Ricerc@Sapienza

We read with interest the paper by Giacobbe et al. estimating a cumulative risk of developing at least one bloodstream infection (BSI) episode (largely due to Gram‐positive pathogens) of almost 50% after 30 days at risk in severe COVID‐19 patients. (2) Similarly, Somers et al. reported an increased risk to develop bacterial superinfections, principally represented by Staphylococcus aureus ventilatory associated pneumonia (VAP), in critically ill patients infected with SARS‐CoV‐2 and treated with Tocilizumab.

The thiadiazole scaffold is an important core moiety in a variety of clinical drug candidates targeting a range of diseases. For example, the 2,4,5-substituted 1,3,4-thiadiazole scaffold is present in a lead compound and at least two clinical candidates targeting the human motor protein Eg5, against neoplastic diseases.

The antitumor agent 6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio)hexan-1-ol (1) is a potent inhibitor of GSTP1-1, a glutathione S-transferase capable of inhibiting apoptosis by binding to JNK1 and TRAF2. We recently demonstrated that, unlike its parent compound, the benzoyl ester of 1 (compound 3) exhibits negligible reactivity towards GSH, and has a different mode of interaction with GSTP1-1. Unfortunately, 3 is susceptible to rapid metabolic hydrolysis.

RATIONALE: Complex immune dysregulation in interferon (IFN) and T cell response has been observed in human immunodeficiency virus (HIV-1)-infected patients as well as in coronavirus disease-2019 (COVID-19) patients. However, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)/HIV-1 coinfection has been described in only few cases worldwide and no data are available on immunological outcomes in HIV-1-patients infected with SARS-CoV-2.