Skip to main content

Advertisement

SpringerLink
Log in

Role of marine natural products in the development of antiviral agents against SARS-CoV-2: potential and prospects

  • Review
  • Published:
Marine Life Science & Technology Aims and scope Submit manuscript

Abstract

A novel coronavirus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has surfaced and caused global concern owing to its ferocity. SARS-CoV-2 is the causative agent of coronavirus disease 2019; however, it was only discovered at the end of the year and was considered a pandemic by the World Health Organization. Therefore, the development of novel potent inhibitors against SARS-CoV-2 and future outbreaks is urgently required. Numerous naturally occurring bioactive substances have been studied in the clinical setting for diverse disorders. The intricate infection and replication mechanism of SARS-CoV-2 offers diverse therapeutic drug targets for developing antiviral medicines by employing natural products that are safer than synthetic compounds. Marine natural products (MNPs) have received increased attention in the development of novel drugs owing to their high diversity and availability. Therefore, this review article investigates the infection and replication mechanisms, including the function of the SARS-CoV-2 genome and structure. Furthermore, we highlighted anti-SARS-CoV-2 therapeutic intervention efforts utilizing MNPs and predicted SARS-CoV-2 inhibitor design.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The data that support the findings of this study are included in this published article (and its supplementary information files).

References

  • Aatif M, Muteeb G, Alsultan A, Alshoaibi A, Khelif BY (2021) Dieckol and its derivatives as potential inhibitors of SARS-CoV-2 spike protein (UK strain: VUI 202012/01): a computational study. Mar Drugs 19:242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anand K, Ziebuhr J, Wadhwani P, Mesters JR, Hilgenfeld R (2003) Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs. Science 300:1763–1767

    Article  ADS  CAS  PubMed  Google Scholar 

  • Anderson ED, Thomas L, Hayflick JS, Thomas G (1993) Inhibition of HIV-1 gp160-dependent membrane fusion by a furin-directed alpha 1-antitrypsin variant. J Biol Chem 268:24887–24891

    Article  CAS  PubMed  Google Scholar 

  • Anjum K, Abbas SQ, Shah SA, Akhter N, Batool S, Hassan SS (2016) Marine sponges as a drug treasure. Biomol Ther (seoul) 24:347–362

    Article  CAS  PubMed  Google Scholar 

  • Astuti I, Ysrafil Y (2020) Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response. Diabetes Metab Syndr 14:407–412

    Article  PubMed  PubMed Central  Google Scholar 

  • Baez-Santos YM, St John SE, Mesecar AD (2015) The SARS-coronavirus papain-like protease: structure, function and inhibition by designed antiviral compounds. Antivir Res 115:21–38

    Article  CAS  PubMed  Google Scholar 

  • Békés M, Rut W, Kasperkiewicz P, Mulder MPC, Ovaa H, Drag M, Lima CD, Huang TT (2015) SARS hCoV papain-like protease is a unique Lys48 linkage-specific di-distributive deubiquitinating enzyme. Biochem J 468:215–226

    Article  PubMed  Google Scholar 

  • Belouzard S, Millet JK, Licitra BN, Whittaker GR (2012) Mechanisms of coronavirus cell entry mediated by the viral spike protein. Viruses 4:1011–1033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bergmann W, Feeney RJ (2002) Contributions to the study of marine products. Xxxii. The Nucleosides of Sponges. I.1. J Org Chem 16:981–987

    Article  Google Scholar 

  • Berlin DA, Gulick RM, Martinez FJ (2020) Severe covid-19. N Engl J Med 383:2451–2460

    Article  CAS  PubMed  Google Scholar 

  • Bestle D, Heindl MR, Limburg H, Van Lam T, Pilgram O, Moulton H, Stein DA, Hardes K, Eickmann M, Dolnik O, Rohde C, Klenk H, Garten W, Steinmetzer T, Bottcher-Friebertshauser E (2020) TMPRSS2 and furin are both essential for proteolytic activation of SARS-CoV-2 in human airway cells. Life Sci Alliance 3:e202000786

    Article  PubMed  PubMed Central  Google Scholar 

  • Bolles M, Donaldson E, Baric R (2011) SARS-CoV and emergent coronaviruses: viral determinants of interspecies transmission. Curr Opin Virol 1:624–634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bosch BJ, van der Zee R, de Haan CA, Rottier PJ (2003) The coronavirus spike protein is a class I virus fusion protein: structural and functional characterization of the fusion core complex. J Virol 77:8801–8811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bruno BJ, Miller GD, Lim CS (2013) Basics and recent advances in peptide and protein drug delivery. Ther Deliv 4:1443–1467

