No abstract

Introduction:The COVID-19 pandemic resulted in disastrous human and economic costs, mainly due to the initial lack of specific treatments. Complementary to immunotherapies, drug repurposing is possibly the best option to arrive at COVID-19 treatments in the short term. Areas covered: Repurposing prospects undergoing clinical trials or with some level of evidence emerging from clinical studies are overviewed. The authors discuss some possible intellectual property and commercial barriers to drug repurposing, and strategies to facilitate equitable access to incoming therapeutic solutions, highlighting the importance of collaborative drug discovery models. Based on a critical analysis of the available literature about in silico screens against SARS-CoV-2 main protease, the authors illustrate how frequently overconfident conclusions are being drawn in COVID-19-related literature. Expert opinion: Most of the current clinical trials on potential COVID-19 treatments are, in fact, drug repurposing examples. In October 2020, the FDA approved a repurposed antiviral, remdesivir, as the first treatment for COVID-19. Considering the high expectations invested in approaching therapeutic solutions, the scientific community must be careful not to raise unrealistic expectations. Today more than ever, the conclusions drawn in scientific reports have to be fully supported by the level of evidence, avoiding any sort of unfounded speculation.

The scientific community is working against the clock to arrive at therapeutic interventions to treat patients with COVID-19. Among the strategies for drug discovery, virtual screening approaches have the capacity to search potential hits within millions of chemical structures in days, with the appropriate computing infrastructure. In this article, we first analyzed the published research targeting the inhibition of the main protease (Mpro), one of the most studied targets of SARS-CoV-2, by docking-based methods. An alarming finding was the lack of an adequate validation of the docking protocols (i.e., pose prediction and virtual screening accuracy) before applying them in virtual screening campaigns. The performance of the docking protocols was tested at some level in 57.7% of the 168 investigations analyzed. However, we found only three examples of a complete retrospective analysis of the scoring functions to quantify the virtual screening accuracy of the methods. Moreover, only two publications reported some experimental evaluation of the proposed hits until preparing this manuscript. All of these findings led us to carry out a retrospective performance validation of three different docking protocols, through the analysis of their pose prediction and screening accuracy. Surprisingly, we found that even though all tested docking protocols have a good pose prediction, their screening accuracy is quite limited as they fail to correctly rank a test set of compounds. These results highlight the importance of conducting an adequate validation of the docking protocols before carrying out virtual screening campaigns, and to experimentally confirm the predictions made by the models before drawing bold conclusions. Finally, successful structure-based drug discovery investigations published during the redaction of this manuscript allow us to propose the inclusion of target flexibility and consensus scoring as alternatives to improve the accuracy of the methods.

ResumenLa enfermedad de Peyronie es un trastorno de la túnica albugínea del pene caracterizada por la formación de placas fibrosas que conlleva a curvaturas patológicas del mismo.El presente artículo tiene como objetivo revisar los nuevos conceptos y los avances en los tratamientos, tanto quirúrgicos como no quirúrgicos, los orales o intralesionales, para manejar adecuadamente al paciente o para seguir un tratamiento que conlleve la mejoría de la sintomatología y de la calidad de vida de los hombres que padecen esta enfermedad.La enfermedad de Peyronie es un trastorno que no es tan infrecuente en la población masculina, que se acompaña de disfunción eréctil, una de las alteraciones que genera más consultas urológicas. AbstractPeyronie's disease, it is a disorder of the tunica albuginea of the penis, characterized by the formation of fibrotic plates that cause pathological curvatures of this organ. REVISIÓN DE TEMAPeyronie's disease is a disorder, not so infrequent in the masculine population which accompanies erectile dysfunction, one of the disorders that seen in urological services.