Do novel drugs for diabetes help in COVID‐19? Another brick in the wall?

Docking-based virtual screening studies aiming at the covalent inhibition of SARS-CoV-2 MPro by targeting the cysteine 145

“…( Mantero et al, 2020 ) For ibrutinib, two studies shows that this compound seems to have a protective role against COVID-19, although they hypothesize that it may be due to the anti-inflammatory effect of the Bruton’s tyrosine kinase pathway inhibition. ( Thibaud et al, 2020 ; Treon et al, 2020 ) For saxagliptin, Alicja Krejner-Bienias and colleagues hypothesized that antidiabetic drugs, gliptins, could prevent the virus from binding to dipeptidyl peptidase IV (DPP IV)( Krejner-Bienias et al, 2020 ) Saxagliptin could then have a double effect on both M Pro and DPP IV. For fosfomycin, no relationship between this compound and COVID-19 can be found in the literature to date.…”

Revolutionizing Treatment Strategies for Autoimmune and Inflammatory Disorders: The Impact of Dipeptidyl-Peptidase 4 Inhibitors

“…Based on the factors mentioned, it has been proposed that DPP4 inhibitors could be beneficial for COVID-19 patients, potentially by preventing the entry of the virus. 137 , 138 Structural models of DPP4 and its inhibitors, as well as the viral spike proteins of MERS-CoV and SARS-CoV-2, indicate that the binding sites for DPP4 inhibitors do not overlap with those for viral spike proteins. 139 , 140 It is hypothesized that DPP4 inhibitors may modulate the endocytic cascade of SARS-CoV-2 by interacting with caveolin-1, a scaffold protein required for endosome formation.…”

DPP4 Inhibitors and COVID-19–Holy Grail or Another Dead End?

“…Apart from ADA and aforementioned soluble DPP4, the function of membrane-bound form of this molecule may also be modified by novel group of synthetic DPP4 inhibitors (DPP4i), also known as gliptins. Since gliptins are widely used as antidiabetic agents, their presumable involvement in the DPP4-related modulation of COVID-19 clinical course, at least in diabetic patients, was independently postulated by several authors in the beginning of April 2020 (Drucker 2020 ; Iacobellis 2020 ; Krejner-Bienias et al 2020 ; Solerte et al 2020a ).…”

“…Based on aforementioned considerations, it was suggested that DPP4i could be beneficial for patients with COVID-19, possibly by interfering with entry of the virus (Krejner-Bienias et al 2020 ; Solerte et al 2020a ). However, in silico simulations concerning the molecular interaction between structural model of DPP4 and its inhibitors, or viral spike proteins of MERS-CoV and SARS-CoV-2, have clearly shown that binding sites for gliptins do not overlap with those for viral S proteins (Fig.…”