    Article  CAS  PubMed  Google Scholar 

  • Buchanan MS, Carroll AR, Wessling D, Jobling M, Avery VM, Davis RA, Feng Y, Xue Y, Öster L, Fex T, Deinum J, Hooper JNA, Quinn RJ (2008) Clavatadine A, a natural product with selective recognition and irreversible inhibition of factor XIa. J Med Chem 51:3583–3587

    Article  CAS  PubMed  Google Scholar 

  • Bugge TH, Antalis TM, Wu Q (2009) Type II transmembrane serine proteases. J Biol Chem 284:23177–23181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bzowka M, Mitusinska K, Raczynska A, Samol A, Tuszynski JA, Gora A (2020) Structural and evolutionary analysis indicate that the SARS-CoV-2 Mpro is a challenging target for small-molecule inhibitor design. Int J Mol Sci 21:3099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yun Y et al (2020) A trial of lopinavir-ritonavir in adults hospitalized with severe covid-19. N Engl J Med 382:1787–1799

    Article  PubMed  Google Scholar 

  • Chen Y, Liu Q, Guo D (2020) Emerging coronaviruses: genome structure, replication, and pathogenesis. J Med Virol 92:418–423

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Damonte EB, Matulewicz MC, Cerezo AS (2004) Sulfated seaweed polysaccharides as antiviral agents. Curr Med Chem 11:2399–2419

    Article  CAS  PubMed  Google Scholar 

  • Devi KP, Pourkarim MR, Thijssen M, Sureda A, Khayatkashani M, Cismaru CA, Neagoe IB, Habtemariam S, Razmjouei S, Khayat Kashani HR (2022) A perspective on the applications of furin inhibitors for the treatment of SARS-CoV-2. Pharmacol Rep 74:425–430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Donaldson SH, Hirsh A, Li DC, Holloway G, Chao J, Boucher RC, Gabriel SE (2002) Regulation of the epithelial sodium channel by serine proteases in human airways. J Biol Chem 277:8338–8345

    Article  CAS  PubMed  Google Scholar 

  • Donia M, Hamann MT (2003) Marine natural products and their potential applications as anti-infective agents. Lancet Infect Dis 3:338–348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Du QS, Wang SQ, Zhu Y, Wei DQ, Guo H, Sirois S, Chou KC (2004) Polyprotein cleavage mechanism of SARS CoV Mpro and chemical modification of the octapeptide. Peptides 25:1857–1864

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Du L, He Y, Zhou Y, Liu S, Zheng BJ, Jiang S (2009) The spike protein of SARS-CoV—a target for vaccine and therapeutic development. Nat Rev Microbiol 7:226–236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dufour EK, Denault JB, Bissonnette L, Hopkins PC, Lavigne P, Leduc R (2001) The contribution of arginine residues within the P6–P1 region of alpha 1-antitrypsin to its reaction with furin. J Biol Chem 276:38971–38979

    Article  CAS  PubMed  Google Scholar 

  • Dzimianski JV, Scholte FEM, Bergeron E, Pegan SD (2019) ISG15: It’s complicated. J Mol Biol 431:4203–4216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • EA JA, Jones IM (2019) Membrane binding proteins of coronaviruses. Future Virol 14:275–286

    Article  Google Scholar 

  • Ersmark K, Del Valle JR, Hanessian S (2008) Chemistry and biology of the aeruginosin family of serine protease inhibitors. Angew Chem Int Ed Engl 47:1202–1223

    Article  CAS  PubMed  Google Scholar 

  • Ferrer-Orta C, Arias A, Escarmis C, Verdaguer N (2006) A comparison of viral RNA-dependent RNA polymerases. Curr Opin Struct Biol 16:27–34

    Article  CAS  PubMed  Google Scholar 

  • Finkel Y, Mizrahi O, Nachshon A, Weingarten-Gabbay S, Morgenstern D, Yahalom-Ronen Y, Tamir H, Achdout H, Stein D, Israeli O, Beth-Din A, Melamed S, Weiss S, Israely T, Paran N, Schwartz M, Stern-Ginossar N (2021) The coding capacity of SARS-CoV-2. Nature 589:125–130

    Article  ADS  CAS  PubMed  Google Scholar 

  • Firdaus M, Nurdiani R, Artasasta IN, Mutoharoh S, Pratiwi O (2020) Potency of three brown seaweeds species as the inhibitor of RNA-dependent RNA polymerase of SARS-CoV-2. Rev Chim 71:80–86

    Article  CAS  Google Scholar 

  • Frieman M, Baric R (2008) Mechanisms of severe acute respiratory syndrome pathogenesis and innate immunomodulation. Microbiol Mol Biol Rev 72:672–685

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fu Z, Huang B, Tang J, Liu S, Liu M, Ye Y, Liu Z, Xiong Y, Zhu W, Cao D, Li J, Niu X, Zhou H, Zhao YJ, Zhang G, Huang H (2021) The complex structure of GRL0617 and SARS-CoV-2 PLpro reveals a hot spot for antiviral drug discovery. Nat Commun 12:488

