Strong Inhibitory Activity and Action Modes of Synthetic Maslinic Acid Derivative on Highly Pathogenic Coronaviruses: COVID-19 Drug Candidate
Raya Soltane, Amani Chrouda, Ahmed Mostafa, Ahmed A. Al‐Karmalawy, Karim Chouaïb, Abdelwaheb Dhahri, Rami Adel Pashameah, Ahlam Alasiri, Omnia Kutkat, Mahmoud Shehata, Hichem Ben Jannet, Jawhar Gharbi, Mohamed A. Ali
Abstract
In late December 2019, a novel coronavirus, namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), escaped the animal–human interface and emerged as an ongoing global pandemic with severe flu-like illness, commonly known as coronavirus disease 2019 (COVID-19). In this study, a molecular docking study was carried out for seventeen (17) structural analogues prepared from natural maslinic and oleanolic acids, screened against SARS-CoV-2 main protease. Furthermore, we experimentally validated the virtual data by measuring the half-maximal cytotoxic and inhibitory concentrations of each compound. Interestingly, the chlorinated isoxazole linked maslinic acid (compound 17) showed promising antiviral activity at micromolar non-toxic concentrations. Thoughtfully, we showed that compound 17 mainly impairs the viral replication of SARS-CoV-2. Furthermore, a very promising SAR study for the examined compounds was concluded, which could be used by medicinal chemists in the near future for the design and synthesis of potential anti-SARS-CoV-2 candidates. Our results could be very promising for performing further additional in vitro and in vivo studies on the tested compound (17) before further licensing for COVID-19 treatment.