Title:Structural Bioinformatics Used to Predict the Protein Targets of Remdesivir and Flavones in SARS-CoV-2 Infection
VOLUME: 17
Author(s):Avram Speranta, Laura Manoliu, Catalina Sogor, Maria Mernea*, Corina Duda Seiman, Daniel Duda Seiman and Carmen Chifiriuc
Affiliation:University of Bucharest, Faculty of Biology, Department of Anatomy, Animal Physiology and Biophysics, 36-46 Bd. M. Kogalniceanu, 050107, Bucharest, University of Bucharest, Faculty of Biology, Department of Anatomy, Animal Physiology and Biophysics, 36-46 Bd. M. Kogalniceanu, 050107, Bucharest, University of Bucharest, Faculty of Biology, Department of Anatomy, Animal Physiology and Biophysics, 36-46 Bd. M. Kogalniceanu, 050107, Bucharest, University of Bucharest, Faculty of Biology, Department of Anatomy, Animal Physiology and Biophysics, 36-46 Bd. M. Kogalniceanu, 050107, Bucharest, West University of Timisoara, Faculty of Chemistry, Biology, Geography, Department of Chemistry and Biology, 16 Pestalozzi, 300115, Timisoara, Victor Babes University of Medicine and Pharmacy Timisoara, 2 Piata Eftimie Murgu, 300041, Timisoara, University of Bucharest, Faculty of Biology, Department of Botanics and Microbiology, 1‐3 Aleea Portocalelor Str, 60101 Bucharest
Keywords:SARS-CoV-2, flavones, remdesivir, molecular features, target prediction, structural biology.
Abstract:Background: During the current SARS-CoV-2 pandemic, the identification of effective
antiviral drugs is crucial. Unfortunately, no specific treatment or vaccine is available to date.
Objective: Here, we aimed to predict the interactions with 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).
Methods: Using 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.
Results: Our 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.
Conclusion: Our evaluation recommends remdesivir, pectolinarin, and ritonavir as promising anti-
SARS-CoV-2 agents.
