Computational screening of repurposed drugs and natural products against SARS-Cov-2 main protease (Mpro) as potential COVID-19 therapies

Sakshi Piplani, Puneet Singh, Nikolai Petrovsky, David Winkler

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Received date: 11th September 2020

We urgently need to identify drugs to treat patients suffering from COVID-19 infection.  Drugs rarely act at single molecular targets. Off target effects are responsible for undesirable side effects, beneficial synergy between targets for specific illnesses, and have provided blockbuster drugs, e.g. Viagra for erectile dysfunction and Minoxidil for male pattern baldness. Existing drugs, those in clinical trials, and approved natural products constitute a rich resource of therapeutic agents that can be quickly repurposed, as they have already been assessed for safety in man.  A key question is how to rapidly and efficiently screen such compounds for activity against new pandemic pathogens such as COVID-19. Here we show how a fast and robust computational process can be used to screen large libraries of drugs and natural compounds to identify those that may inhibit the main protease of SARS-Cov-2. We show how the shortlist of candidates with strongest binding affinities is highly enriched in compounds independently identified as potential antivirals against COVID-19.  The top candidates also include a drugs and natural products not previously identified as having COVID-19 activity, thereby providing leads for experimental validation. This in silico screening pipeline will be valuable for repurposing existing drugs and discovering new drug candidates against other medically important pathogens relevant to future pandemics.

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This is an abstract of a preprint hosted on a preprint server, which is currently undergoing peer review at Scientific Reports. The findings have yet to be thoroughly evaluated, nor has a decision on ultimate publication been made. Therefore, the results reported should not be considered conclusive, and these findings should not be used to inform clinical practice, or public health policy, or be promoted as verified information.

Scientific Reports

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