Integration of LC-MS, NMR and molecular docking for profiling of bioactive diterpenes from Euphorbia mauritanica L. with in-vitro anti-SARS-CoV-2 activity.

Abstract

In spite of tremendous efforts exerted in the management of COVID-19, the absence of specific treatments and the prevalence of delayed and long-term complications termed post-COVID syndrome still urged all concerned researchers to develop a potent inhibitor of SARS-Cov-2. The hydromethanolic extracts of different organs of E. mauritanica were in-vitro screened for the anti-SARS-Cov-2 activity. Then, using an integrated strategy of LC-MS/MS, molecular network and NMR, the chemical profile of the active extract has been determined. Docking studies of the identified compounds in the active extract were carried out at different viral targets to in-silico identify the best target for these compounds. The leaves extract showed the best inhibitory effect with IC 50 8.231±0.04 μg/ml. Based on multiplex of LC-MS/MS, molecular network and NMR, the jatrophane diterpenes were tentatively annotated as the main metabolites of the bioactive leaves extract. In silico studies revealed the potentiality of the compounds in the most active extract to 3CLpro where the compound 20 showed the best binding affinity. Further attention should be paid to the isolation of various jatrophane diterpenes from Euphorbia and evaluating their effects toward SARS-Cov-2 and its molecular targets.