Target-Based Drug Discovery, ADMET Profiling and Bioactivity Studies of Antibiotics as Potential Inhibitors of SARS-CoV-2 Main Protease (Mpro)

Abdul-Hammed, Misbaudeen Adedotun Ibrahim Olaide Falade Victoria Adeola Adepoju Adewusi John Olasupo Sabitu Babatunde Akinboade Modinat Wuraola

A recent outbreak of a new strain of Coronavirus (SARS-CoV-2) has become a global health burden, which has resulted in deaths. No proven drug has been found to effectively cure this fast-spreading infection, hence the need to explore old drugs with the known profile in tackling this pandemic. Computer-aided drug design approach involving virtual screening was used to obtain the binding scores and inhibiting efficiencies of previously known antibiotics against SARS-CoV-2 main protease (M pro ). In silico pre-clinical studies which include Drug-likeness, Bioactivity, and ADMET profiling were done using Molinspiration online tool and ADMET SAR2 webserver respectively, and the results were compared with those of drugs currently involved in clinical trials in the ongoing pandemic. Although antibiotics have been speculated to be of no use in the treatment of viral infections, literature has emerged lately to reveal antiviral potential and immune-boosting ability of antibiotics. This study identified Tarivid and Ciprofloxacin with binding affinities of -8.3 and − 8.1 kcal/mol, respectively as significant inhibitors of SARS-CoV-2 (M pro ) with better pharmacokinetics, drug-likeness and oral bioavailabity, bioactivity properties, ADMET properties and inhibitory strength compared to Remdesivir (-7.6 kcal/mol) and Azithromycin (-6.3 kcal/mol). These observations will provide insight for further research (clinical trial) in the cure and management of COVID-19.