Peptide-Based Inhibitors for SARS-CoV-2 and SARS-CoV

Overview

Journal Adv Ther (Weinh)

Date 2021 Sep 13

PMID 34514085

Citations 8

Authors

Disha Panchal

Jeena Kataria

Kamiya Patel

Kaytlyn Crowe

Varun Pai

Abdul-Rahman Azizogli

Neil Kadian

Sreya Sanyal

Abhishek Roy

Joseph Dodd-O

Amanda M Acevedo-Jake

Vivek A Kumar

Affiliations

Soon will be listed here.

Abstract

The COVID-19 (coronavirus disease) global pandemic, caused by the spread of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus, currently has limited treatment options which include vaccines, anti-virals, and repurposed therapeutics. With their high specificity, tunability, and biocompatibility, small molecules like peptides are positioned to act as key players in combating SARS-CoV-2, and can be readily modified to match viral mutation rate. A recent expansion of the understanding of the viral structure and entry mechanisms has led to the proliferation of therapeutic viral entry inhibitors. In this comprehensive review, inhibitors of SARS and SARS-CoV-2 are investigated and discussed based on therapeutic design, inhibitory mechanistic approaches, and common targets. Peptide therapeutics are highlighted, which have demonstrated in vitro or in vivo efficacy, discuss advantages of peptide therapeutics, and common strategies in identifying targets for viral inhibition.

Citing Articles

Peptide-Based Inhibitors of Protein-Protein Interactions (PPIs): A Case Study on the Interaction Between SARS-CoV-2 Spike Protein and Human Angiotensin-Converting Enzyme 2 (hACE2).

Rakhmetullina A, Zielenkiewicz P, Odolczyk N Biomedicines. 2024; 12(10).

PMID: 39457672 PMC: 11504900. DOI: 10.3390/biomedicines12102361.

Study of Potential Blocking Peptides Targeting the SARS-CoV-2 RBD/hACE2 Interaction.

Villada-Troncoso S, Arevalo-Romero J, Hernandez Rivera V, Pedraza-Escalona M, Perez-Tapia S, Espejo-Mojica A Pharmaceuticals (Basel). 2024; 17(9).

PMID: 39338402 PMC: 11435355. DOI: 10.3390/ph17091240.

Antiviral Protein-Protein Interaction Inhibitors.

Markovic V, Szczepanska A, Berlicki L J Med Chem. 2024; 67(5):3205-3231.

PMID: 38394369 PMC: 10945500. DOI: 10.1021/acs.jmedchem.3c01543.

Antiviral fibrils of self-assembled peptides with tunable compositions.

Dodd-O J, Roy A, Siddiqui Z, Jafari R, Coppola F, Ramasamy S Nat Commun. 2024; 15(1):1142.

PMID: 38326301 PMC: 10850501. DOI: 10.1038/s41467-024-45193-3.

Evaluation of Potential Peptide-Based Inhibitors against SARS-CoV-2 and Variants of Concern.

Boshah H, Samkari F, Valle-Perez A, Alsawaf S, Aldoukhi A, Bilalis P Biomed Res Int. 2023; 2023:3892370.

PMID: 37869628 PMC: 10589072. DOI: 10.1155/2023/3892370.

References

Lee S, Meyler P, Mozel M, Tauh T, Merchant R . Asymptomatic carriage and transmission of SARS-CoV-2: What do we know?. Can J Anaesth. 2020; 67(10):1424-1430. PMC: 7266417. DOI: 10.1007/s12630-020-01729-x. View

Han Y, Gao Z, Chen L, Kang L, Huang W, Jin M . Multifunctional oral delivery systems for enhanced bioavailability of therapeutic peptides/proteins. Acta Pharm Sin B. 2019; 9(5):902-922. PMC: 6804447. DOI: 10.1016/j.apsb.2019.01.004. View

Zhou P, Yang X, Wang X, Hu B, Zhang L, Zhang W . A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579(7798):270-273. PMC: 7095418. DOI: 10.1038/s41586-020-2012-7. View

Gao J, Lu G, Qi J, Li Y, Wu Y, Deng Y . Structure of the fusion core and inhibition of fusion by a heptad repeat peptide derived from the S protein of Middle East respiratory syndrome coronavirus. J Virol. 2013; 87(24):13134-40. PMC: 3838252. DOI: 10.1128/JVI.02433-13. View

