Structural bioinformatics used to predict the protein targets of remdesivir and flavones in SARS-CoV-2 infection.

Abstract

BACKGROUND\nDuring the current SARS-CoV-2 pandemic, the identification of effective antiviral drugs is crucial. Unfortunately, no specific treatment or vaccine is available to date.\n\n\nOBJECTIVE\nHere, we aimed to predict the interactions between SARS-CoV-2 proteins and protein targets from the human body for some flavone molecules (kaempferol, morin, pectolinarin, myricitrin, and herbacetin) in comparison to synthetic compounds (hydroxychloroquine, remdesivir, ribavirin, ritonavir, AMD-070, favipiravir).\n\n\nMETHODS\nUsing MOE software and advanced bioinformatics and cheminformatics portals, we conducted an extensive analysis based on various structural and functional features of compounds, such as their amphiphilic field, flexibility, and steric features. The structural similarity analysis of natural and synthetic compounds was performed using Tanimoto coefficients. The interactions of some compounds with SARS-CoV-2 3CLprotease or RNA-dependent RNA polymerase were described using 2D protein-ligand interaction diagrams based on known crystal structures. The potential targets of considered compounds were identified using the SwissTargetPrediction web tool.\n\n\nRESULTS\nOur results showed that remdesivir, pectolinarin, and ritonavir present a strong structural similarity which may be correlated to their similar biological activity. As common molecular targets of compounds in the human body, ritonavir, kaempferol, morin, and herbacetin can activate multidrug resistance-associated proteins, while remdesivir, ribavirin, and pectolinarin appear as ligands for adenosine receptors.\n\n\nCONCLUSION\nOur evaluation recommends remdesivir, pectolinarin, and ritonavir as promising anti-SARS-CoV-2 agents.