An exhaustive computational bioassessment of plant‐derived terpenoids as potential SARS‐CoV‐2 inhibitors

Abstract SARS‐CoV‐2, the virus behind the COVID‐19 pandemic, has drastically disrupted human populations, unleashing several waves of outbreaks across the globe. A major concern about the outbreak is its emergence as highly adaptive and contagious viral strains increasing in severity. A promising approach to counter this threat involves using specialized, plant‐derived therapeutics. The perspective of sixteen plant‐derived terpenoid compounds as antiviral agents against SARS‐CoV‐2 was analyzed via a combination of ADMET profiling and molecular docking. ADMET profiling, conducted using various combinatorial tools, facilitated a systematic appraisal of the selected bioactive entities. Compounds collectively satisfied Lipinski's rule, confirming their drug‐like nature. Absorption rates were high, with human intestinal absorption exceeding 90%. Metabolism studies demonstrated that these derivatives do not inhibit key cytochrome P450 enzymes, diminishing the likelihood of drug‐drug interactions. Excretion rates were predicted within a range of −0.065 to −0.915 log mL/min/kg, while toxicity profiling manifested low acute toxicity with LD 50 values between 1.803 and 3.452 mol/kg, classifying them as virtually harmless. Molecular docking revealed strong binding interactions towards the viral target protein 6Y84 and binding energies ranging from −10.79 to −6.88 kcal/mol. Particularly, limonin (−10.79 kcal/mol), celastrol (−10.46 kcal/mol), ursolic acid (−9.55 kcal/mol), and betulin (−9.05 kcal/mol) exhibited the highest binding affinities, speculating their impact as potent inhibitors of viral replication. These results suggest that the molecules have strong antiviral potential and warrant further investigation in drug development efforts against SARS‐CoV‐2.