The emergence of severe acute respiratory syndrome (SARS-CoV-2) in 2019 marked the third occurrence of a highly pathogenic coronavirus in the human population since 2003. As the death toll surpasses 5 million globally and economic losses continue, designing drugs that could curtail infection and disease progression is critical. In the US, three highly effective Food and Drug Administration (FDA)–authorized vaccines are currently available, and Remdesivir is approved for the treatment of hospitalized patients. However, moderate vaccination rates and the sustained evolution of new viral variants necessitate the ongoing search for new antivirals. Several viral proteins have been prioritized as SARS-CoV-2 antiviral drug targets, among them the papain-like protease (PLpro) and the main protease (Mpro). Inhibition of these proteases would target viral replication, viral maturation, and suppression of host innate immune responses. Knowledge of inhibitors and assays for viruses were quickly adopted for SARS-CoV-2 protease research. Potential candidates have been identified to show inhibitory effects against PLpro and Mpro, both in biochemical assays and viral replication in cells. These results encourage further optimizations to improve prophylactic and therapeutic efficacy. In this review, we examine the latest developments of potential small-molecule inhibitors and peptide inhibitors for PLpro and Mpro, and how structural biology greatly facilitates this process.
【저자키워드】 COVID-19, SARS-CoV-2, main protease, 3CLpro, protease inhibitors, MPro, Papain-like protease, PLPro, 【초록키워드】 Treatment, Evolution, Vaccine, coronavirus, antivirals, Infection, drug, protease, inhibition, Prophylactic, hospitalized patients, antiviral drug, Disease progression, cells, viral replication, Research, death, targets, inhibitor, viral variant, Critical, moderate, food, acute respiratory syndrome, Viral protein, maturation, SARS-CoV-2 protease, therapeutic efficacy, inhibitory effect, candidate, innate immune responses, vaccination rate, highly pathogenic, Host, effective, Peptide inhibitor, biochemical assay, IMPROVE, Occurrence, virus, approved, facilitate, adopted, sustained, Potential, curtail, 【제목키워드】 development, targeting,