In Silico Evaluation of Different Flavonoids from Medicinal Plants for Their Potency against SARS-CoV-2

Abstract

The ongoing pandemic situation of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a global threat to both the world economy and public health. Therefore, there is an urgent need to discover effective vaccines or drugs to fight against this virus. The flavonoids and their medicinal plant sources have already exhibited various biological effects, including antiviral, anti-inflammatory, antioxidant, etc. This study was designed to evaluate different flavonoids from medicinal plants as potential inhibitors against the spike protein (Sp) and main protease (Mpro) of SARS-CoV-2 using various computational approaches such as molecular docking, molecular dynamics. The binding affinity and inhibitory effects of all studied flavonoids were discussed and compared with some antiviral drugs that are currently being used in COVID-19 treatment namely favipiravir, lopinavir, and hydroxychloroquine, respectively. Among all studies flavonoids and proposed antiviral drugs, luteolin and mundulinol exhibited the highest binding affinity toward Mpro and Sp. Drug-likeness and ADMET studies revealed that the chosen flavonoids are safe and non-toxic. One hundred ns-MD simulations were implemented for luteolin-Mpro, mundulinol-Mpro, luteolin-Sp, and mundulinol-Sp complexes and the results revealed strong stability of these flavonoid-protein complexes. Furthermore, MM/PBSA confirms the stability of luteolin and mundulinol interactions within the active sites of this protein. In conclusion, our findings reveal that the promising activity of luteolin and mundulinol as inhibitors against COVID-19 via inhibiting the spike protein and major protease of SARS CoV-2, and we urge further research to achieve the clinical significance of our proposed molecular-based efficacy.

Molecular Docking and Dynamics Simulation of Several Flavonoids Predict Cyanidin as an Effective Drug Candidate against SARS-CoV-2 Spike Protein

“…Based on molecular docking and ADMET analysis, flavonoids, such as cyanidin-3-(p-coumaroyl)-rutinoside-5-glucoside, delphinidin-3-O-beta-D-glucoside 5-O-(6-coumaroyl-beta-D-glucoside), albireo delphine, apigenin 7-(6”-malonylglucoside), and (-) maackiain-3-O-glucosyl-6”-O-malonate were demonstrated as potent inhibitors against the spike protein, 3CLpro, and RdRP of SARS-CoV-2 [ 18 ]. Furthermore, molecular docking and simulation studies on flavonoid-protein complexes, including luteolin-spike protein and mundulinol-spike protein, have been found to demonstrate strong interactions compared to recently used FDA-approved drugs such as favipiravir, hydroxychloroquine, and lopinavir [ 19 ]. Flavonoids, such as dorsilurin E, euchrenone a11, and sanggenol O, were found to inhibit SARS-CoV-2 main protease (M pro ) [ 20 ].…”

Chemical and Pharmacological Profiling of Wrightia coccinea (Roxb. Ex Hornem.) Sims Focusing Antioxidant, Cytotoxic, Antidiarrheal, Hypoglycemic, and Analgesic Properties

“…Molecular docking analysis was performed to interpret the interactive profile of the four isolated compounds from W. coccinea with their target proteins. The widely used popular software packages, including PyRx, PyMoL 2.3, and BIOVA Discovery Studio version 4.5, were utilized during for the in silico study of the isolated compounds from W. coccinea according to the semiflexible procedures described in several studies [36][37][38][39][40][41].…”

Multifaceted roles of plant derived small molecule inhibitors on replication cycle of SARS-CoV-2

“…In-silico screening followed by molecular docking analyses suggested that the phytochemicals bisdemethoxycurcumin, scutellarin, desmethoxycurcumin, quercetin, myricetin, luteolin and mundulinol could potentially inhibit 3-CL pro as these compounds exhibit low binding energy [ 25 , 73 ]. Another study recommended certain compounds such as catechin, naringenin, kaempferol, glucosides, quercetin, and epicatechin-gallate as potential inhibitors of 3CLpro [ 43 ].…”