జర్నల్ ఆఫ్ ఇన్ఫెక్షియస్ డిసీజెస్ అండ్ థెరపీ

నైరూప్య

Identification of Promising High-Affinity Inhibitors of SARS-CoV-2 Main Protease from African Natural Products Databases by Virtual Screening

Oudou Diabate, Cheickna Cisse, Mamadou Sangare, Opeyemi Soremekun, Segun Fatumo, Jeffrey G. Shaffer, Seydou Doumbia, Mamadou Wele

With the rapid spread of the novel Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), the causative agent of COVID-19 pandemic, poses a serious threat to global public health and still requires further investigations into potential therapeutic agents. The availability of SARS-CoV-2 genomic data and efforts to determine the structure of the viral proteins facilitated the identification of potent inhibitors using structure-based methods and bioinformatics tools.

Some drugs candidates have been proposed to treat COVID-19, but their effectiveness has not been approved. However, it is important to find new targeted drugs to overcome the problem of drug resistance. Several viral proteins such as proteases, polymerases or structural proteins have been considered as potential therapeutic targets. However, the viral target must be essential for host invasion and meet certain drug eligibility criteria.

In this work, we selected the validated pharmacological target main protease Mpro and we performed high throughput virtual screening of Natural Products from African Databases such as NANPDB, EANPDB, AfroDb, and SANCDB to identify the most promising inhibitors with the best pharmacological properties.

In total, 8741 Natural Products NPs were virtually screened against the main protease of SARS-CoV-2. Two hundred and five (205) compounds showed high-affinity scores (less than -10.0 Kcal/mol), among which fifty-eight (58) filtered through Lipinski’s rules. Those NPs showed better affinity than known inhibitors (i.e., ABBV-744, Onalespib, Daunorubicin, Alpha-ketoamide, Perampanel, Carprefen, Celecoxib, Alprazolam, Trovafloxacin, Sarafloxacin, Ethyl biscoumacetat). Detail of their interactions with the protein were illustrated and discussed with comparative inhibitors. Those promising compounds could be considered for further investigations toward the development of SARS-CoV-2 drug.