Virus Genes

pp 1–8 | Cite as

In vitro antiviral activity of Griffithsin against porcine epidemic diarrhea virus

  • Lan Li
  • Xiaoming Yu
  • Haoming Zhang
  • Haiwei Cheng
  • Liting Hou
  • Qisheng ZhengEmail author
  • Jibo HouEmail author


Griffithsin is a lectin with potent antiviral activity against enveloped viruses. The objective of this study was to assess Griffithsin’s inhibitory effect on porcine epidemic diarrhea virus (PEDV). The results showed that Griffithsin reduced PEDV infection of Vero cells by approximately 82.8%. Moreover, using time-of-addition assays and RT-qPCR, we found that delayed addition of Griffithsin had a weaker inhibitory effect on PEDV than earlier treatment. The mechanism of Griffithsin’s action against PEDV involved both preventing viral attachment to host cells and disrupting cell-to-cell transmission; its dual mode of action distinguished Griffithsin from most other antiviral drugs. In conclusion, Griffithsin was identified as a potent PEDV inhibitor and may represent a candidate drug for preventing PEDV infection.


Griffithsin Antiviral Porcine epidemic diarrhea virus Lectin 



This study was supported by grants from the Special Fund for Agro-scientific Research in the Public Interest (No. 201303046) and the National Natural Science Foundation of China (No. 31772701 and No. 31502105).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

