Chromone-embedded Peptidomimetics and Furopyrimidines as Highly Potent SARS-CoV-2 Infection Inhibitors: A Molecular Docking Study

Abstract Background: Coronavirus disease 2019 (COVID-19) is a respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Controlling the spread of viruses is one of the main concerns of pharmaceutical companies. Looking at the viral infection cycle can lead to the development of effective drugs. Since cell entry and replication of SARS-CoV-2 play a crucial role in the life cycle of CoV, this study investigated how derivatives of chromone compounds inhibit viral entry and prevent viral replication. Method: In this study, the inhibitory effect of chromone-embedded peptidomimetics and furopyrimidines on 7BZ5 (spike receptor binding domain) from Severe acute respiratory syndrome CoV 2, Homo sapiens, and 6LU7 (main protease domain) from Bat SARS-like CoV were investigated via molecular docking. The crystal structure of these proteins was taken from the Protein Data Bank (PDB). The ligand binding interaction option was used to determine the inhibition site. For structure preparation, unwanted molecules were removed, and the 3D structure was protonated and energetically minimized using Molecular Environment Operation (MOE) software. The chromone derivatives were first designed in three dimensions, and their energy was minimized using MOE 2019. Then, the online software SwissADME was used to calculate the molecular drug likeness. Lipinski and Benigni-Bossa's rule evaluated chromone derivatives, and toxicity was calculated using Toxtree v3.1.0 software. Then the compounds with pharmacological properties were selected for molecular docking. Interactions were assessed by molecular docking with MOE 2019, and the S score was calculated. Result: The pharmacokinetic tests showed that the chromone derivatives of the peptidomimetic family had acceptable pharmacokinetic activity in the human body. Some compounds exhibited pronounced medicinal properties, including Ch-p1, Ch-p2, Ch-p6, Ch-p7, Ch-p12, and Ch-p13. Molecular docking also showed that these compounds bound with high affinity to the main protease of SARS-CoV-2. Ch-p7 had the highest binding energy, with an S-score of -8.7370. This compound was bound to Gln189 via a benzene ring and Asn142 via three bonds. Therefore, it is likely that the inhibitory property of this compound is more effective than the other compounds in this study. Conclusions: For the virus to replicate in the host cell, SARS-CoV-2 must bind to the receptor via the receptor-binding domains of the S1 subunit and then be proteolytically processed by the main protease. In the present study, the inhibition of viral replication was investigated, and the results showed that chromone derivatives were effective. Compared to other studies on this subject, chromone derivatives from the peptidomimetic family had a high inhibitory effect.