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao Y, Yan L, Huang Y, Liu F, Zhao Y, Cao L, Wang T, Sun Q, Ming Z, Zang L, Ge J, Zheng L, Zhang Y, Wang H, Zhu Y, Zhu C, Hu T, Hua T, Zhang B, Yang X et al (2020) Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science 368:779–782

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, Doudier B, Courjon J, Giordanengo V, Viera VE, Dupont HT, Honoré S, Colson P, Chabrière E, Scola B, Rolanin J, Brouqui P, Raoult D (2020) Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents 56:105949

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gentile D, Patamia V, Scala A, Sciortino MT, Piperno A, Rescifina A (2020) Putative inhibitors of SARS-CoV-2 main protease from a library of marine natural products: a virtual screening and molecular modeling study. Mar Drugs 18:225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gonzalez Y, Doens D, Santamaria R, Ramos M, Restrepo CM, Barros de Arruda L, Lleonart R, Gutiérrez M, Fernandez PL (2013) A pseudopterane diterpene isolated from the octocoral Pseudopterogorgia acerosa inhibits the inflammatory response mediated by TLR-ligands and TNF-alpha in macrophages. PLoS ONE 8:e84107

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  • Graham RL, Baric RS (2020) SARS-CoV-2: combating coronavirus emergence. Immunity 52:734–736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gui M, Song W, Zhou H, Xu J, Chen S, Xiang Y, Wang X (2017) Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding. Cell Res 27:119–129

    Article  CAS  PubMed  Google Scholar 

  • Hasoksuz M, Sreevatsan S, Cho KO, Hoet AE, Saif LJ (2002) Molecular analysis of the S1 subunit of the spike glycoprotein of respiratory and enteric bovine coronavirus isolates. Virus Res 84:101–109

    Article  CAS  PubMed  Google Scholar 

  • Heald-Sargent T, Gallagher T (2012) Ready, set, fuse! The coronavirus spike protein and acquisition of fusion competence. Viruses 4:557–580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heaton SM, Borg NA, Dixit VM (2016) Ubiquitin in the activation and attenuation of innate antiviral immunity. J Exp Med 213:1–13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, Schiergens TS, Herrier G, Wu NH, Nitsche A, Muller MA, Pohlmann S (2020) SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181:271–280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hofmann H, Hattermann K, Marzi A, Gramberg T, Geier M, Krumbiegel M, Kuate S, Uberia K, Niedrig M, Pohlmann S (2004) S protein of severe acute respiratory syndrome-associated coronavirus mediates entry into hepatoma cell lines and is targeted by neutralizing antibodies in infected patients. J Virol 78:6134–6142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hung IF, Lung KC, Tso EY, Liu R, Chung TW, Chu MY, Ng YY, Lo J, Chan J, Tan AR, Shum HP, Chan V, Ku AK, Sin KM, Leung WS, Law WL, Lung DC, Sin S, Yeung P, Yip CC et al (2020) Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet 395:1695–1704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Imran M, Saleemi MK, Chen Z, Wang XG, Zhou DY, Li YC, Zhao Z, Zheng B, Li Q, Cao S, Ye J (2019) Decanoyl-Arg-Val-Lys-Arg-Chloromethylketone: an antiviral compound that acts against flaviviruses through the inhibition of furin-mediated prM cleavage. Viruses-Basel 11:1011

    Article  CAS  Google Scholar 

  • Ireland CM, Copp BR, Foster MP, McDonald LA, Radisky DC, Swersey JC (2000) Bioactive compounds from the sea Marine and freshwater products handbook. CRC Press, Boca Raton, pp 641–661

    Google Scholar 

  • Iwata-Yoshikawa N, Okamura T, Shimizu Y, Hasegawa H, Takeda M, Nagata N (2019) TMPRSS2 contributes to virus spread and immunopathology in the airways of murine models after coronavirus infection. J Virol 93:e01815-01818

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jaafar ZA, Kieft JS (2019) Viral RNA structure-based strategies to manipulate translation. Nat Rev Microbiol 17:110–123

    Article  CAS  PubMed  Google Scholar 

  • Jayawardena TU, Sanjeewa KKA, Nagahawatta DP, Lee HG, Lu YA, Vaas APJP, Abeytunga DTU, Nanayakkara CM, Lee DS, Jeon YJ (2020) Anti-inflammatory effects of sulfated polysaccharide from Sargassum swartzii in macrophages via blocking TLR/NF-Κb signal transduction. Mar Drugs 18:601

