Coronavirus disease 2019

Researchers evaluated the efficacy of small molecule drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro.

Entospletinib was found to be the most promising SYK inhibitor against severe COVID-19. Duvelisib, a PI3K-Gamma/Delta inhibitor reduced IL-6 expression upon co-stimulation of anti-S and polyinosinic:polycytidylic acid immunological complexes, the small molecule enhanced IL-6 production in a dose-dependent manner in the polyinosinic:polycytidylic acid-only condition. Entospletinib and R406 reduced IL-6 expression by 75% to 95% against all VOCs. Entospletinib counterbalanced the increased thrombus formation and lowered thrombus volume to that of COVA1-18 mAb controls. The authors of the present study previously showed that anti-SARS-CoV-2 S (spike) protein immunoglobulin G (IgG) titers are majorly involved in severe SARS-CoV-2 infections as they trigger macrophage hyperactivation, disrupt endothelial integrity, and induce the formation of thrombi. Platelet adhesion was assessed underflow to von Willebrand factor (vWF)- and S-targeted IgG immunological complexes formed by COVA1-18, a recombinant mAb (monoclonal antibody) showing anti-S IgG titers with atypical glycosylation (78% and nine percent galactosylated and fucosylated, respectively.