Design of SARS-CoV-2 Mpro, PLpro dual-target inhibitors based on deep reinforcement learning and virtual screening.

Background: Since December 2019, SARS-CoV-2 has continued to spread rapidly around the world. The effective drugs may provide a long-term strategy to combat this virus. The main protease (Mpro) and papain-like protease (PLpro) are two important targets for the inhibition of SARS-CoV-2 virus replication and proliferation. Materials & methods: In this study, deep reinforcement learning, covalent docking and molecular dynamics simulations were used to identify novel compounds that have the potential to inhibit both Mpro and PLpro. Results & conclusion: Three compounds were identified that can effectively occupy the Mpro protein cavity with the PLpro protein cavity and form high-frequency contacts with key amino acid residues (Mpro: His41, Cys145, Glu166; PLpro: Cys111). These three compounds can be further investigated as potential lead compounds for SARS-CoV-2 inhibitors.

The prevalence of sarcopenia and relationships between dietary intake and muscle mass in head and neck cancer patients undergoing radiotherapy: A longitudinal study.

PURPOSE: Our study aims to investigate dietary intake characteristics and their association with skeletal muscle mass in head and neck cancer patients treated with radiotherapy. METHODS: From March 2017 to August 2018, patients with head and neck cancer who received radiotherapy at our affiliated hospital were enrolled. Dietary intake was assessed through 24-hr dietary recall and skeletal muscle mass was evaluated by bioelectrical impedance analysis at three-time points. Appendicular skeletal muscle mass was adjusted for height squared defined sarcopenia and correlated with dietary intake by generalized estimating equations (GEE). RESULTS: This study sample comprised 287 patients [median age: 54 years; 187 (65.2%) men]. Median dietary intake at post-treatment was 14.95 kcal/kg/day energy and 0.63 g/kg/day protein. Skeletal muscle mass decreased significantly in all patients. The prevalence of sarcopenia increased from 24.4% before treatment to 46.7% at the end of treatment. Exploratory univariate GEE analysis revealed that radiotherapy time-point, male-gender, age ≥60 and decreased dietary energy intake significantly impacted on muscle loss represented by the appendicular skeletal muscle index. After controlling covariates, dietary energy intake was only positively associated with muscle loss in women (P = 0.013, 95% CI = 0.003-0.027) but not in men (P = 0.788, 95% CI = -0.007-0.009). CONCLUSION: While the loss in skeletal muscle is more prevalent in men receiving radiotherapy, the effects of dietary energy intake were only associated with women. A prospective randomized clinical trial is required to identify the appropriate amount of dietary energy supplement by gender in cancer patients treated with radiotherapy.