Computationally approached inhibition potential of Tinospora Cordifolia towards COVID-19 targets

Abstract

The recent emergence of novel coronavirus (SARS-CoV-2) has been a major threat to human society, as the challenge of finding a suitable drug or vaccine is not met till date. With increasing morbidity and mortality, the need for novel drug candidates is under great demand. The investigations are progressing towards COVID-19 therapeutics and among the various strategies employed, the use of repurposed drugs is competing along with novel drug inventions [1]. Based on the therapeutic significance, the chemical constituents from the extract of Tinospora Cordifolia belonging to various classes like alkaloids, lignans, steroids and terpenoids will be investigated as potential drug candidates for COVID-19. The inhibition potential of the proposed compounds against viral spike protein and human receptor ACE2 were evaluated by computational molecular modeling (Auto dock), along with their ADME/T properties. Prior to docking, the initial geometry of the compounds were optimized by Density functional theory (DFT) method employing B3LYP hybrid functional and 6-311++G (d,p) basis set. The results of molecular docking and ADME/T studies have revealed 6 constituents as potential drug candidates that can inhibit the binding of SARS-CoV-2 spike protein with the human receptor ACE2 protein. The narrowed down list of constituents from Tinospora Cordifolia have paved way for further tuning their ability to inhibit COVID-19 by modifying the chemical structures and by employing computational geometry optimization and docking methods.

In Silico Design and Investigation of Novel Thiazetidine Derivatives as Potent Inhibitors of PrpR in Mycobacterium tuberculosis

“…[25,26] Also by utilizing various computational methodologies, we have shown the possibility of several constituents of Tinospora Cordifolia as potent inhibitors for SARS-CoV-2 targets. [27] The Lipinski rule of five has furthermore been applied to identify therapeutic interactions which are reliable and effective. Moreover, we have recently reported a detailed overview on the synthetic approaches to potent heterocyclic inhibitors of tuberculosis.…”

“…Recently, we have demonstrated the activity of bi‐heterocyclic benzimidazole and thiazolidines derivatives as potential inhibitors to interact strongly with the active site amino acids of the Mycobacterium TB protein PrpR [25,26] . Also by utilizing various computational methodologies, we have shown the possibility of several constituents of Tinospora Cordifolia as potent inhibitors for SARS‐CoV‐2 targets [27] . The Lipinski rule of five has furthermore been applied to identify therapeutic interactions which are reliable and effective.…”