Abstract
While vaccines remain at the forefront of global healthcare responses, pioneering therapeutics against SARS-CoV-2 are expected to fill the gaps for waning immunity. Rapid development and approval of orally available direct-acting antivirals targeting crucial SARS-CoV-2 proteins marked the beginning of the era of small-molecule drugs for COVID-19. In that regard, the papain-like protease (PLpro) can be considered a major SARS-CoV-2 therapeutic target due to its dual biological role in suppressing host innate immune responses and in ensuring viral replication. Here, we summarize the challenges of targeting PLpro and innovative early-stage PLpro-specific small molecules. We propose that state-of-the-art computer-aided drug design (CADD) methodologies will play a critical role in the discovery of PLpro compounds as a novel class of COVID-19 drugs.
Keywords: COVID-19; SARS-CoV-2; artificial intelligence; computer-aided drug design; papain-like protease; small molecules.
【저자키워드】 COVID-19, SARS-CoV-2, artificial intelligence, computer-aided drug design, Papain-like protease, small molecules., 【초록키워드】 Vaccine, innate immune response, drugs, drug, viral replication, Rapid, Small molecules, methodology, PLPro, Critical, waning immunity, therapeutic target, Compound, approval, SARS-CoV-2 protein, global healthcare, while, Host, responses, direct-acting antiviral, expected, 【제목키워드】 targeting,