In silico analysis of selected components of grapefruit seed extract against SARS-CoV-2 main protease

Abstract

At the end of December 2019, first identified cases of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) started emerging. Ever since the emergence of the first case of infection with SARS-CoV-2 or COVID-19, it became the hottest research topic of numerous studies, in which scientists are trying to understand the path of infection, transmission, replication and viral action, all in order of finding a potential cure or vaccine applying various fundamental principles and methodologies. Using in silico method via AutoDock Vina 1.1.2., we analysed the binding affinity of six selected compounds from grapefruit seed extract (GSE) (narirutin, naringin, naringenin, limonin, ascorbic acid and citric acid) to SARS-CoV-2 main protease Mpro (PDB ID: 6Y84), using acetoside, remdesivir and gallic acid as a positive controls of binding affinity. Results showed highest affinity (rmsd l.b. 0.000; rmsd u.b. 0.000) for narirutin (-10.5), then for naringin (-10.1), acetoside (-10.0), limonin (-9.9), remdesivir (-9.6), naringenin (-8.2), ascorbic acid (-6.7), citric acid (-6.4) and gallic acid (-6.4), all expressed in kcal/mol. Our findings suggest that selected compounds from grapefruit seed extract represent potential inhibitors of SARS-CoV-2 Mpro, but further research is needed as well as preclinical and clinical trials for final confirmation of inhibitory functionality of these compounds.

Naringenin as a Possible Candidate Against SARS-CoV-2 Infection and in the Pathogenesis of COVID-19

“…209 In silico analysis showed that several components of grapefruit seed extract, including naringenin, bind with Mpro with a binding affinity of −8.2 kcal/mol. 195…”

“…Thus, the occurrence of Mpro only within SARS-CoV-2 and not in the host cell has focused attention on this as a possible inhibition site for COVID-19 treatment. [190][191][192][193][194][195] In a molecular docking study, aimed at identifying compounds found in medicinal plants with the potential to be COVID-19 Mpro inhibitors, NAR exhibited a binding energy of −7.99 kcal/mol when docking with Mpro (PDB:6LU7), suggesting NAR as a potential COVID-19 Mpro inhibitor. NAR forms H-bonds with the 6LU7 amino acid His164, Glu166, Asp187, and Thr190.…”

“…194 Using an in silico method, via AutoDock Vina 1.1.2., for selected components of grapefruit seed extract (narirutin, naringin, naringenin, limonin, ascorbic acid and citric acid) against SARS-CoV-2 main protease (PDB ID: 6Y84), naringenin was identified as one of the components, having a binding affinity of −8.2 kcal/mol. 195 In a docking study involving Mpro (PDB:6lu7) and Mpro (PDB: 6y2f), NAR displayed HB interactions with Glu166, Gly143, and Leu141 and two HBs with Thr25, respectively. 196 In addition to HB interactions, the 4´-hydroxyl group of NAR occupied the amino acid clefts through hydrophobic-hydrophobic interactions.…”

“…A study by Go et al showed that GSE plus xylitol as a nasal spray solution, commercially available as Xlear nasal spray, can be used as a potential adjunct treatment of COVID-19 209. In silico analysis showed that several components of grapefruit seed extract, including naringenin, bind with Mpro with a binding affinity of −8.2 kcal/mol 195.…”