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


  1. 1.
    Mori T, O’Keefe BR, Sowder RC, Bringans S, Gardella R, Berg S, Cochran P, Turpin JA, Buckheit RW Jr, McMahon JB, Boyd MR (2005) Isolation and characterization of Griffithsin, a novel HIV-inactivating protein, from the red alga Griffithsia sp. J Biol Chem 280(10):9345–9353CrossRefGoogle Scholar
  2. 2.
    Lusvarghi S, Bewley CA (2016) Griffithsin: an antiviral lectin with outstanding therapeutic potential. Viruses 8(10):296CrossRefGoogle Scholar
  3. 3.
    Xue J (2014) Investigation of the mechanism of griffithsin (GRFT): a potent HIV entry inhibitor. Dissertations & Theses—GradworksGoogle Scholar
  4. 4.
    Ziolkowska N, O’Keefe BR, Mori T, Zhu C, Giomarelli B, Vojdani F, Palmer K, McMahon JB, Wlodawer A (2006) Domain-swapped structure of the potent antiviral protein griffithsin and its mode of carbohydrate binding. Structure 14(7):1127CrossRefGoogle Scholar
  5. 5.
    Millet JK, Séron K, Labitt RN, Danneels A, Palmer KE, Whittaker GR, Dubuisson J, Belouzard S (2016) Middle East respiratory syndrome coronavirus infection is inhibited by griffithsin. Antiviral Res 133:1CrossRefGoogle Scholar
  6. 6.
    Takebe Y, Saucedo CJ, Lund G, Uenishi R, Hase S, Tsuchiura T, Kneteman N, Ramessar K, Tyrrell DL, Shirakura M (2013) Antiviral lectins from red and blue-green algae show potent in vitro and in vivo activity against hepatitis C virus. PLoS ONE 8(5):e64449CrossRefGoogle Scholar
  7. 7.
    Nixon B, Stefanidou M, Mesquita PM, Fakioglu E, Segarra T, Rohan L, Halford W, Palmer KE, Herold BC (2013) Griffithsin protects mice from genital herpes by preventing cell-to-cell spread. J Virol 87(11):6257–6269CrossRefGoogle Scholar
  8. 8.
    Ishag HZ, Li C, Wang F, Mao X (2016) Griffithsin binds to the glycosylated proteins (E and prM) of Japanese encephalitis virus and inhibit its infection. Virus Res 215:50–54CrossRefGoogle Scholar
  9. 9.
    Ishag HZA, Li C, Huang L, Sun MX, Wang F, Ni B, Malik T, Chen PY, Mao X (2013) Griffithsin inhibits Japanese encephalitis virus infection in vitro and in vivo. Arch Virol 158(2):349–358CrossRefGoogle Scholar
  10. 10.
    Levendosky K, Mizenina O, Martinelli E, Jeanpierre N, Kizima L, Rodriguez A, Kleinbeck K, Bonnaire T, Robbiani M, Zydowsky TM (2015) Griffithsin and carrageenan combination to target herpes simplex virus 2 and human papillomavirus. Antimicrob Agents Chemother 59(12):7290–7298CrossRefGoogle Scholar
  11. 11.
    Kouokam JC, Huskens D, Schols D, Johannemann A, Riedell SK, Walter W, Walker JM, Matoba N, O’Keefe BR, Palmer KE (2011) Investigation of griffithsin’s interactions with human cells confirms its outstanding safety and efficacy profile as a microbicide candidate. PLoS ONE 6(8):e22635CrossRefGoogle Scholar
  12. 12.
    Fuqua JL, Wanga V, Palmer KE (2015) Improving the large scale purification of the HIV microbicide, griffithsin. BMC Biotechnol 15(1):12CrossRefGoogle Scholar
  13. 13.
    Moncla BJ, Pryke K, Rohan LC, Graebing PW (2011) Degradation of naturally occurring and engineered antimicrobial peptides by proteases. Adv Biosci Biotechnol 2(6):404–408CrossRefGoogle Scholar
  14. 14.
    Diel DG, Lawson S, Okda F, Singrey A, Clement T, Fernandes MH, Christopher-Hennings J, Nelson EA (2016) Porcine epidemic diarrhea virus: an overview of current virological and serological diagnostic methods. Virus Res 226:60–70CrossRefGoogle Scholar
  15. 15.
    Wang D, Fang L, Xiao S (2016) Porcine epidemic diarrhea in China. Virus Res 226:7–13CrossRefGoogle Scholar
  16. 16.
    Li HJ, Gao DS, Li YT, Wang YS, Liu HY, Zhao J (2018) Antiviral effect of lithium chloride on porcine epidemic diarrhea virus in vitro. Res Vet Sci 118:288–294CrossRefGoogle Scholar
  17. 17.
    Lee C (2015) Porcine epidemic diarrhea virus: an emerging and re-emerging epizootic swine virus. Virol J 12(1):1–16CrossRefGoogle Scholar
  18. 18.
    Hwajung C, Jinhee K, Choonghwan L, Youngjoon A, Song JH, Seunghwa B, Durhan K (2009) Antiviral activity of quercetin 7-rhamnoside against porcine epidemic diarrhea virus. Antiviral Res 81(1):77–81CrossRefGoogle Scholar
  19. 19.
    Yang Q, Gao L, Si J, Sun Y, Liu J, Cao L, Feng WH (2013) Inhibition of porcine reproductive and respiratory syndrome virus replication by flavaspidic acid AB. Antiviral Res 97(1):66–73CrossRefGoogle Scholar
  20. 20.
    Keirstead ND, Lee C, Yoo D, Brooks AS, Hayes MA (2008) Porcine plasma ficolin binds and reduces infectivity of porcine reproductive and respiratory syndrome virus (PRRSV) in vitro. Antiviral Res 77(1):28–38CrossRefGoogle Scholar
  21. 21.
    Zhu P, Liu J, Bess J, Chertova E, Lifson JD, Grisé H, Ofek GA, Taylor KA, Roux KH (2006) Distribution and three-dimensional structure of AIDS virus envelope spikes. Nature 441(7095):847–852CrossRefGoogle Scholar
  22. 22.
    Yamaguchi M, Danev R, Nishiyama K, Sugawara K, Nagayama K (2008) Zernike phase contrast electron microscopy of ice-embedded influenza A virus. J Struct Biol 162(2):271–276Google Scholar
  23. 23.
    Sougrat R, Bartesaghi A, Lifson JD, Bennett AE, Bess JW, Zabransky DJ, Subramaniam S (2007) Electron tomography of the contact between T cells and SIV/HIV-1: implications for viral entry. PLoS Pathog 3(5):e63Google Scholar
  24. 24.
    O’Keefe BR, Giomarelli B, Barnard DL, Shenoy SR, Chan PKS, Mcmahon JB, Palmer KE, Barnett BW, Meyerholz DK, Wohlfordlenane CL (2010) Broad-spectrum in vitro activity and in vivo efficacy of the antiviral protein griffithsin against emerging viruses of the family Coronaviridae. J Virol 84(5):2511–2521CrossRefGoogle Scholar
  25. 25.
    Meuleman P, Albecka A, Belouzard S, Vercauteren K, Verhoye L, Wychowski C, Lerouxroels G, Palmer KE, Dubuisson J (2011) Griffithsin has antiviral activity against hepatitis C virus. Antimicrob Agents Chemother 55(11):5159–5167CrossRefGoogle Scholar
  26. 26.
    Barton C, Kouokam J, Hurst H, Palmer K (2016) Pharmacokinetics of the antiviral lectin griffithsin administered by different routes indicates multiple potential uses. Viruses 8(12):331CrossRefGoogle Scholar
  27. 27.
    Barton C, Kouokam JC, Lasnik AB, Foreman O, Cambon A, Brock G, Montefiori DC, Vojdani F, Mccormick AA, O’Keefe BR (2014) Activity of and effect of subcutaneous treatment with the broad-spectrum antiviral lectin griffithsin in two laboratory rodent models. Antimicrob Agents Chemother 58(1):120–127CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.National Research Center of Engineering and Technology for Veterinary BiologicalsJiangsu Academy of Agricultural SciencesNanjingChina
  2. 2.Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and ZoonosesYangzhouChina

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