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Over the years, human adenovirus (HAdV) has progressively been recognized as a significant viral pathogen. Traditionally associated with self-limited respiratory, gastrointestinal, and conjunctival infections, mainly in immunocompromised patients, HAdV is currently considered to be a pathogen presenting significant morbidity and mortality in both immunosuppressed and otherwise healthy individuals. Currently available therapeutic options are limited because of their lack of effectivity and related side effects. In this context, there is an urgent need to develop effective anti-HAdV drugs with suitable therapeutic indexes. In this work, we identified new serinol-derived benzoic acid esters as novel scaffolds for the inhibition of HAdV infections. A set of 38 compounds were designed and synthesized, and their antiviral activity and cytotoxicity were evaluated. Four compounds (13, 14, 27, and 32) inhibited HAdV infection at low micromolar concentrations (2.82–5.35 μM). Their half maximal inhibitory concentration (IC50) values were lower compared to that of cidofovir, the current drug of choice. All compounds significantly reduced the HAdV DNA replication process, while they did not block any step of the viral entry. Our results showed that compounds 13, 14, and 32 seem to be targeting the expression of the E1A early gene. Moreover, all four derivatives demonstrated a significant inhibition of human cytomegalovirus (HCMV) DNA replication. This new scaffold may represent a potential tool useful for the development of effective anti-HAdV drugs., This work has been supported by Ministerio de Ciencia, Innovación y Universidades, Plan Estatal 2017-2020 Retos-Proyectos I+D+i (PID2019-104767RB-I00), Ministerio de Economı́a y Competitividad, Plan Estatal 2013-2016 Retos-Proyectos I + D + i (CTQ2016-78580-C2-2-R) and by Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economia, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), cofinanced by European Development Regional Fund “A way to achieve Europe”, the Instituto de Salud Carlos III, Proyectos de Investigación en Salud (PI17/01055; PI18/01191) and Proyectos de Desarrollo Tecnológico en Salud (DTS17/00130), the Spanish Adenovirus Network (AdenoNet, BIO2015/68990-REDT), and the program “Nicolás Monardes” (C-0059-2018), Servicio Andaluz de Salud, Junta de Andalucía. M.V.-H. also thanks Ministerio de Economı́a y Competitividad, Plan Estatal 2013-2016 Excelencia I+D+i (CTQ2016-78703-P).

Resumen Introducción: debido a la emergencia del coronavirus SARS-CoV-2 desde diciembre del 2019, se ha generado un gran volumen de producción científica, en algún caso incierta o controvertida especialmente en el manejo farmacológico de los pacientes con esta infección; por lo tanto, se considera relevante buscar alternativas metodológicas para realizar su síntesis rigurosa, sistemática y de calidad, pero con menor tiempo de ejecución y menor costo. Objetivo: presentar la evidencia disponible respecto al manejo farmacológico de personas con sospecha o diagnóstico de infección respiratoria por SARS-CoV-2 (COVID-19) utilizando el método de revisiones sistemáticas rápidas (RS-R) en medicamentos poten- cialmente eficaces para su manejo. Metodología: se realizó una búsqueda sistemática y estructurada en Medline, Embase, Scopus, Cochrane Library, Clinical trials y Google Scholar en inglés. Los estudios incluidos fueron guías de práctica clínica, consensos, revisiones sistemáticas, metaanálisis, ensayos clínicos y otros estudios primarios. La búsqueda y extracción de datos se realizó por múltiples revisores, pero ninguna fue pareada. Resultados: dieciseis preguntas de interés clínico fueron resueltas, relacionadas con el uso en COVID-19 de lopinavir/ ritonavir, nelfinavir, oseltamivir, remdesivir, ribavirina, teicoplanina, umifenovir, favipiravir, tocilizumab, ivermectina y plasma convaleciente; también se evaluó el uso de medicamentos de soporte e incluidos en el manejo como la dexametasona, así como el uso concomitante de medicamentos que generaron dudas como son los AINES, los IECA y los ARA II. Conclusiones: los resúmenes de evidencia se muestran dentro del escenario de la pandemia como una buena alternativa metodológica para ofrecer información de calidad a corto plazo para los tomadores de decisiones. Abstract Introduction: Due to the emergence of the SARS-CoV-2 coronavirus since December 2019, a large volume of scientific production has been generated, in some cases uncertain or controversial, especially in the pharmacological management of patients with this infection; therefore, it is considered a relevant search for methodological alternatives to carry out its rigorous, systematic and quality synthesis, but with less execution time and lower cost. Objective: To present the available evidence regarding the pharmacological management of people with suspected or diagnosed respiratory SARS-CoV-2 (COVID-19) using the method of rapid systematic reviews (RS-R) in potentially effective drugs for their management. Methodology: A systematic and structured search was conducted in Medline, Embase, Scopus, Cochrane Library, Clinical trials and Google Scholar in English. Studies included clinical practice guidelines, consensus, systematic reviews, meta-analyses, clinical trials, and other primary studies. Data search and extraction were performed by multiple reviewers, but none were paired. Results: Sixteen questions of clinical interest were resolved, related to the use in COVID-19 of lopinavir/ritonavir, nelfinavir, oseltamivir, remdesivir, ribavirin, teicoplanin, umifenovir, favipiravir, tocilizumab, ivermectin, convalescent plasma; the use of support management drugs such as dexamethasone were also evaluated, as well as the concomitant use of drugs that generated doubts, such as NSAIDs, ACEis, and ARA IIs. Conclusions: Summaries of evidence are within the pandemic scenario as a good methodological alternative to offer quality information in the short term for decision-makers.