Theoretical and Computational Chemistry

Identification of SARS-CoV-2 Cell Entry Inhibitors by Drug Repurposing Using in Silico Structure-Based Virtual Screening Approach



The rapidly spreading, highly contagious and pathogenic SARS-coronavirus 2 (SARS-CoV-2) associated Coronavirus Disease 2019 (COVID-19) has been declared as a pandemic by the World Health Organization (WHO). The novel 2019 SARS-CoV-2 enters the host cell by binding of the viral surface spike glycoprotein (S-protein) to angiotensin converting enzyme 2 (ACE2). The virus specific molecular interaction with the host cell represents a promising therapeutic target for identifying SARS-CoV-2 antiviral drugs. The repurposing of drugs can provide a rapid and potential cure towards exponentially expending COVID-19. Thereto, high-throughput virtual screening approach was used to investigate FDA approved LOPAC library drugs against both the S-protein and ACE2 host cell receptor. Primary screening identified a few promising drugs for both the targets, which were further analyzed in details by their binding energy, binding modes through molecular docking, dynamics and simulations. Evidently, Eptifibatide acetate, TNP, GNF5, GR 127935 hydrochloride hydrate and RS504393 were found binding to virus binding motifs of ACE2 receptor. Additionally, KT185, KT203 GSK1838705A, BMS195614, and RS504393 were identified to bind at the receptor binding site on the viral S-protein. These identified drug molecules may effectively assist in controlling the rapid spread of SARS-COV-2 by not only potentially inhibiting the virus at entry step but also as anti-inflammatory agents which could impart relief in lung injuries. Timely identification and determination of an effective drug to combat and tranquilize the COVID-19 global crisis is the utmost need of hour. Further, prompt in vivo testing to validate the anti-SARS-COV-2 inhibition by these drugs could save lives is justified.


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Supplementary material

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