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jayawardena TU, Nagahawatta DP, Fernando IPS, Kim YT, Kim JS, Kim WS, Lee JS, Jeon YJ (2022) A review on fucoidan structure, extraction techniques, and its role as an immunomodulatory agent. Mar Drugs 20:755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jean F, Stella K, Thomas L, Liu G, Xiang Y, Reason AJ, Thomas G (1998) alpha1-Antitrypsin Portland, a bioengineered serpin highly selective for furin: application as an antipathogenic agent. Proc Natl Acad Sci USA 95:7293–7298

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Jin W, Zhang W, Mitra D, McCandless MG, Sharma P, Tandon R, Zhang F, Linhardt RJ (2020) The structure-activity relationship of the interactions of SARS-CoV-2 spike glycoproteins with glucuronomannan and sulfated galactofucan from Saccharina japonica. Int J Biol Macromol 163:1649–1658

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaushik D, Bhandari R, Kuhad A (2021) TLR4 as a therapeutic target for respiratory and neurological complications of SARS-CoV-2. Expert Opin Ther Targets 25:491–508

    Article  CAS  PubMed  Google Scholar 

  • Khan MT, Ali A, Wang Q, Irfan M, Khan A, Zeb MT, Zhang YJ, Chinnasamy S, Wei DQ (2021) Marine natural compounds as potents inhibitors against the main protease of SARS-CoV-2-a molecular dynamic study. J Biomol Struct Dyn 39:3627–3637

    Article  CAS  PubMed  Google Scholar 

  • Kim TS, Heinlein C, Hackman RC, Nelson PS (2006) Phenotypic analysis of mice lacking the Tmprss2-encoded protease. Mol Cell Biol 26:965–975

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim SY, Jin W, Sood A, Montgomery DW, Grant OC, Fuster MM, Fu L, Dordick JS, Woods R, Zhang F, Linhardt RJ (2020) Characterization of heparin and severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) spike glycoprotein binding interactions. Antivir Res 181:104873

    Article  CAS  PubMed  Google Scholar 

  • Klemm T, Ebert G, Calleja DJ, Allison CC, Richardson LW, Bernardini JP, Lu BG, Kuchei NW, Grohmann C, Shibata Y, Gan ZY, Cooney JP, Doerflinger M, Au AE, Blackmore TR, Noort GJ, Geurink PP, Ovaa H, Newman J, Tunnicliffe AR et al (2020) Mechanism and inhibition of the papain-like protease, PLpro, of SARS-CoV-2. EMBO J 39:e106275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ko W, Sohn JH, Jang JH, Ahn JS, Kang DG, Lee HS, Kim JS, Kim YC, Oh H (2016) Inhibitory effects of alternaramide on inflammatory mediator expression through TLR4-MyD88-mediated inhibition of NF-small ka, CyrillicB and MAPK pathway signaling in lipopolysaccharide-stimulated RAW264.7 and BV2 cells. Chem Biol Interact 244:16–26

    Article  CAS  PubMed  Google Scholar 

  • König GM, Wright AD, Sticher O, Angerhofer CK, Pezzuto JMJPM (1994) Biological activities of selected marine natural products. Planta Med 60:532–537

    Article  PubMed  Google Scholar 

  • Kumar V, Parate S, Yoon S, Lee G, Lee KW (2021) Computational simulations identified marine-derived natural bioactive compounds as replication inhibitors of SARS-CoV-2. Front Microbiol 12:647295–647295

    Article  PubMed  PubMed Central  Google Scholar 

  • Kupferschmidt K, Cohen J (2020) Race to find COVID-19 treatments accelerates. Science 367:1412–1413

    Article  ADS  CAS  PubMed  Google Scholar 

  • Kwon PS, Oh H, Kwon SJ, Jin W, Zhang F, Fraser K, Hong JJ, Linhard RJ, Dordick JS (2020) Sulfated polysaccharides effectively inhibit SARS-CoV-2 in vitro. Cell Discov 6:50

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Letko M, Marzi A, Munster V (2020) Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol 5:562–569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li F (2013) Receptor recognition and cross-species infections of SARS coronavirus. Antivir Res 100:246–254

    Article  CAS  PubMed  Google Scholar 

  • Li F (2015) Receptor recognition mechanisms of coronaviruses: a decade of structural studies. J Virol 89:1954–1964

    Article  PubMed  Google Scholar 

  • Li F (2016) Structure, function, and evolution of coronavirus spike proteins. Annu Rev Virol 3:237–261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M (2003) Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 426:450–454

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Li F, Li W, Farzan M, Harrison SC (2005) Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science 309:1864–1868

    Article  ADS  CAS  PubMed  Google Scholar 

  • Lim L, Shi J, Mu Y, Song JJPO (2014) Dynamically-driven enhancement of the catalytic machinery of the SARS 3C-like protease by the S284–T285-I286/A mutations on the extra domain. PLoS ONE 9:e101941

