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Quercetin and Luteolin Are Single-digit Micromolar Inhibitors of the SARS-CoV-2 RNA-dependent RNA Polymerase

Munafò et al., Research Square, doi:10.21203/ (Preprint) (In Vitro)
Munafò et al., Quercetin and Luteolin Are Single-digit Micromolar Inhibitors of the SARS-CoV-2 RNA-dependent RNA Polymerase, Research Square, doi:10.21203/ (Preprint) (In Vitro)
Dec 2021   Source   PDF  
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In Vitro and In Silico study showing quercetin and luteolin inhibiting SARS-CoV-2 RNA-dependent RNA polymerase (RdRp).
7 In Vitro studies support the efficacy of quercetin [Aguado, Bahun, Goc, Kandeil, Munafò, Singh, Xu].
Munafò et al., 28 Dec 2021, preprint, 6 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
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Quercetin and Luteolin Are Single-digit Micromolar Inhibitors of the SARS-CoV-2 RNA-dependent RNA Polymerase
Federico Munafò, Elisa Donati, Nicoletta Brindani, Giuliano Ottonello, Andrea Armirotti, Marco De Vivo
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a global health pandemic. Among the viral proteins, RNA-dependent RNA polymerase (RdRp) is responsible for viral genome replication and has emerged as one of the most promising targets for pharmacological intervention against SARS-CoV-2. To this end, we experimentally tested luteolin and quercetin for their ability to inhibit the RdRp enzyme. These two compounds are ancestors of avonoid natural compounds known for a variety of basal pharmacological activities. Luteolin and quercetin returned a single-digit IC 50 of 4.6 µM and 6.9 µM, respectively. Then, through dynamic docking simulations, we identi ed possible binding modes of these compounds to a recently published cryo-EM structure of RdRp. Collectively, these data indicate that these two compounds are a valid starting point for further optimization and development of a new class of RdRp inhibitors to treat SARS-CoV-2 and potentially other viral infections.
Supporting Information. Supplementary gures reporting the: i) chromatography analysis of luteolin and quercetin (pages S2−S3), ii) chemical structures of luteolin and quercetin in different protonation states (page S4), iii) docking scores (page S5), iv) MD analysis (pages S6-S9). Supplementary Files This is a list of supplementary les associated with this preprint. Click to download.
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