Abstract
SARS-CoV-2 is the causative agent of the COVID-19 pandemic. The approval of vaccines and small-molecule antivirals is vital in combating the pandemic. The viral polymerase inhibitors remdesivir and molnupiravir and the viral main protease inhibitor nirmatrelvir/ritonavir have been approved by the U.S. FDA. However, the emergence of variants of concern/interest calls for additional antivirals with novel mechanisms of action. The SARS-CoV-2 papain-like protease (PL pro ) mediates the cleavage of viral polyprotein and modulates the host’s innate immune response upon viral infection, rendering it a promising antiviral drug target. This Perspective highlights major achievements in structure-based design and high-throughput screening of SARS-CoV-2 PL pro inhibitors since the beginning of the pandemic. Encouraging progress includes the design of non-covalent PL pro inhibitors with favorable pharmacokinetic properties and the first-in-class covalent PL pro inhibitors. In addition, we offer our opinion on the knowledge gaps that need to be filled to advance PL pro inhibitors to the clinic.
【초록키워드】 SARS-CoV-2, viral infection, Vaccine, pandemic, innate immune response, Antiviral, molnupiravir, knowledge, COVID-19 pandemic, variant, Ritonavir, Remdesivir, inhibitors, variants, Protease inhibitor, Papain-like protease, cleavage, structure-based design, inhibitor, mechanism, Nirmatrelvir, pharmacokinetic, causative agent, clinic, approval, class, polymerase, offer, polyprotein, Host, antiviral drug target, U.S. FDA, highlight, combating, include, addition, approved, modulate, Encouraging, 【제목키워드】 challenge, targeting, Progress, the SARS-CoV-2,