TY - JOUR
T1 - Computational Study of SARS-CoV-2 RNA Dependent RNA Polymerase Allosteric Site Inhibition
AU - Faisal, Shah
AU - Badshah, Syed Lal
AU - Kubra, Bibi
AU - Sharaf, Mohamed
AU - Emwas, Abdul-Hamid M.
AU - Jaremko, Mariusz
AU - Abdalla, Mohnad
N1 - KAUST Repository Item: Exported on 2022-01-25
Acknowledgements: We appreciate King Abdullah University of Science and Technology, Saudi Arabia for their support.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
UR - http://hdl.handle.net/10754/674286
UR - https://www.mdpi.com/1420-3049/27/1/223
UR - http://www.scopus.com/inward/record.url?scp=85122017801&partnerID=8YFLogxK
U2 - 10.3390/molecules27010223
DO - 10.3390/molecules27010223
M3 - Article
C2 - 35011458
SN - 1420-3049
VL - 27
SP - 223
JO - Molecules
JF - Molecules
IS - 1
ER -
