Balchaturbhadra Churna as a potential medicine for SARS-CoV2 infection in pediatric setting: An in silico study

Background: Balchaturbharda Churna (BC), is four ingredients (Aconitum heterophyllum Wall. Ex Royle, Pistacia integerrima stew. Ex brandis, Piper Longum Linn. and Cyperus rotundus linn.) Ayurvedic powder dosage form, which is commonly prescribed for treating fever, cough, diarrhea in pediatric setting.Objective: This present study evaluates the possible effect of phytochemicals from the ingredients of BC on SARS-CoV-2 main protease (MPro), RNA dependent RNA polymerase (RdRP) and spike-ACE2 (SA) complex through in silico evaluation. Materials and methods: X-ray crystal structure of MPro and SA complex with PDB IDs 6LU7 and 6LZG and the SWISS model of RdRP were used as the drug targets. An enhanced docking methodology has been implemented to perform the molecular docking of these phytochemicals against the above-mentioned drug targets of SARS-CoV-2. DOCK 6 was used to perform docking of these phytochemicals. The ADMET and drug likeliness properties for these selected phytochemicals was performed using SWISS ADME. Results: The ensemble docking studies suggest that aconitine, lappaaconitine from Aconitum heterophyllum, 2’-hydroxyisorientin from Pistacia intergerrima and guineesine, pipercide and piperoic acid from Piper longum hold the potential to bind favorably with the SARS-CoV-2 drug targets. The drug likeliness and ADMET properties were calculated for these phytochemicals indicate that all the three phytochemicals from Piper longum were observed to have considerate drug-likeliness and ADMET properties. Aconitine has molecular weight slightly higher than 500 kDA and has more than 10 hydrogen bond acceptors. Conclusion: The in-silico study demonstrates that phytochmeicals from the ingredients BC viz., aconitine, lappaaconitine from Aconitum heterophyllum, 2’-hydroxyisorientin from Pistacia intergerrima and guineesine, pipercide and piperoic acid from Piper longum hold the potential to bind favourably with the SARS-CoV-2 drug targets. The study also provides evidence for drug likeliness and ADMET properties for these phytochemicals suggesting that BC can be further studied as potential drug of choice for treating SARS-CoV-2 infection in paediatric cases.