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  • Lindahl U, Li JP (2020) Heparin - an old drug with multiple potential targets in Covid-19 therapy. J Thromb Haemost 18:2422–2424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lindahl U, Couchman J, Kimata K, Esko JD (2015) Proteoglycans and sulfated glycosaminoglycans, 3rd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor

    Google Scholar 

  • Lu R, Wang Y, Wang W, Nie K, Deng Y, Zhou W, Li Y, Wang H, Wang W, Ke C, Ma X, Wu G, Tan W (2015) Complete genome sequence of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) from the first imported MERS-CoV Case in China. Genome Announc 3:e00818-e1815

    Article  PubMed  PubMed Central  Google Scholar 

  • Mayer AMS, Rodríguez AD, Berlinck RGS, Fusetani N (2011) Marine pharmacology in 2007–8: marine compounds with antibacterial, anticoagulant, antifungal, anti-inflammatory, antimalarial, antiprotozoal, antituberculosis, and antiviral activities; affecting the immune and nervous system, and other miscellaneous mechanisms of action. Comp Biochem Physiol Part C Toxicol Appl Pharmacol 153:191–222

    Article  Google Scholar 

  • Merad M, Martin JC (2020) Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat Rev Immunol 20:355–362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller B, Friedman AJ, Choi H, Hogan J, McCammon JA, HookV GWH (2014) The marine cyanobacterial metabolite gallinamide A is a potent and selective inhibitor of human cathepsin L. J Nat Prod 77:92–99

    Article  CAS  PubMed  Google Scholar 

  • Morse JS, Lalonde T, Xu S, Liu WR (2020) Learning from the past: possible urgent prevention and treatment options for severe acute respiratory infections caused by 2019-nCoV. Chembiocehm 21:730–738

    Article  CAS  Google Scholar 

  • Muller C, Schulte FW, Lange-Grunweller K, Obermann W, Madhugiri R, Pleschka S, Ziebuhr J, Hartmann RK, Grunweller A (2018) Broad-spectrum antiviral activity of the eIF4A inhibitor silvestrol against corona- and picornaviruses. Antivir Res 150:123–129

    Article  PubMed  Google Scholar 

  • Nagahawatta DP, Kim HS, Jee Y-H, Jayawardena TU, Ahn G, Namgung J, Yeo I, Sanjeewa KKA, Jeon YJ (2022a) Sargachromenol isolated from Sargassum horneri inhibits particulate matter-induced inflammation in macrophages through toll-like receptor-mediated cell signaling pathways. Mar Drugs 20:28

    Article  CAS  Google Scholar 

  • Nagahawatta DP, Liyanage NM, Jayawardhana HHACK, Jayawardena TU, Lee HG, Heo MS, Jeon YJ (2022b) Eckmaxol isolated from Ecklonia maxima attenuates particulate-matter-induced inflammation in MH-S lung macrophage. Mar Drugs 20:766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagahawatta DP, Liyanage NM, Jayawardhana HHACK, Lee HG, Jayawardena TU, Jeon YJ (2022c) Anti-fine dust effect of fucoidan extracted from Ecklonia maxima laves in macrophages via inhibiting inflammatory signaling pathways. Mar Drugs 20:413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagahawatta DP, Liyanage NM, Je JG, Jayawardhana HHACK, Jayawardena TU, Jeong SH, Kwon HJ, Choi CS, Jeon YJ (2022d) Polyphenolic compounds isolated from marine algae attenuate the replication of SARS-CoV-2 in the host cell through a multi-target approach of 3CLpro and PLpro. Mar Drugs 20:786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakao Y, Masuda A, Matsunaga S, Fusetani N (1999) Pseudotheonamides, serine protease inhibitors from the marine sponge Theonella swinhoei 1. J Am Chem Soc 121:2425–2431

    Article  CAS  Google Scholar 

  • Naqvi AAT, Fatima K, Mohammad T, Fatima U, Singh IK, Singh A, Atif SM, Hariprasad G, Hasan GM, Hassan MI (2020) Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: structural genomics approach. Biochim Biophys Acta Mol Basis Dis 1866:165878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neculai D, Schwake M, Ravichandran M, Zunke F, Collins RF, Peters J, Neculai M, Plumb J, Loppnau P, Pizarro JC, Seitova A, Trimble WS, Saftig P, Grinstein S, Dhe-Paganon S (2013) Structure of LIMP-2 provides functional insights with implications for SR-BI and CD36. Nature 504:172–176

    Article  ADS  CAS  PubMed  Google Scholar 

  • Neuman BW, Kiss G, Kunding AH, Bhella D, Baksh MF, Connelly S, Droese B, Klaus JP, Makino S, Sawicki SG, Siddell SG, Stamou DG, Wilson IA, Kuhun P, Buchmeier MJ (2011) A structural analysis of M protein in coronavirus assembly and morphology. J Struct Biol 174:11–22

