TMPRSS2, a novel host-directed drug target against SARS-CoV-2 was written by Keller, Christian;Boettcher-Friebertshaeuser, Eva;Lohoff, Michael. And the article was included in Signal Transduction and Targeted Therapy in 2022.Category: tetrahydrofurans The following contents are mentioned in the article:
In a recent study in Nature, Shapira et al. reported that the peptidomimetic compound N-0385 inhibited SARS-CoV-2 infection in vitro in remarkably low concentrations by blocking the host cell protease TMPRSS2, which mediates proteolytic cleavage of the SARS-CoV-2 major surface glycoprotein spike(S). Antigenic escape by, e.g., the Omicron variant (B.1.1.529) may jeopardize passive immunization by monoclonal antibodies, calling for complementary concepts in prophylaxis and therapy. So far, these have concentrated on agents that directly interfere with viral replication, e.g., by inhibition of the viral 3CL proprotease (paxlovid), by inhibition of the RNA-dependent RNA polymerase (remdesivir), or by introducing copying errors (molnupiravir). Viral infection not only requires binding of S to its receptor angiotensin-converting enzyme 2 (ACE2) but also cleavage of S at two distinct sites by host cell proteases: First, furin (and related pro-protein convertases) cleaves at a polybasic site, generating the S1 and S2 subunits, which remainnon-covalently linked (S1/S2 site, Fig.1a). Mechanistically, TMPRSS2 inhibition results in incompletely cleaved, fusion-incompetent SARS-CoV-2 viruses that are unable to infect new host cells (Fig.1a). The data presented by Shapira et al. suggest spike maturation by inhibiting TMPRSS2 as a potent drug target in COVID-19 when the inhibitor is given before or early in infection. As an advantage over virus-directed therapies, host-directed targets have a low potential for resistance: The TMPRSS2 cleavage site of the SARS-CoV-2 spike protein has remained very conserved over the pandemic (Fig.1b), suggesting that N-0385 should retain a high potency against future variants of concern. Another advantage to target TMPRSS2 is its activating function in other viral infections (e.g., other corona viruses, influenza virus), which expands the field of potential applications for TMPRSS2 inhibitors. Broad-spectrum serine protease inhibitors against COVID-19 that were recently evaluated in clin. trials are i.v. nafamostat, a synthetic inhibitor, and aerosolized aprotinin, a protease inhibitor from bovine lung. This study involved multiple reactions and reactants, such as ((2R,3S,4R,5R)-3,4-Dihydroxy-5-((Z)-4-(hydroxyimino)-2-oxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl isobutyrate (cas: 2492423-29-5Category: tetrahydrofurans).
((2R,3S,4R,5R)-3,4-Dihydroxy-5-((Z)-4-(hydroxyimino)-2-oxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl isobutyrate (cas: 2492423-29-5) belongs to tetrahydrofuran derivatives. THF (Tetrahydrofuran) is a stable compound with relatively low boiling point and excellent solvency. THF (Tetrahydrofuran) is also used as a starting material for the synthesis of poly(tetramethylene ether) glycol (PTMG), etc.Category: tetrahydrofurans
Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem