Abstract
Inhibiting the main protease 3CLpro is the most common strategy in the search for antiviral drugs to fight the infection from SARS-CoV-2. We report that the natural compound eugenol is able to hamper in vitro the enzymatic activity of 3CLpro, the SARS-CoV-2 main protease, with an inhibition constant in the sub-micromolar range (Ki = 0.81 μM). Two phenylpropene analogs were also tested: the same effect was observed for estragole with a lower potency (Ki = 4.1 μM), whereas anethole was less active. The binding efficiency index of these compounds is remarkably favorable due also to their small molecular mass (MW < 165 Da). We envision that nanomolar inhibition of 3CLpro is widely accessible within the chemical space of simple natural compounds.
Highlights
The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is having a strong impact on the social and economic conditions worldwide, as well as on the scientific community
We μM), a high particular, we have identified astackle a low3CLpro micromolar inhibitor
A combination of experimental and computational techniques were used to characterA combination of experimental and computational techniques were used to characize the interaction of eugenol, estragole, and anethole with the main protease 3CLpro, with terize the interaction of eugenol, estragole, and anethole with the main protease 3CLpro, particular regard to their inhibitory properties
Summary
The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is having a strong impact on the social and economic conditions worldwide, as well as on the scientific community. Collaborative efforts have been started to tackle the emergency, with the aim of improving the detection of infections, tracing the occurrence of potentially contagious contacts, adjusting the pre-existing medical therapies, developing vaccines for prevention and monoclonal antibodies for early treatment, and identifying new drugs against this viral infection. Discovering specific antiviral compounds against SARS-CoV-2 is still demanding. Only the broad-spectrum drug Remdesivir has been approved [1], in spite of its relatively low activity. The coronavirus genome contains two overlapping open reading frames (ORF1a and ORF1b) encoding polyproteins pp1a and pp1ab.
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