et al. Design of wide-spectrum inhibitors targeting coronavirus main proteases. PLOS Biol. 3(10) (2005).
  • Hattori S-I, Higashi-Kuwata N, Hayashi H et al. A small molecule compound with an indole moiety inhibits the main protease of SARS-CoV-2 and blocks virus replication. Nat. Commun. 12(1) (2021).
  • Zhang K, Wang T, Li M et al. Discovery of quinazolin-4-one-based non-covalent inhibitors targeting the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 Mpro). Eur. J. Med. Chem. 257, 115487 (2023).
  • Citarella A, Scala A, Piperno A, Micale N. SARS-CoV-2 Mpro: a potential target for peptidomimetics and small-molecule inhibitors. Biomolecules 11(4) (2021).
  • Drayman N, Demarco JK, Jones KA et al. Masitinib is a broad coronavirus 3CL inhibitor that blocks replication of SARS-CoV-2. Science 373(6557), 931–936 (2021).
  • Zumla A, Chan JFW, Azhar EI, Hui DSC, Yuen K-Y. Coronaviruses – drug discovery and therapeutic options. Nat. Rev. Drug Discov. 15(5), 327–347 (2016).
  • Pillaiyar T, Manickam M, Namasivayam V, Hayashi Y, Jung S-H. An overview of severe acute respiratory syndrome-coronavirus (SARS-CoV) 3CL protease inhibitors: peptidomimetics and small molecule chemotherapy. J. Med. Chem. 59(14), 6595–6628 (2016).
  • La Monica G, Bono A, Lauria A, Martorana A. Targeting SARS-CoV-2 main protease for treatment of COVID-19: covalent inhibitors structure–activity relationship insights and evolution perspectives. J. Med. Chem. 65(19), 12500–12534 (2022).
  • Owen DR, Allerton CMN, Anderson AS et al. An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19. Science 374(6575), 1586–1593 (2021).
  • Su H, Yao S, Zhao W et al. Identification of pyrogallol as a warhead in design of covalent inhibitors for the SARS-CoV-2 3CL protease. Nat. Commun. 12(1) (2021).
  • Dai W, Zhang B, Jiang X-M et al. Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science 368(6497), 1331–1335 (2020).
  • Qiao J, Li Y-S, Zeng R et al. SARS-CoV-2 Mpro inhibitors with antiviral activity in a transgenic mouse model. Science 371(6536), 1374–1378 (2021).
  • Sacco MD, Ma C, Lagarias P et al. Structure and inhibition of the SARS-CoV-2 main protease reveal strategy for developing dual inhibitors against Mpro and cathepsin L. Sci. Adv. 6(50), eabe0751 (2020).
  • Huang Q, Quan B, Chen Y et al. Discovery of alpha-ketoamide inhibitors of SARS-CoV-2 main protease derived from quaternized P1 groups. Bioorg. Chem. 143, 107001 (2024).
  • Zhang H, Zhou K, Peng F et al. Novel small-molecule inhibitors of SARS-CoV-2 main protease with nanomolar antiviral potency. J. Infect. 88(2), 211–214 (2024).
  • Unoh Y, Uehara S, Nakahara K et al. Discovery of S-217622, a noncovalent oral SARS-CoV-2 3CL protease inhibitor clinical candidate for treating COVID-19. J. Med. Chem. 65(9), 6499–6512 (2022).
  • Jiang Z, Feng B, Zhang Y et al. Discovery of novel non-peptidic and non-covalent small-molecule 3CLpro inhibitors as potential candidate for COVID-19 treatment. Signal Transduct. Target. Ther. 8(1) (2023).
  • Su H-X, Yao S, Zhao W-F et al. Anti-SARS-CoV-2 activities in vitro of Shuanghuanglian preparations and bioactive ingredients. Acta Pharmacol. Sin. 41(9), 1167–1177 (2020).
  • Kitamura N, Sacco MD, Ma C et al. Expedited approach toward the rational design of noncovalent SARS-CoV-2 main protease inhibitors. J. Med. Chem. 65(4), 2848–2865 (2021).
  • Lamb YN. Nirmatrelvir plus ritonavir: first approval. Drugs 82(5), 585–591 (2022).
  • Marzolini C, Kuritzkes DR, Marra F et al. Recommendations for the management of drug–drug interactions between the COVID-19 antiviral nirmatrelvir/ritonavir (Paxlovid) and comedications. Clin. Pharmacol. Ther. 112(6), 1191–1200 (2022).
  • Sindelar M, McCabe D, Carroll E. Tacrolimus drug–drug interaction with nirmatrelvir/ritonavir (Paxlovid™) managed with phenytoin. J. Med. Toxicol. 19(1), 45–48 (2022).
  • Yang H, You M, Shu X et al. Design, synthesis and biological evaluation of peptidomimetic benzothiazolyl ketones as 3CLpro inhibitors against SARS-CoV-2. Eur. J. Med. Chem. 257, 115512 (2023).
  • Mukae H, Yotsuyanagi H, Ohmagari N et al. A randomized phase 2/3 study of ensitrelvir, a novel oral SARS-CoV-2 3C-like protease inhibitor, in Japanese patients with mild-to-moderate COVID-19 or asymptomatic SARS-CoV-2 infection: results of the phase 2a part. Antimicrob. Agents Chemother. 66(10), e00697–00622 (2022).
  • Zhang C-H, Stone EA, Deshmukh M et al. Potent noncovalent inhibitors of the main protease of SARS-CoV-2 from molecular sculpting of the drug perampanel guided by free energy perturbation calculations. ACS Cent. Sci. 7(3), 467–475 (2021).
  • Kneller DW, Li H, Galanie S et al. Structural, electronic, and electrostatic determinants for inhibitor binding to subsites S1 and S2 in SARS-CoV-2 main protease. J. Med. Chem. 64(23), 17366–17383 (2021).
  • Han SH, Goins CM, Arya T et al. Structure-based optimization of ML300-derived, noncovalent inhibitors targeting the severe acute respiratory syndrome coronavirus 3CL protease (SARS-CoV-2 3CLpro). J. Med. Chem. 65(4), 2880–2904 (2021).
  • Ma C, Xia Z, Sacco MD et al. Discovery of di- and trihaloacetamides as covalent SARS-CoV-2 main protease inhibitors with high target specificity. J. Am. Chem. Soc. 143(49), 20697–20709 (2021).
  • Huang Z, Yu X, Huang X. α-Hypervalent iodine functionalized phosphonium and arsonium ylides and their tandem reaction as umpolung reagents. J. Org. Chem. 67(23), 8261–8264 (2002).
  • Ma L, Pei H, Lei L et al. Structural exploration, synthesis and pharmacological evaluation of novel 5-benzylidenethiazolidine-2,4-dione derivatives as iNOS inhibitors against inflammatory diseases. Eur. J. Med. Chem. 92, 178–190 (2015).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.