in silico Screening of Potential Spike Glycoprotein Inhibitors of SARS-CoV-2 with Drug Repurposing Strategy

Abstract

Abstract COVID-19 has globally spread and has become a new pandemic, but there is still no effective drugs or vaccines to treat or prevent this disease. SARS-Cov-2 invades human cells through its spike proteins interacting with human ACE2 receptors. One strategy to prevent the virus from entering cells is the interruption of the viral spike protein interacting with ACE2. In such an emergent situation, drug repurposing is a promising method for rapid drug development. Here, we selected around 15000 molecular candidates including FDA-approved drugs from DrugBank and natural compounds from TCMSP to perform virtual screening for potential molecules that can target viral spike protein based on its crystal structure. In this article, we present the top 20 molecules with high binding affinity with spike protein, of which, digitoxin, a cardiac glycoside in DrugBank and bisindigotin in TCMSP, extracted from indigo naturalis and polygoni tinctorii foliu , have the highest docking scores. In addition, we also found that raltegravir, an HIV integrase inhibitor, has a relatively high binding score. Those molecules with high binding capacity to spike glycoprotein might be used by other researchers for further anti-COVID-19 drug development.