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BackgroundThe emergence and increased spread of microbial resistance is a major challenge to all health care systems worldwide. In primary care, acute respiratory tract infection (ARTI) is the health condition most strongly related to antibiotic overuse. ObjectiveThe RESIST program aims at optimizing antibiotic prescribing for ARTI in German primary care. By completing a problem-orientated online training course, physicians are motivated and empowered to utilize patient-centered doctor-patient communication strategies, including shared decision making, in the treatment of patients with ARTI. MethodsRESIST will be evaluated in the form of a nonrandomized controlled trial. Approximately 3000 physicians of 8 (out of 16) German federal states can participate in the program. Patient and physician data are retrieved from routine health care data. Physicians not participating in the program serve as controls, either among the 8 participating regional Associations of Statutory Health Insurance Physicians (control group 1) or among the remaining associations not participating in RESIST (control group 2). Antibiotic prescription rates before the intervention (T0: 2016, 1st and 2nd quarters of 2017) and after the intervention (T1: 3rd quarter of 2017 until 1st quarter of 2019) will be compared. The primary outcome measure is the overall antibiotic prescription rate for all patients insured with German statutory health insurance before and after provision of the online course. The secondary outcome is the antibiotic prescription rate for coded ARTI before and after the intervention. ResultsRESIST is publicly funded by the Innovations funds of the Federal Joint Committee in Germany and was approved in December 2016. Recruitment of physicians is now completed, and a total of 2460 physicians participated in the intervention. Data analysis started in February 2020. ConclusionsWith approximately 3000 physicians participating in the program, RESIST is among the largest real-world interventions aiming at reducing inadequate antibiotic prescribing for ARTI in primary care. Long-term follow up of up to 21 months will allow for investigating the sustainability of the intervention. Trial RegistrationISRCTN Registry ISRCTN13934505; http://www.isrctn.com/ISRCTN13934505 International Registered Report Identifier (IRRID)RR1-10.2196/18648

New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to arise and prolong the coronavirus disease 2019 (COVID-19) pandemic. Here, we used a cell-free expression workflow to rapidly screen and optimize constructs containing multiple computationally designed miniprotein inhibitors of SARS-CoV-2. We found the broadest efficacy was achieved with a homotrimeric version of the 75-residue angiotensin-converting enzyme 2 (ACE2) mimic AHB2 (TRI2-2) designed to geometrically match the trimeric spike architecture. Consistent with the design model, in the cryo-electron microscopy structure TRI2-2 forms a tripod at the apex of the spike protein that engaged all three receptor binding domains simultaneously. TRI2-2 neutralized Omicron (B.1.1.529), Delta (B.1.617.2), and all other variants tested with greater potency than the monoclonal antibodies used clinically for the treatment of COVID-19. TRI2-2 also conferred prophylactic and therapeutic protection against SARS-CoV-2 challenge when administered intranasally in mice. Designed miniprotein receptor mimics geometrically arrayed to match pathogen receptor binding sites could be a widely applicable antiviral therapeutic strategy with advantages over antibodies in greater resistance to viral escape and antigenic drift, and advantages over native receptor traps in lower chances of autoimmune responses.