Key result
Naringoside, Myricetin, and Aureusidin 4,6-diglucoside emerge as strong, stable inhibitors of the SARS-CoV-2 RdRp allosteric site.
Why the study?
New SARS-CoV-2 strains cause rapid disease progression and threaten vaccine efficacy, necessitating novel inhibitors targeting the viral RNA dependent RNA polymerase allosteric site.
Computational screening identifies Naringoside, Myricetin, and Aureusidin 4,6-diglucoside as potential allosteric inhibitors of SARS-CoV-2 RdRp for future drug design.
These RdRp allosteric hits require experimental validation; leaves open any therapeutic role in COVID-19.
The COVID-19 pandemic has caused millions of fatalities since 2019. Despite the availability of vaccines for this disease, new strains are causing rapid ailment and are a continuous threat to vaccine efficacy. Here, molecular docking and simulations identify strong inhibitors of the allosteric site of the SARS-CoV-2 virus RNA dependent RNA polymerase (RdRp). More than one hundred different flavonoids were docked with the SARS-CoV-2 RdRp allosteric site through computational screening. The three top hits were Naringoside, Myricetin and Aureusidin 4,6-diglucoside. Simulation analyses confirmed that they are in constant contact during the simulation time course and have strong association with the enzyme's allosteric site. Absorption, distribution, metabolism, excretion and toxicity (ADMET) data provided medicinal information of these top three hits. They had good human intestinal absorption (HIA) concentrations and were non-toxic. Due to high mutation rates in the active sites of the viral enzyme, these new allosteric site inhibitors offer opportunities to drug SARS-CoV-2 RdRp. These results provide new information for the design of novel allosteric inhibitors against SARS-CoV-2 RdRp.
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Faisal et al. (2021) studied SARS-CoV-2. Flavonoids (Naringoside, Myricetin, Aureusidin 4,6-diglucoside) was evaluated on Binding affinity energy (S-Score) and stability (RMSD). Computational screening identified Naringoside, Myricetin, and Aureusidin 4,6-diglucoside as strong inhibitors of the SARS-CoV-2 RNA dependent RNA polymerase allosteric site, demonstrating stable binding during 100 ns molecular dynamics simulations.
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