Molecular Docking and Dynamics Identify Potential Drugs to be Repurposed as SARS-CoV-2 Inhibitors.

The novel coronavirus disease 19 (COVID-19) has resulted in an estimated 20 million excess deaths and the recent resurgence of COVID-19 in China is predicted to result in up to 1 million deaths over the next few months. With vaccines being ineffective in the case of immunocompromised patients, it is important to continue our quest for safe, effective and affordable drugs that will be available to all countries. Drug repurposing is one of the strategies being explored in this context. Recently, out of the 7817 drugs approved worldwide, 214 candidates were systematically down-selected using a combination of 11 filters including FDA/TGA approval status, assay data against SARS-CoV-2, pharmacokinetic, pharmacodynamic and toxicity profiles. These down-selected drugs were subjected in this study to virtual screening against various SARS-CoV-2 targets followed by molecular dynamics studies of the best scoring ligands against each target. The chosen molecular targets were spike receptor binding domain, nucleocapsid protein RNA binding domain and key nonstructural proteins 3, 5 and 12–14. Four drugs approved for other indications — alendronate, cromolyn, natamycin and treprostinil — look sufficiently promising from our in-silico studies to warrant further in-vitro and in-vivo investigations as appropriate to ascertain their extent of antiviral activities. The pandemic's death toll of more than 6.8 million deaths demand action. With vaccines that are inadequate for the immunocompromised, urgent focus shifts to safe treatment regimen. A rigorous study narrowed 214 repurposed drug candidates, identified alendronate, cromolyn, natamycin and treprostinil through virtual screening which needs to be evaluated in-vitro against COVID-19. [ABSTRACT FROM AUTHOR]