RESUMO
Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious infection that may break the healthcare system of several countries. Here, we aimed at presenting a critical view of ongoing drug repurposing efforts for COVID-19 as well as discussing opportunities for development of new treatments based on current knowledge of the mechanism of infection and potential targets within. Finally, we also discuss patent protection issues, cost effectiveness and scalability of synthetic routes for some of the most studied repurposing candidates since these are key aspects to meet global demand for COVID-19 treatment.
Assuntos
Infecções por Coronavirus/tratamento farmacológico , Descoberta de Drogas , Reposicionamento de Medicamentos , Pneumonia Viral/tratamento farmacológico , Betacoronavirus , COVID-19 , Humanos , Pandemias , SARS-CoV-2 , Tratamento Farmacológico da COVID-19RESUMO
Introduction: The timely identification biologically active chemicals, in disease relevant screening assays, is a major endeavor in drug discovery. The existence of frequent hitters (FHs) in non-related assays poses a formidable challenge in terms of whether to consider these molecules as chemical gold or promiscuous non-selective reactive trash (also known as PAINS - pan assay interference compounds).Areas covered: In this review, the authors bring together expertize in synthetic chemistry, cheminformatics and biochemistry, three key areas for dealing with FHs. They discuss synthetic methods facilitating preparation of chemically diverse molecular libraries, while favoring activity in the biological space. They also survey and discuss recent computational advances in the prediction of PAINS from chemical structures. Finally, they review experimental approaches for the validation of the biological activity of screening hits and discuss alternatives for exploiting promiscuity and chemical reactivity.Expert opinion: It's essential to develop more efficient computational methods to reliably recognize PAINS in distinct molecular environments. Accordingly, advances in synthetic chemistry hold the promise to provide a better quality of chemical matter for drug discovery. Medicinal chemists should be more open to screening for hits showing biologically complex mechanisms of action rather than discarding molecules that may prove valuable as innovative disease treatments.