Does the SARS-CoV-2 Spike Protein Receptor Binding Domain Interact Effectively with the DPP4 (CD26) Receptor? A Molecular Docking Study.

ACE2 has been established as the main receptor for SARS-CoV-2. Since other human coronaviruses are known to use co-receptors for viral cell entry, it has been suggested that DPP4 (CD26) could be a potential additional binding target or co-receptor, supported by early molecular docking simulation studies. However, recent biophysical studies have shown this interaction to be very weak. We have conducted detailed molecular docking simulations to predict the potential binding interactions between the receptor binding domain (RBD) of the spike protein of SARS-CoV-2 and DPP4 and compare them with the interactions observed in the experimentally determined structure of the complex of MERS-CoV with DPP4. Whilst the overall binding mode of the RBD of SARS-CoV-2 to DPP4 is predicted to be similar to that observed in the MERS-CoV-DPP4 complex, including a number of equivalent interactions, important differences in the amino acid sequences of SARS-CoV-2 and MERS-CoV result in substantially weakened interactions with DPP4. This is shown to arise from differences in the predicted proximity, nature and secondary structure at the binding interface on the RBD of SARS-CoV-2. These findings do not support DPP4 being a significant receptor for SARS-CoV-2.

Patient satisfaction with musculoskeletal physical therapy care: a systematic review.

BACKGROUND: Patient satisfaction is an important patient-centered health outcome. To date, no systematic review of the literature on patient satisfaction with musculoskeletal physical therapy care has been conducted. PURPOSE: The purpose of this study was to systematically and critically review the literature to determine the degree of patient satisfaction with musculoskeletal physical therapy care and factors associated with satisfaction. DATA SOURCES: The databases CINAHL, MEDLINE, and EBM Reviews were searched from inception to September 2009. STUDY SELECTION: Articles were included if the design was a clinical trial, observational study, survey, or qualitative study; patient satisfaction was evaluated; and the study related to the delivery of musculoskeletal physical therapy services conducted in an outpatient setting. The search located 3,790 citations. Fifteen studies met the inclusion criteria. DATA EXTRACTION: Two authors extracted patient satisfaction data and details of each study. DATA SYNTHESIS: A meta-analysis of patient satisfaction data from 7 studies was conducted. The pooled estimate of patient satisfaction was 4.44 (95% confidence interval=4.41-4.46) on a scale of 1 to 5, where 5 indicates high satisfaction and 1 indicates high dissatisfaction. Additional data were summarized in tables and critically appraised. LIMITATIONS: Nonrespondent bias from individual studies may affect the accuracy and representativeness of these data. CONCLUSION: Patients are highly satisfied with musculoskeletal physical therapy care delivered across outpatient settings in northern Europe, North America, the United Kingdom, and Ireland. The interpersonal attributes of the therapist and the process of care are key determinants of patient satisfaction. An unexpected finding was that treatment outcome was infrequently and inconsistently associated with patient satisfaction. Physical therapists can enhance the quality of patient-centered care by understanding and optimizing these determinants of patient satisfaction.