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.
Highlights
Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is a family of enveloped positive-sense RNA viruses that cause life-threatening respiratory infections and severe pneumonia in humans [1,2]
The results suggest that natural emodins may prove to be effective inhibitors of COVID-19 by binding to the catalytic dyad, HIS41 and CYS145, through non-covalent forces near the active site [50]
Emodin is a natural anthraquinone commonly found in plants
Summary
Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is a family of enveloped positive-sense RNA viruses that cause life-threatening respiratory infections and severe pneumonia in humans [1,2]. The development of effective antiviral drugs with a broad spectrum of activity has been hampered by viral diversity and the ability of SARS-CoV to mutate rapidly, even during an epidemic. It is very important to develop antiviral drugs that effectively and safely inhibit the spread of SARS-CoV, or at least significantly alleviate the symptoms of SARS-CoV infection. Several potential repurposed drugs against COVID-19 (SARS-CoV-2 virus) have been found, such as remdesivir, infliximab and imatinib. To curb the spread of infection, it is important to identify new drug-leads that are more broadly effective against CoV
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