    Article  CAS  PubMed  Google Scholar 

  • Ogden KM, Ramanathan HN, Patton JT (2012) Mutational analysis of residues involved in nucleotide and divalent cation stabilization in the rotavirus RNA-dependent RNA polymerase catalytic pocket. Virology 431:12–20

    Article  CAS  PubMed  Google Scholar 

  • Ou X, Liu Y, Lei X, Li P, Mi D, Ren L, Guo L, Guo R, Chen T, Hu J, Xiang Z, Mu Z, Chen X, Chen J, Hu K, Jin Q, Wang J, Qian Z (2020) Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun 11:1620

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Park JY, Kim JH, Kwon JM, Kwon HJ, Jeong HJ, Kim YM, Kim D, Lee WS, Ryu YB (2013) Dieckol, a SARS-CoV 3CL(pro) inhibitor, isolated from the edible brown algae Ecklonia cava. Bioorg Med Chem 21:3730–3737

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pavlicevic M, Maestri E, Marmiroli M (2020) Marine bioactive peptides-an overview of generation, structure and application with a focus on food sources. Mar Drugs 18:424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pereira L, Critchley AT (2020) The COVID 19 novel coronavirus pandemic 2020: seaweeds to the rescue? Why does substantial, supporting research about the antiviral properties of seaweed polysaccharides seem to go unrecognized by the pharmaceutical community in these desperate times? J Appl Phycol 32:1875–1877

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perlman S, Netland J (2009) Coronaviruses post-SARS: update on replication and pathogenesis. Nat Rev Microbiol 7:439–450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pillaiyar T, Manickam M, Namasivayam V, Hayashi Y, Jung SH (2016) An overview of Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV) 3CL protease inhibitors: peptidomimetics and small molecule chemotherapy. J Med Chem 59:6595–6628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pomponi SA (1999) The bioprocess-technological potential of the sea. In: Osinga R, Tramper J, Burgess JG, Wijffels RH (eds) Progress in industrial microbiology, vol 35. Elsevier, Amsterdam, pp 5–13

    Google Scholar 

  • Rota PA, Oberste MS, Monroe SS, Nix WA, Campagnoli R, Icenogle JP, Penaranda S, Bankamp B, Maher K, Chen MH, Tong S, Tamin A, Lowe L, Frace M, Derisi JL, Chen Q, Wang D, Erdman DD, Peret TC, Burns C et al (2003) Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science 300:1394–1399

    Article  ADS  CAS  PubMed  Google Scholar 

  • Sanjeewa KKA, Kim EA, Son KT, Jeon YJ (2016) Bioactive properties and potentials cosmeceutical applications of phlorotannins isolated from brown seaweeds: a review. J Photochem Photobiol B Biol 162:100–105

    Article  CAS  Google Scholar 

  • Sanjeewa KKA, Nagahawatta DP, Yang HW, Oh JY, Jayawardena TU, Jeon YJ, Zoysa M, Whang I, Ryu B (2020) Octominin inhibits LPS-induced chemokine and pro-inflammatory cytokine secretion from RAW 264.7 macrophages via blocking TLRs/NF-κB signal transduction. Biomolecules 10:511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sariol A, Perlman S (2021) SARS-CoV-2 takes its toll. Nat Immunol 22:801–802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Satija N, Lal SK (2007) The molecular biology of SARS coronavirus. Ann N Y Acad Sci 1102:26–38

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Schoeman D, Fielding BC (2019) Coronavirus envelope protein: current knowledge. Virol J 16:69

    Article  PubMed  PubMed Central  Google Scholar 

  • Schubert K, Karousis ED, Jomaa A, Scaiola A, Echeverria B, Gurzeler LA, Leibundgut M, Thiel V, Mühlemann O, Ban N (2020) SARS-CoV-2 Nsp1 binds the ribosomal mRNA channel to inhibit translation. Nat Struct Mol Biol 27:959–966

    Article  CAS  PubMed  Google Scholar 

  • Seley-Radtke KL, Yates MK (2018) The evolution of nucleoside analogue antivirals: a review for chemists and non-chemists. Part 1: Early structural modifications to the nucleoside scaffold. Antivir Res 154:66–86

    Article  CAS  PubMed  Google Scholar 

  • Shang J, Wan Y, Luo C, Ye G, Geng Q, Auerbach A, Li F (2020a) Cell entry mechanisms of SARS-CoV-2. Proc Natl Acad Sci USA 117:11727–11734

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Shang J, Ye G, Shi K, Wan Y, Luo C, Aihara H, Geng Q, Auerabach A, Li F (2020b) Structural basis of receptor recognition by SARS-CoV-2. Nature 581:221–224

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Shen WJ, Asthana S, Kraemer FB, Azhar SJJOLR (2018a) Scavenger receptor B type 1: expression, molecular regulation, and cholesterol transport function. JLR 59:1114–1131

