RESUMEN
The Influenza A virus is a continuous threat to public health that causes yearly epidemics with the ever-present threat of the virus becoming the next pandemic. Due to increasing levels of resistance, several of our previously used antivirals have been rendered useless. There is a strong need for new antivirals that are less likely to be susceptible to mutations. One strategy to achieve this goal is structure-based drug development. By understanding the minute details of protein structure, we can develop antivirals that target the most conserved, crucial regions to yield the highest chances of long-lasting success. One promising IAV target is the virulence protein non-structural protein 1 (NS1). NS1 contributes to pathogenicity through interactions with numerous host proteins, and many of the resulting complexes have been shown to be crucial for virulence. In this review, we cover the NS1-host protein complexes that have been structurally characterized to date. By bringing these structures together in one place, we aim to highlight the strength of this field for drug discovery along with the gaps that remain to be filled.
Asunto(s)
Virus de la Influenza A , Gripe Humana , Humanos , Inmunidad Innata , Replicación Viral/genética , Interferones/metabolismo , Antivirales/farmacología , Antivirales/metabolismo , Proteínas no Estructurales Virales/metabolismo , Interacciones Huésped-Patógeno/genéticaRESUMEN
BACKGROUND: Individuals with cancer experience loss of function and disability due to disease and cancer-related treatments. Physical fitness and frailty influence treatment plans and may predict cancer outcomes. Outcome measures currently used may not provide sufficiently comprehensive assessment of physical performance. OBJECTIVE: The objectives of this study are to: (1) describe the development of a functional measure, the Bellarmine Norton Assessment Tool (BNAT), for individuals with cancer; and (2) assess the relationship between the BNAT and the Eastern Cooperative Oncology Group (ECOG) Performance Status, a commonly used classification system by oncologists. DESIGN: This was a prospective cohort correlation study. METHODS: The BNAT encompasses 1 self-reported physical activity question and 4 objective tests: 2-Minute Step Test, 30-Second Sit to Stand, Timed Arm Curl, and Timed Up and Go. The BNAT score and its components were compared with ECOG Performance Status scores assigned by oncologists and analyzed for correlation and agreement. RESULTS: A total of 103 male and female individuals (ages 33-87 years) with various cancer diagnoses participated. The mean (SD) ECOG Performance Status score was 0.95 (0.87), range 0 to 3, and the mean BNAT score was 14.9 (4.3), range 5 to 24. Spearman agreement association of BNAT and ECOG Performance Status scores revealed a significant moderate negative relationship (r = -0.568). LIMITATIONS: The BNAT was compared with the ECOG Performance Status, a commonly used but subjective measure. Additionally, a common data set was used for both deriving and evaluating the BNAT performance scale. CONCLUSIONS: There was a moderate negative linear relationship of BNAT to ECOG Performance Status scores across all participants. Utilization of the BNAT may reflect overall physical performance and provide comprehensive and meaningful detail to influence therapeutic decisions.