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.

It has been hypothesized that a disturbance of central self-tolerance to islet β cells may play a role in the enteroviral pathogenesis of type 1 diabetes. Whether enteroviruses can induce an impaired expression of β-cell self-antigens in thymic epithelial cells has been investigated in a murine thymic epithelial (MTE) cell line. This cell line was permissive to the diabetogenic group B4 coxsackievirus (CV-B4) strain CV-B4 E2 and spontaneously expressed type 2 insulin-like growth factor (Igf2), the dominant self-antigen of the insulin family. In this model, a persistent replication of CV-B4 E2 was obtained, as attested to by the prolonged detection of intracellular positive- and negative-strand viral RNA by reverse transcription-PCR (RT-PCR) and capsid protein VP1 by immunofluorescent staining and by the release of infectious particles in culture supernatants. The chronic stage of the infection was characterized by a low proportion of VP1-positive cells (1 to 2%), whereas many cells harbored enteroviral RNA, as displayed by RT-PCR without extraction applied directly to a few cells. Igf2 mRNA and IGF-2 protein were dramatically decreased in CV-B4 E2-infected MTE cell cultures compared with mock-infected cultures, whereas housekeeping and interleukin-6 ( Il6 ) gene expression was maintained and Igf1 mRNA was decreased, but to a lower extent. Inoculation of CV-B3, CV-B4 JVB, or echovirus 1 resulted in a low level of IGF-2 in culture supernatants as well, whereas herpes simplex virus 1 stimulated the production of the protein. Thus, a persistent infection of a thymic epithelial cell line with enteroviruses like CV-B4 E2 can result in a disturbed production of IGF-2, a protein involved in central self-tolerance toward islet β cells.