An in silico analysis of Ibuprofen enantiomers in high concentrations of sodium chloride with SARS-CoV-2 main protease.

2020 will be remembered worldwide for the outbreak of Coronavirus disease (COVID-19), which quickly spread until it was declared as a global pandemic. The main protease (Mpro) of SARS-CoV-2, a key enzyme in coronavirus, represents an attractive pharmacological target for inhibition of SARS-CoV-2 replication. Here, we evaluated whether the anti-inflammatory drug Ibuprofen, may act as a potential SARS-CoV-2 Mpro inhibitor, using an in silico study. From molecular dynamics (MD) simulations, we also evaluated the influence of ionic strength on the affinity and stability of the Ibuprofen-Mpro complexes. The docking analysis shows that R(-)Ibuprofen and S(+)Ibuprofen isomers can interact with multiple key residues of the main protease, through hydrophobic interactions and hydrogen bonds, with favourable binding energies (-6.2 and -5.7 kcal/mol, respectively). MM-GBSA and MM-PBSA calculations confirm the affinity of these complexes, in terms of binding energies. It also demonstrates that the ionic strength modifies significantly their binding affinities. Different structural parameters calculated from the MD simulations (120 ns) reveal that these complexes are conformational stable in the different conditions analysed. In this context, the results suggest that the condition 2 (0.25 NaCl) bind more tightly the Ibuprofen to Mpro than the others conditions. From the frustration analysis, we could characterize two important regions (Cys44-Pro52 and Linker loop) of this protein involved in the interaction with Ibuprofen. In conclusion, our findings allow us to propose that racemic mixtures of the Ibuprofen enantiomers might be a potential treatment option against SARS-CoV-2 Mpro. However, further research is necessary to determinate their possible medicinal use.Communicated by Ramaswamy H. Sarma.

Protection of ovarian tissue from radiotherapy.

Advances researches in the diagnosis and treatment of childhood, adolescent and adult cancer have greatly increased the life expectancy of premenopausal women with cancer. However, one of the serious side effects of these treatments is the risk of damage to fertility. The ovaries are very sensitive to cytotoxic and radiotherapeutic treatment. The only established method of fertility preservation is embryo cryopreservation according to the Ethics Committee of the American Society for Reproductive Medicine (2005), but this option requires the patient to be of pubertal age, have a partner or use donor sperm, and be able to undergo a cycle of ovarian stimulation, which is not possible when the radiotherapy has to be initiated immediately or when stimulation is contraindicated according to the type of cancer. For patients who need immediate radiotherapy, cryopreservation of ovarian tissue is the only possible alternative. This manuscript reports the different techniques of cryopreservation and the results of transplantation of cryopreserved ovarian tissue. The current techniques allow cryopreservation of human ovarian fragments for a long time with good follicular survival rate after thawing. Numerous studies ultimately in this field have demonstrated to improve the survival rate of the oocytes and cryopreserved follicles. Moreover this manuscript includes a case of a 17-year-old girl who had to undergo pelvic irradiation for non-Hodgkin's lymphoma and the laparoscopic treatment to preserve the fertility (Fig. 2, Ref. 47).

Gastric cryptosporidiosis as a clue for the diagnosis of the acquired immunodeficiency syndrome.

Cryptosporidium parvum has been detected with increasing frequency in the gastrointestinal tract, but involvement of the stomach is rarely reported. Whenever found in the histologic examination of the gastrointestinal mucosa, it should raise the suspicion of an immunocompromised host. We report a case of Cryptosporidium-associated erosive gastritis in a 64-year-old woman, who was found later to have the acquired immunodeficiency syndrome. Gastroduodenoendoscopy and biopsy of the gastric mucosa played an invaluable role in the diagnosis of cryptosporidiosis and to disclose the underlying immunodeficiency state.