Polypharmacology guided drug repositioning approach for SARS-CoV2

Drug repurposing has emerged as an important strategy and it has a great potential in identifying therapeutic applications for COVID-19. An extensive virtual screening of 4193 FDA approved drugs has been carried out against 24 proteins of SARS-CoV2 (NSP1-10 and NSP12-16, envelope, membrane, nucleoprotein, spike, ORF3a, ORF6, ORF7a, ORF8, and ORF9b). The drugs were classified into top 10 and bottom 10 drugs based on the docking scores followed by the distribution of their therapeutic indications. As a result, the top 10 drugs were found to have therapeutic indications for cancer, pain, neurological disorders, and viral and bacterial diseases. As drug resistance is one of the major challenges in antiviral drug discovery, polypharmacology and network pharmacology approaches were employed in the study to identify drugs interacting with multiple targets and drugs such as dihydroergotamine, ergotamine, bisdequalinium chloride, midostaurin, temoporfin, tirilazad, and venetoclax were identified among the multi-targeting drugs. Further, a pathway analysis of the genes related to the multi-targeting drugs was carried which provides insight into the mechanism of drugs and identifying targetable genes and biological pathways involved in SARS-CoV2.

Automated summary

Drug repurposing is an important strategy with great potential for identifying therapeutic applications for COVID-19. A virtual screening of 4193 FDA approved drugs against 24 proteins of SARS-CoV2 has been conducted, resulting in the identification of top 10 drugs with therapeutic indications for various diseases. To address drug resistance, polypharmacology and network pharmacology approaches were employed, leading to the identification of multi-targeting drugs. Pathway analysis of the genes related to these drugs provides insights into the mechanism of action and potential targetable genes and pathways involved in SARS-CoV2.