    CAS  Google Scholar 

  • Shen WJ, Azhar S, Kraemer FB (2018b) SR-B1: a unique multifunctional receptor for cholesterol influx and efflux. Annu Rev Physiol 80:95–116

    Article  CAS  PubMed  Google Scholar 

  • Shinde P, Banerjee P, Mandhare A (2019) Marine natural products as source of new drugs: a patent review (2015–2018). Expert Opin Ther Pat 29:283–309

    Article  CAS  PubMed  Google Scholar 

  • Simmons G, Gosalia DN, Rennekamp AJ, Reeves JD, Diamond SL, Bates P (2005) Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry. Proc Natl Acad Sci USA 102:11876–11881

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Sola I, Almazán F, Zúñiga S, Enjuanes L (2015) Continuous and discontinuous RNA synthesis in coronaviruses. Annu Rev Virol 2:265–288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song S, Peng H, Wang Q, Liu Z, Dong X, Wen C, Ai C, Zhang Y, Wang Z, Zhu B (2020) Inhibitory activities of marine sulfated polysaccharides against SARS-CoV-2. Food Funct 11:7415–7420

    Article  CAS  PubMed  Google Scholar 

  • Speake H, Phillips A, Chong T, Sikazwe C, Levy A, Lang J, Scalley B, Speers DJ, Smith DW, Effler P, McEvoy SP (2020) Flight-associated transmission of Severe Acute Respiratory Syndrome Coronavirus 2 corroborated by whole-genome sequencing. Emerg Infect Dis 26:2872–2880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steitz TA (1998) A mechanism for all polymerases. Nature 391:231–232

    Article  ADS  CAS  PubMed  Google Scholar 

  • Surti M, Patel M, Adnan M, Moin A, Ashraf SA, Siddiqui AJ, Snoussi M, Deshpande S, Reddy MNJRA (2020) Ilimaquinone (marine sponge metabolite) as a novel inhibitor of SARS-CoV-2 key target proteins in comparison with suggested COVID-19 drugs: designing, docking and molecular dynamics simulation study. RSC Adv 10:37707–37720

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Tamama K (2020) Potential benefits of dietary seaweeds as protection against COVID-19. Nutr Rev 79:814–823

    Article  Google Scholar 

  • Tang C, Deng Z, Li X, Yang M, Tian Z, Chen Z, Wang G, Wu W, Feng WH, Zhang G, Chen Z (2020) Helicase of type 2 porcine reproductive and respiratory syndrome virus strain HV reveals a unique structure. Viruses 12:215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Therapy REoC (2021) Recovery trial closes recruitment to colchicine treatment for patients hospitalised with COVID-19. https://www.recoverytrial.net/news/recovery-trial-closes-recruitment-to-colchicine-treatment-for-patients-hospitalised-with-covid-19

  • Tong TR (2009) Drug targets in severe acute respiratory syndrome (SARS) virus and other coronavirus infections. Infect Disord Drug Targets 9:223–245

    Article  CAS  PubMed  Google Scholar 

  • Ullrich S, Nitsche C (2020) The SARS-CoV-2 main protease as drug target. Bioorg Med Chem Lett 30:127377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • V’kovski P, Kratzel A, Steiner S, Stalder H, Thiel V (2021) Coronavirus biology and replication: implications for SARS-CoV-2. Nat Rev Microbiol 19:155–170

    Article  PubMed  Google Scholar 

  • Vaarala MH, Porvari KS, Kellokumpu S, Kyllönen AP, Vihko PT (2001) Expression of transmembrane serine protease TMPRSS2 in mouse and human tissues. J Pathol 193:134–140

    Article  CAS  PubMed  Google Scholar 

  • Venkataraman S, Prasad BVLS, Selvarajan R (2018) RNA dependent RNA polymerases: Insights from structure, function and evolution. Viruses 10:76

    Article  PubMed  PubMed Central  Google Scholar 

  • Walls AC, Xiong X, Park YJ, Tortorici MA, Snijder J, Quispe J, Cameroni E, Gopal R, Dai M, Lazavecchia A, Zambon M, Rey FA, Veesler D (2019) Unexpected receptor functional mimicry elucidates activation of coronavirus fusion. Cell 176:1026–1039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D (2020) Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 181:281–292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang SH, Huang CY, Chen CY, Chang CC, Huang CY, Dong CD, Chang JS (2020) Structure and biological activity analysis of fucoidan isolated from Sargassum siliquosum. ACS Omega 5:32447–32455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wei C, Wan L, Yan Q, Wang X, Zhang J, Yang X, Zhang Y, Fan C, Li D, Deng Y, Sun J, Gong J, Yang X, Wang Y, Wang X, Li J, Yang H, Li H, Zhang Z, Wang R et al (2020) HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry. Nat Metab 2:1391–1400

