SARS-CoV spike (S) protein, a type I membrane-bound protein, is essential for the viral attachment to the host cell receptor angiotensin-converting enzyme 2 (ACE2). Emodin, an anthraquinone compound derived from genus Rheum and Polygonum, significantly blocked the S protein and ACE2 interaction in a dose-dependent manner. It also inhibited the infectivity of S protein-pseudotyped retrovirus to Vero E6 cells. These findings suggested that emodin may be considered as a potential lead therapeutic agent in the treatment of SARS [1].

Alterations in coagulation parameters are associated with a worse prognosis in patients with COVID-19-associated pneumonia [2]. Interestingly, rhein was able to protect myocardial H9c2 cells against hypoxia/reoxygenation-induced injury via the AKT/GSK3β/p38 pathway [3]. In addition, many anthraquinones inhibit platelet aggregation [4]. For example, chrysophanol-8-O-glucoside, an anthraquinone derivative in rhubarb, exerts anti-platelet and anti-coagulant activities by inhibiting platelet phosphatidylserine exposure and prolonging the activated partial thromboplastin time [5].

• Another study performed with obtusifolin and aurantioobtusin suggested that these molecules are strong thrombin inhibitors [6].

• The data described raise the possibility that rhein, as an anthraquinone, may exhibit similar anti-coagulant effects. Rhein is a potential multi-target therapeutic compound for COVID-19, through its antiviral, cardioprotective effects.

References

1. Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction. Antiviral Res. 2007 May; 74(2): 92–101. doi: 10.1016/j.antiviral.2006.04.014

2. Disseminated intravascular coagulation in patients with 2019-nCoV pneumonia. J Thromb Haemost 2020;18(4):786–7.

3. Rhein protects the myocardiac cells against hypoxia/ reoxygention-induced injury by suppressing GSK3β activity. Phytomedicine 2018;51:1–6.

4. Potential inhibitors of platelet aggregation from plant sources, V. Anthraquinones from seeds of Cassia obtusifolia and related compounds. J Nat Prod 1990;53(3):630–3.

5. Chrysophanol-8-O-glucoside, an anthraquinone derivative in rhubarb, has antiplatelet and anticoagulant activities. J Pharmacol Sci 2012;118(2):245–54.

6. Anthraquinones from Cassiae semen as thrombin inhibitors: in vitro and in silico studies. Phytochemistry 2019;165:112025.