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P-glycoprotein (P-gp) is involved in the transport of xenobiotic compounds and responsible for the decrease of the drug accumulation in multi-drug-resistant cells. In this investigation we compare several docking algorithms in order to find the conditions that are able to discriminate between P-gp binders and nonbinders. We built a comprehensive dataset of binders and nonbinders based on a careful analysis of the experimental data available in the literature, trying to overcome the discrepancy noticeable in the experimental results. We found that Autodock Vina flexible docking is the best choice for the tested options. The results will be useful to filter virtual screening results in the rational design of new drugs that are not expected to be expelled by P-gp.

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.