    Article  CAS  PubMed  Google Scholar 

  • White KM, Rosales R, Yildiz S, Kehrer T, Miorin L, Moreno E, Jangra S, Uccellini MB, Rathnesinghe R, Coughlan L, Romareo C, Batra J, Rojc A, Bouhaddou M, Fabius JM, Dejosez MD, Guillen MJ, Losada A, Aviles P, Schotsaert M et al (2021) Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A. Science 371:926–931

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Wong JP, Damania B (2021) SARS-CoV-2 dependence on host pathways. Science 371:884–885

    Article  ADS  CAS  PubMed  Google Scholar 

  • Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, Graham BS, McLellan JS (2020) Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 367:1260–1263

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, Hu Y, Tao ZW, Tian JH, Pei YY, Yuan ML, Zhang YL, Dai FH, Liu Y, Wang QM, Zheng JJ, Xu L, Holmes EC, Zhang YZ (2020) A new coronavirus associated with human respiratory disease in China. Nature 579:265–269

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu Z, Peng C, Shi Y, Zhu Z, Mu K, Wang X, Zhu W (2020) Nelfinavir was predicted to be a potential inhibitor of 2019-nCov main protease by an integrative approach combining homology modelling, molecular docking and binding free energy calculation. BioRxiv 2020.2001.2027.921627

  • Xue B, Blocquel D, Habchi J, Uversky AV, Kurgan L, Uversky VN, Longhi S (2014) Structural disorder in viral proteins. Chem Rev 114:6880–6911

    Article  CAS  PubMed  Google Scholar 

  • Yasuhara-Bell J, Lu Y (2010) Marine compounds and their antiviral activities. Antivir Res 86:231–240

    Article  CAS  PubMed  Google Scholar 

  • Yau R, Rape M (2016) The increasing complexity of the ubiquitin code. Nat Cell Biol 18:579–586

    Article  CAS  PubMed  Google Scholar 

  • Yuan Y, Cao D, Zhang Y, Ma J, Qi J, Wang Q, Lu G, Wu Y, Yan J, Shi Y, Zhang X, Gao GF (2017) Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains. Nat Commun 8:15092

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS (2020) Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med 46:586–590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou Y, Vedantham P, Lu K, Agudelo J, Carrion R Jr, Nunneley JW, Barnard D, Pöhlmann S, McKerrow JH, Reslo AR, Simmons G (2015) Protease inhibitors targeting coronavirus and filovirus entry. Antivir Res 116:76–84

    Article  CAS  PubMed  Google Scholar 

  • Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Yan Z, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jianh RD, Liu MQ, Chen Y, Shen XR, Wang X, Shuang X et al (2020) A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579:270–273

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This research was part of the project “Development of functional food products with natural materials derived from marine resources (no. 20170285)”, funded by the Ministry of Oceans and Fisheries, Korea.

Author information

Authors and Affiliations

  1. Department of Marine Life Sciences, Jeju National University, Jeju, 690-756, Republic of Korea

    D. P. Nagahawatta, N. M. Liyanage, H. H. A. C. K. Jayawardhana & You-Jin Jeon

  2. Department of Chemistry, Biochemistry and Physics, Université du Québec à Trois-Rivières, Trois-Rivières, QC, G8Z 4M3, Canada

    Thilina U. Jayawardena

  3. Marine Science Institute, Jeju National University, Jeju, 63333, Republic of Korea

    You-Jin Jeon

  4. Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup-si, Republic of Korea

    Seong-Hun Jeong & Hyung-Jun Kwon

Authors
  1. D. P. Nagahawatta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. M. Liyanage
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thilina U. Jayawardena
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. H. A. C. K. Jayawardhana
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Seong-Hun Jeong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hyung-Jun Kwon
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. You-Jin Jeon
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization, DPN and JYJ; methodology, DPN; software, DPN; validation, DPN; formal analysis, DPN; investigation, DPN; resources, DPN AND JYJ; data collection, DPN, NML, TUJ, HHACKJ, and SHJ; writing—original draft preparation, DPN; writing—review and editing, DPN, JYJ, and HJK; supervision, JYJ; project administration, JYJ; funding acquisition, JYJ. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Hyung-Jun Kwon or You-Jin Jeon.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest. Author You-Jin Jeon is one of the Editorial Board Members, but he was not involved in the journal’s review of, or decision related to, this manuscript.

Animal and human rights statement

This article does not contain any studies with human participants or animals performed by the authors.

Additional information

Edited by Chengchao Chen.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 317 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nagahawatta, D.P., Liyanage, N.M., Jayawardena, T.U. et al. Role of marine natural products in the development of antiviral agents against SARS-CoV-2: potential and prospects. Mar Life Sci Technol (2024). https://doi.org/10.1007/s42995-023-00215-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s42995-023-00215-9

Keywords

Search

Navigation