Plant‐derived chemicals as potential inhibitors of SARS‐CoV‐2 main protease (6LU7), a virtual screening study

Sisakht, Mohsen; Mahmoodzadeh, Amir; Darabian, Maryam

SARS‐CoV‐2 has caused millions of infections and more than 700,000 deaths. Taking the urgent need to find new therapeutics for coronavirus disease 2019 (COVID‐19), a dataset of plant‐based natural compounds was selected for the screening of antiviral activity. The viral 3‐chymotrypsin‐like cysteine protease (Mpro, 3CLpro) was selected as the target. Molecular docking was performed on 2,845 phytochemicals to estimate the spatial affinity for the active sites of the enzyme. The ADMET screening was used for the pharmacological and physicochemical properties of the hit compounds. Nelfinavir and Lopinavir were used as control for binding energy comparison. The top 10 hits, based on the binding energy (Kcal/mol), were Ginkgolide M (−11.2), Mezerein (−11), Tubocurarine (−10.9), Gnidicin (−10.4), Glycobismine A (−10.4), Sciadopitysin Z‐10.2), Gnididin (−9.2), Glycobismine A (−10.4), Sciadopitysin (−10.2), Gnididin (−9.20, Emetine (−8.7), Vitexin (−8.3), Calophyllolide (−8.3), and 6‐(3,3‐Dimethylallyl)galangin (−7.9). The binding energy for nelfinavir and lopinavir were − 9.1 and − 8.4, respectively. Interestingly, some of these natural products were previously shown to possess antiviral properties against various viruses, such as HIV, Zika, and Ebola viruses. Herein, we suggest several phytochemicals as the inhibitors of the main protease of SARS‐CoV‐2 that could be used in the fight against COVID‐19.