Multiple enzymes and signaling pathways (including MMP-1, MMP-12, SARS-CoV-2 main protease, and COX-2)

This entry represents a heterogeneous collection of therapeutic targets: Matrix Metalloproteinases (MMP-1 and MMP-12), the SARS-CoV-2 main protease (Mpro), and Cyclooxygenase-2 (COX-2). MMP-1 and MMP-12 are zinc-dependent endopeptidases that degrade collagen and elastin, respectively, playing vital roles in tissue remodeling, wound healing, and the progression of chronic obstructive pulmonary disease (COPD) [1]. The SARS-CoV-2 main protease is a critical cysteine protease required for the viral replication cycle, as it cleaves viral polyproteins into functional non-structural proteins [2]. COX-2 is an inducible enzyme that catalyzes the rate-limiting step in the conversion of arachidonic acid to pro-inflammatory prostaglandins, making it a primary target for treating pain and inflammatory conditions [3]. While these targets belong to distinct biological pathways, they are all focal points for drug development in infectious, inflammatory, and degenerative diseases. Drugs such as nirmatrelvir target the viral protease, while selective NSAIDs like celecoxib target COX-2. Despite their therapeutic potential, these targets are associated with specific challenges, including the cardiovascular risks of COX-2 inhibition and the musculoskeletal side effects observed in clinical trials of MMP inhibitors. [1] UniProt Consortium, P03956/P39900. [2] Jin, Z., et al. (2020) Nature. [3] Simmons, D. L., et al. (2004) Pharmacological Reviews.

Other names

Matrix metalloproteinase-1Matrix metalloproteinase-12SARS-CoV-2 Mpro3C-like protease3CLproCyclooxygenase-2Prostaglandin-endoperoxide synthase 2PTGS2

Inhibition of viral polyprotein cleavage by the SARS-CoV-2 main protease; inhibition of prostaglandin synthesis via COX-2 blockade; and inhibition of extracellular matrix degradation by matrix metalloproteinases.