Discovery of Potential Flavonoid Inhibitors Against COVID-19 3CL Proteinase Based on Virtual Screening Strategy

Abstract

The outbreak of 2019 novel coronavirus (COVID-19) has caused serious threat to public health. Discovery of new anti-COVID-19 drugs is urgently needed. Fortunately, the crystal structure of COVID-19 3CL proteinase was recently resolved. The proteinase has been identified as a promising target for drug discovery in this crisis. Here, a dataset including 2030 natural compounds was screened and refined based on the machine learning and molecular docking. The performance of six machine learning (ML) methods of predicting active coronavirus inhibitors had achieved satisfactory accuracy, especially, the AUC (Area Under ROC Curve) scores with fivefold cross-validation of Logistic Regression (LR) reached up to 0.976. Comprehensive ML prediction and molecular docking results accounted for the compound Rutin, which was approved by NMPA (National Medical Products Administration), exhibited the best AUC and the most promising binding affinity compared to other compounds. Therefore, Rutin might be a promising agent in anti-COVID-19 drugs development.

Flavonoids are promising safe therapy against COVID-19

“…Furthermore, a computational study indicated the potential importance of several flavonoids including kaempferol, quercetin, luteolin-7-glucoside, apigenin-7-glucoside, naringenin, catechin, and epigallocatechin as potential inhibitors to SARS-CoV-2 M pro (Khaerunnisa et al 2020 ). Additionally, rutin was suggested as a potential anti-SARS-CoV-2 M pro following a virtual screening of 2030 natural compounds (Xu et al 2020 ).

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Evolving scenario of big data and Artificial Intelligence (AI) in drug discovery

“…Numerous studies have been performed to identify potent lead molecules against the novel coronavirus using traditional medicine. Xu et al used ML and molecular modelling to identify the inhibitors against 3CL proteinase [ 149 ]. The deep learning approach has also assisted in the identification of potential drug targets for SARS-CoV-2 [ 150 ].…”

Drug Repurposing Strategy (DRS): Emerging Approach to Identify Potential Therapeutics for Treatment of Novel Coronavirus Infection

“…Based on the prediction of machine learning (ML) and molecular docking study, flavonoid like Rutin is found as potential inhibitor of COVID-19 3CL proteinase. From the result analysis, it was observed that the compound Rutin exhibit docking score of -9.16 kcal/mol and AUC: 0.990 ( Figure 9) (Xu et al, 2020). Enmozhi et al, 2020 has performed the evaluation of Andrographolide as a potential inhibitor of the main protease (Mpro) of SARS-COV-2 by using in-silico methods such as molecular docking.…”