Abstract
Severe Acute Respiratory Syndrome Corona Virus 2 has altered life on a global scale. A concerted effort from research labs around the world resulted in the identification of potential pharmaceutical treatments for CoVID-19 using existing drugs, as well as the discovery of multiple vaccines. During an urgent crisis, rapidly identifying potential new treatments requires global and cross-discipline cooperation, together with an enhanced open-access research model to distribute new ideas and leads. Herein, we introduce an application of a deep neural network based drug screening method, validating it using a docking algorithm on approved drugs for drug repurposing efforts, and extending the screen to a large library of 750,000 compounds for de novo drug discovery effort. The results of large library screens are incorporated into an open-access web interface to allow researchers from diverse fields to target molecules of interest. Our combined approach allows for both the identification of existing drugs that may be able to be repurposed and de novo design of ACE2-regulatory compounds. Through these efforts we demonstrate the utility of a new machine learning algorithm for drug discovery, SSnet, that can function as a tool to triage large molecular libraries to identify classes of molecules with possible efficacy.
Highlights
Pathogens have wreaked havoc on human society for as long as human society has existed
S1 from the S protein of SARS-CoV-2 did not co-crystallized with ACE2 as observed by Yan et al [14], we posit that S1 cannot bind ACE2 in its open conformation [14]
(2) We compare SSnet scores to binding affinities computed by smina for a small library of Food and Drugs Administration (FDA) and World approved drugs for which docking method is feasible
Summary
Pathogens have wreaked havoc on human society for as long as human society has existed. Various forms of pathogenic microbes have marked pivotal points in human history among which the notable examples are plague, smallpox, tuberculosis, and cholera [1]. While most of these pathogens have been either eradicated or have a cure developed, as globalization increases, new emergent diseases remain an increasing global threat. Hantavirus, zika virus, human immunodeficiency virus, and coronaviruses are some of the viral families that have been identified and have continuously posed a threat in the past decades [2,3]. It is imperative that we develop rapid methods to identify putative therapeutics to combat future rounds of new emergent diseases
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