Discovery of orally active SARS-CoV-2 papain-like protease (PLpro) inhibitors (preprint)

Vaccines and first-generation antiviral therapeutics have provided important protection against coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there remains a need for additional therapeutic options that provide enhanced efficacy and protection against potential viral resistance. The SARS-CoV-2 papain-like protease (PLpro) is one of two essential cysteine proteases involved in viral replication. While inhibitors of the SARS-CoV-2 main protease (Mpro) have demonstrated clinical efficacy, known PLpro inhibitors have to date lacked the inhibitory potency and requisite pharmacokinetics to demonstrate that targeting PLpro translates to in vivo efficacy in a preclinical setting. Herein, we report the machine learning-driven discovery of potent, selective, and orally available SARS-CoV-2 PLpro inhibitors, with lead compound PF-07957472 (4) providing robust efficacy in a mouse-adapted model of COVID-19 infection.

Developing a Behavior Change Framework for Pandemic Prevention and Control in Public Spaces in China

Preventive behavior, such as hand hygiene, facemask wearing, and social distancing, plays a vital role in containing the spread of viruses during pandemics. However, people in many parts of the world usually encounter difficulties adhering to this behavior due to various causes. Thus, this article aims to develop a research framework and propose design strategies to prompt individuals’ behavior change during pandemics. Initially, we integrated a literature review and a structured interview (n = 22) to ascertain the core factors impacting behavior change during pandemics. These factors were categorized into four aspects: perceptional factors (attitudes, subjective norms and perceived behavior control, risk perceptions);social factors (knowledge and information dissemination, governmental regulations);physical factors (tools and facilities and surveillance);and sociocultural factor (cultural contexts). Then, a theoretical framework with antecedents was developed to reveal behavior intention and formation process. After that, an empirical study was carried out to test the research framework through a questionnaire survey (n = 549). The research findings indicated that all derived factors could directly or indirectly affect individuals’ preventive behavior during pandemics. This article strives to provide valuable insights for different stakeholders when coping with pandemic situations.