Antiviral Activities of Halogenated Emodin Derivatives against Human Coronavirus NL63

Abstract

The current COVID-19 outbreak has highlighted the need for the development of new vaccines and drugs to combat Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). Recently, various drugs have been proposed as potentially effective against COVID-19, such as remdesivir, infliximab and imatinib. Natural plants have been used as an alternative source of drugs for thousands of years, and some of them are effective for the treatment of various viral diseases. Emodin (1,3,8-trihydroxy-6-methylanthracene-9,10-dione) is a biologically active anthraquinone with antiviral activity that is found in various plants. We studied the selectivity of electrophilic aromatic substitution reactions on an emodin core (halogenation, nitration and sulfonation), which resulted in a library of emodin derivatives. The main aim of this work was to carry out an initial evaluation of the potential to improve the activity of emodin against human coronavirus NL63 (HCoV-NL63) and also to generate a set of initial SAR guidelines. We have prepared emodin derivatives which displayed significant anti-HCoV-NL63 activity. We observed that halogenation of emodin can improve its antiviral activity. The most active compound in this study was the iodinated emodin analogue E_3I, whose anti-HCoV-NL63 activity was comparable to that of remdesivir. Evaluation of the emodin analogues also revealed some unwanted toxicity to Vero cells. Since new synthetic routes are now available that allow modification of the emodin structure, it is reasonable to expect that analogues with significantly improved anti-HCoV-NL63 activity and lowered toxicity may thus be generated.

Promising Role of Emodin as Therapeutics to Against Viral Infections

“…In order to improve the activity of emodin against human coronavirus NL63 (HCoV-NL63) and also to generate a set of initial SAR guidelines, Monika et al prepared emodin derivatives and found that halogenation of emodin can improve the antiviral activity of which. Moreover, the most active compound was the iodinated emodin analogue E_3I, the anti-HCoV-NL63 activity of which was comparable to that of remdesivir ( Horvat et al, 2021 ). Of course, studies on emodin against COVID-19 to date are all based on in vitro experiments and there is limited discussion of its mechanisms, so more researches are needed to demonstrate the important role of emodin could play in this plague.…”

Key insights into secondary metabolites from various Chaetomium species

“…Emodin ( 1 ) reportedly exhibits laxative, antibacterial and anti-inflammatory effects (Akkol et al 2021 ). Additionally, it might exhibit potential antiviral activity against SARS-CoV-2 (Horvat et al 2021 ), being one of the most active components of Lianhua Qingwen, a traditional antiviral Chinese medicine formulation (Runfeng et al 2020 ).

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Therapeutic Options for the SARS-CoV-2 Virus: Is There a Key in Herbal Medicine?

“…38,39 A very recent study by Horvat et al also demonstrated the antiviral activity of emodin derivatives against human CoVs NL63. 40 However, longstanding use of emodin may cause renal toxicity, hepatotoxicity, and reproductive toxicity. 31…”