Progress of SARS-CoV-2 Main protease peptide-like inhibitors.

The pneumonia outbreak caused by Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) infection poses a serious threat to people worldwide. Although vaccines have been developed, antiviral drugs are still needed to combat SARS-CoV-2 infection due to the high mutability of the virus. SARS-CoV-2 main protein (Mpro ) is a special cysteine protease that is a key enzyme for SARS-CoV-2 replication. It is encoded by peptides and is responsible for processing peptides into functional proteins, making it an important drug target. The paper reviews the structure and peptide-like inhibitors of SARS-CoV-2 Mpro , also the binding mode and structure-activity relationship between the inhibitors and Mpro are introduced in detail. It is hoped that this review can provide ideas and help for the development of anti-coronavirus drugs such as COVID-19, and help to develop broad-spectrum antiviral drug for the treatment of coronavirus diseases as soon as possible.

Discovery a series of novel inhibitors of human dihydroorotate dehydrogenase: Biological activity evaluation and molecular docking.

Human dihydroorotate dehydrogenase (hDHODH) is a key enzyme that catalyzes the de novo synthesis of pyrimidine. In recent years, various studies have shown that inhibiting this enzyme can treat autoimmune diseases such as rheumatoid arthritis (RA) and cancer. This study designed and synthesized a series of novel thiazolidone hDHODH inhibitors. Through biological activity evaluation, Compound 14 was found to have high inhibitory activity, with an IC50 value reaching nanomolar level. Preliminary structure-activity relationship studies found that the carboxyl group in R1 and the naphthalene in R2 are key factors in improving activity. Through molecular docking, the binding mode between inhibitors and proteins was elucidated. This study provides an important reference for further optimizing hDHODH inhibitors.