Gunasekera S, Muhammad T, Stromstedt A, Rosengren K, Goransson U . Backbone Cyclization and Dimerization of LL-37-Derived Peptides Enhance Antimicrobial Activity and Proteolytic Stability. Front Microbiol. 2020; 11:168. PMC: 7046553. DOI: 10.3389/fmicb.2020.00168. View

Ashraf U, Abokor A, Edwards J, Waigi E, Royfman R, Hasan S . SARS-CoV-2, ACE2 expression, and systemic organ invasion. Physiol Genomics. 2020; 53(2):51-60. PMC: 7900915. DOI: 10.1152/physiolgenomics.00087.2020. View

Wrapp D, Wang N, Corbett K, Goldsmith J, Hsieh C, Abiona O . Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020; 367(6483):1260-1263. PMC: 7164637. DOI: 10.1126/science.abb2507. View

Zhu Y, Yu D, Yan H, Chong H, He Y . Design of Potent Membrane Fusion Inhibitors against SARS-CoV-2, an Emerging Coronavirus with High Fusogenic Activity. J Virol. 2020; 94(14). PMC: 7343218. DOI: 10.1128/JVI.00635-20. View

Jenssen H, Aspmo S . Serum stability of peptides. Methods Mol Biol. 2008; 494:177-86. DOI: 10.1007/978-1-59745-419-3_10. View

10.

Huang S . Comprehensive assessment of flexible-ligand docking algorithms: current effectiveness and challenges. Brief Bioinform. 2017; 19(5):982-994. DOI: 10.1093/bib/bbx030. View

11.

Frenck Jr R, Klein N, Kitchin N, Gurtman A, Absalon J, Lockhart S . Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents. N Engl J Med. 2021; 385(3):239-250. PMC: 8174030. DOI: 10.1056/NEJMoa2107456. View

12.

Kumar V, Taylor N, Shi S, Wickremasinghe N, DSouza R, Hartgerink J . Self-assembling multidomain peptides tailor biological responses through biphasic release. Biomaterials. 2015; 52:71-8. PMC: 4613801. DOI: 10.1016/j.biomaterials.2015.01.079. View

13.

Yuan K, Yi L, Chen J, Qu X, Qing T, Rao X . Suppression of SARS-CoV entry by peptides corresponding to heptad regions on spike glycoprotein. Biochem Biophys Res Commun. 2004; 319(3):746-52. PMC: 7111000. DOI: 10.1016/j.bbrc.2004.05.046. View

14.

Bosch B, Martina B, van der Zee R, Lepault J, Haijema B, Versluis C . Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition using spike protein heptad repeat-derived peptides. Proc Natl Acad Sci U S A. 2004; 101(22):8455-60. PMC: 420415. DOI: 10.1073/pnas.0400576101. View

15.

Maas M, Hintzen J, Loffler P, Mecinovic J . Targeting SARS-CoV-2 spike protein by stapled hACE2 peptides. Chem Commun (Camb). 2021; 57(26):3283-3286. DOI: 10.1039/d0cc08387a. View

16.

Jeong W, Lee M, Lim Y . Helix stabilized, thermostable, and protease-resistant self-assembled peptide nanostructures as potential inhibitors of protein-protein interactions. Biomacromolecules. 2013; 14(8):2684-9. DOI: 10.1021/bm400532y. View

17.

Han D, Penn-Nicholson A, Cho M . Identification of critical determinants on ACE2 for SARS-CoV entry and development of a potent entry inhibitor. Virology. 2006; 350(1):15-25. PMC: 7111894. DOI: 10.1016/j.virol.2006.01.029. View

18.

Renukuntla J, Vadlapudi A, Patel A, Boddu S, Mitra A . Approaches for enhancing oral bioavailability of peptides and proteins. Int J Pharm. 2013; 447(1-2):75-93. PMC: 3680128. DOI: 10.1016/j.ijpharm.2013.02.030. View

19.

Stromstedt A, Pasupuleti M, Schmidtchen A, Malmsten M . Evaluation of strategies for improving proteolytic resistance of antimicrobial peptides by using variants of EFK17, an internal segment of LL-37. Antimicrob Agents Chemother. 2008; 53(2):593-602. PMC: 2630634. DOI: 10.1128/AAC.00477-08. View

20.

Xia S, Liu M, Wang C, Xu W, Lan Q, Feng S . Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion. Cell Res. 2020; 30(4):343-355. PMC: 7104723. DOI: 10.1038/s41422-020-0305-x. View