Anin silicoperception for newly isolated flavonoids from peach fruit as privileged avenue for a countermeasure outbreak of COVID-19

摘要

3 '-Hydroxy-4 '-methoxy-chroman-7-O-beta-d-glucopyranoside4was first isolated from a natural source, together with three known compounds, the ferulic acid heptyl ester1, naringenin2, and 4,2 ',4 '-trihydroxy-6 '-methoxychalcone-4 '-O-beta-d-glucopyranoside3, which were isolated from peach [Prunus persica(L.) Batsch] fruits. These compounds were subjected to different virtual screening strategies in order to examine their activity to combat the COVID-19 outbreak. The study design composed of some major aspects: (a) docking with main protease (M-pro), (b) docking with spike protein, (c) 3D shape similarity study (Rapid Overlay Chemical Similarity-ROCS) to the clinically used drugs in COVID-19 patients, and finally, (d) the rule of five and the estimated pre-ADMT properties of the separated flavonoids. Docking study withM(pro)of SARS-CoV-2 (PDB ID:;6LU7, and ;6Y2F) showed that compound3, its aglycone part, and compound4have a strong binding mode to a protease receptor with key amino acids, especially Gln:166AA, and having a similar docking pose to co-crystalized ligands. Docking with the spike protein of SARS-CoV-2 illustrated that compounds3and4have a good binding affinity to PDB ID:;6VSBthrough the formation of HBs with Asp:;467Aand Asn:;422A. According to ROCS analysis, compounds1,3, and4displayed high similarities to drugs that prevent SARS-Co2 entry to the lung cells or block the inflammatory storm causing lung injury. Compounds3and4are good candidates for drug development especially because they showed predicted activity against SARS-CoV-2 through different mechanisms either by preventing genome replication or by blocking inflammatory storm that trigger lung injury. These compounds were isolated from peach fruit, and the study supports data and continues with the recommendation of peach fruits in controlling and managing COVID-19 cases.