Flu and VRS 2018-19 Season and vaccine effectiveness against the need for hospital flu treatment in Guadalajara province, Spain
MEDICINA CLINICA
Authors: Gonzalez, Olga Redondo; Olteanu, Filip Camil Olteanu; Calderon, Juan Jose Arechederra; Villasenor, Clara Maria Bravo; Aguilar, Isabel Miras; Arbaizar, Jorge Rodriguez
Abstract
Introduction: The objective was to estimate the effectiveness of inactivated trivalent vaccine (VE) in preventing hospital flu care (HFC) in Guadalajara, Castile-La Mancha (CLM), Spain, 2018-19 season. Material and methods: Retrospective cohort study (40/2018 to 13/2019 weeks). Sources: Microbiology programme; electronic medical history; population census (INE, 1/7/2018). Cases: Population requiring HFC (hospital emergencies and/or emergency observation unit and/or hospital admissions), confirmed by antigenic test and/or PCR. Preventive fractions [PFv(vaccinated) and PFp(population)] and Necessary number of patients to be vaccinated (NNV) were calculated. Results: 228 HFT occurred [cumulative incidence rate (IR) = 8.9/10(4); >= 65 years = 65%; vaccination coverage = 13% (>= 65 years = 58%); mortality = 9%); maximum incidence in the 6th week (IR = 1.7/10(4)) (in CLM, in 4th)]. Highest peak of RSV occurred in the 3rd (in CLM, in the 52th). PFv (14-65 years) was 96% (PFp = 58%) and in >= 65, 32% (PFp = 21%). NNV = 414. As in Spain, influenza virus A predominated, with A(H3N2) being 13% more prevalent (strain not included in the vaccine). Conclusions: The season was delayed by sustained VRS circulation. The VE was lower than the national one. It is be essential to promote future campaigns to improve vaccination coverage. (C) 2020 Elsevier Espana, S.L.U. All rights reserved.
Discovery of a Potent Dual Inhibitor of Wild-Type and Mutant Respiratory Syncytial Virus Fusion Proteins
ACS MEDICINAL CHEMISTRY LETTERS
Authors: Yamaguchi-Sasaki, Toru; Tokura, Seiken; Ogata, Yuya; Kawaguchi, Takanori; Sugaya, Yutaka; Takahashi, Ryo; Iwakiri, Kanako; Abe-Kumasaka, Tomoko; Yoshida, Ippei; Arikawa, Kaho; Sugiyama, Hiroyuki; Kanuma, Kosuke
Abstract
A novel series of macrocyclic pyrazolo[1,5-a]pyrimidine derivatives as respiratory syncytial virus (RSV) fusion glycoprotein (F protein) inhibitors were designed and synthesized based on docking studies of acyclic inhibitors. This effort resulted in the discovery of several macrocyclic compounds, such as 12b, 12f, and 12h, with low nanomolar to subnanomolar activities against the wild-type RSV F protein A2. In addition, 12h showed a single-digit nanomolar potency against the previously reported drug-resistant mutant D486N. Molecular modeling and computational analyses suggested that 12h binds to the D486N mutant while maintaining a rigid bioactive conformation via macrocyclization and that it interacts with a hydrophobic cavity of the mutant using a new interaction surface of 12h. This report describes the rational design of macrocyclic compounds with dual inhibitory activities against wild-type and mutant RSV F proteins.