Shrimp Heparinoids as a Treatment Proposal for Severe Respiratory Disease

In addition to their wide use in anticoagulant and antithrombotic therapy, heparin and heparinoids are known to have antiviral effects. Trials are being conducted in order to evaluate their use in anticoagulant treatment for COVID-19 patients, especially those with coagulopathy [1]. The studies suggest that heparin may prevent intravascular coagulation and venous thromboembolism. Due to the potential of heparin to ameliorate severe cases of disease in patients with the novel coronavirus, shortage of heparin supply may provoke another public health issue. Some shrimp heparinoids that present novel structures and strong antithrombotic properties may be useful as alternatives without triggering hemorrhaging, a side effect of heparin, and neither thrombocytopenia, elevation of serum aminotransferases nor hyperkalemia.

Shrimp heparinoids can be extracted from industrial by-products and represent an important, but unexploited, bioproduct of the processing of this crustacea [2]. Production of cultivated and wild-caught shrimp amounts to approximately 350 thousand tons per year, of which about 100 thousand tons represent non-food by-products. Considering the yield of shrimp heparinoids is about 320mg/kg of shrimp heads, containing 100-200UI/ mg of heparin-like anticoagulant activity, there is a large amount of resources still not being exploited.

Heparin production from porcine and bovine organs has the potential to carry impurities including viruses, endotoxins, prions and other agents, in addition to contaminants such as solvents and metals introduced during pharmaceutical-grade preparation. Heparin-like glycosaminoglycans from shrimp are noted to have lower but significant anticoagulant effects than mammalian heparin, but with negligible hemorrhagic activity [3]. With antithrombotic properties similar to heparin and inhibitory effects against viruses [4], possibly by binding to virus surface proteins [5], these molecules may represent potential treatments against severe pathogens like SARS-CoV-2.

1. Tang N, Huan Bai, Xing Chen, Jiale Gong, Dengju Li, et al. (2020) Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost 18(5): 1094-1099.
2. Cahú TB, Suzan D Santos, Aline Mendes, Carolina R Córdula, Suely F Chavante et al. (2012) Recovery of protein, chitin, carotenoids and glycosaminoglycans from Pacific white shrimp (Litopenaeus vannamei) processing waste. Process Biochem 47(4): 570-577.
3. Brito AS, Rômulo S Cavalcante, Lais CGF Palhares, Ashley J Hughes, Giulianna PV Andrade, et al. (2014) A non-hemorrhagic hybrid heparin/heparan sulfate with anticoagulant potential. Carbohydr Polym 99: 372-378.
4. Chen J, Shuhei Yamada, Yoshiki Hama, Ajaya Kumar Shetty, Takanari Kobayashi, et al. (2011) Unique heparan sulfate from shrimp heads exhibits a strong inhibitory effect on infections by dengue virus and Japanese encephalitis virus. Biochem Biophys Res Commun 412(1): 136-142.
5. Mycroft West CJ, Dunhao Su, Stefano Elli, Scott Guimond, Gavin Miller, et al. (2020) The 2019 coronavirus (SARS-CoV-2) surface protein (Spike) S1 receptor binding domain undergoes conformational change upon heparin binding. bioRxiv 18: 48.