Amentoflavone derivatives significantly act towards the main protease (3CLPRO/MPRO) of SARS-CoV-2: in silico admet profiling, molecular docking, molecular dynamics simulation, network pharmacology

Abstract

SARS-CoV-2 is the foremost culprit of the novel coronavirus disease 2019 (nCoV-19 and/or simply COVID-19) and poses a threat to the continued life of humans on the planet and create pandemic issue globally. The 3-chymotrypsin-like protease (M PRO or 3CL PRO ) is the crucial protease enzyme of SARS-CoV-2, which directly involves the processing and release of translated non-structural proteins (nsps), and therefore involves the development of virus pathogenesis along with outbreak the forecasting of COVID-19 symptoms. Moreover, SARS-CoV-2 infections can be inhibited by plant-derived chemicals like amentoflavone derivatives, which could be used to develop an anti-COVID-19 drug. Our research study is designed to conduct an in silico analysis on derivatives of amentoflavone (isoginkgetin, putraflavone, 4′′′′′′-methylamentoflavone, bilobetin, ginkgetin, sotetsuflavone, sequoiaflavone, heveaflavone, kayaflavone, and sciadopitysin) for targeting the non-structural protein of SARS-CoV-2, and subsequently further validate to confirm their antiviral ability. To conduct all the in silico experiments with the derivatives of amentoflavone against the M PRO protein, both computerized tools and online servers were applied; notably the software used is UCSF Chimera (version 1.14), PyRx, PyMoL, BIOVIA Discovery Studio tool (version 4.5), YASARA (dynamics simulator), and Cytoscape. Besides, as part of the online tools, the SwissDME and pKCSM were employed. The research study was proposed to implement molecular docking investigations utilizing compounds that were found to be effective against the viral primary protease (M PRO ). M PRO protein interacted strongly with 10 amentoflavone derivatives. Every time, amentoflavone compounds outperformed the FDA-approved antiviral medicine that is currently underused in COVID-19 in terms of binding affinity (− 8.9, − 9.4, − 9.7, − 9.1, − 9.3, − 9.0, − 9.7, − 9.3, − 8.8, and − 9.0 kcal/mol, respectively). The best-selected derivatives of amentoflavone also possessed potential results in 100 ns molecular dynamic simulation (MDS) validation. It is conceivable that based on our in silico research these selected amentoflavone derivatives more precisely 4′′′′′′-methylamentoflavone, ginkgetin, and sequoiaflavone have potential for serving as promising lead drugs against SARS-CoV-2 infection. In consequence, it is recommended that additional in vitro as well as in vivo research studies have to be conducted to support the conclusions of this current research study. Graphical abstract

Phytochemical Drug Discovery for COVID-19 Using High-resolution Computational Docking and Machine Learning Assisted Binder Prediction

“…97 For example, Zhu and Xie found that procyanidin b2 forms hydrogen bonding interactions with GLY 143 and GLU 166, 97 and Dey et al found that bilobetin forms hydrogen bonding interactions with GLU 166 and HIS 163. 100 We observed these same interactions among others.…”

Ganoderma microsporum immunomodulatory protein acts as a multifunctional broad-spectrum antiviral against SARS-CoV-2 by interfering virus binding to the host cells and spike-mediated cell fusion

“…Through high-throughput screening, drug repurposing, and in silico prediction, many studies have been conducted to identify potential candidates for inhibiting SARS-CoV-2 infection [11] , [12] , [13] , [14] , [15] , [16] . Despite of the potential effects on viral replication and translation, many of these candidates still lack in vitro and in vivo experiments to validate their functions, and the requirement of the long period of clinical trials for human usage [13] , [17] , [18] . Currently, the approved antiviral drugs focus on blocking viral replication by targeting viral protease or RNA-dependent-RNA polymerase (RdRp), such as Paxlovid and Molnupiravir [19] , [20] , [21] , [22] , [23] , [24] , [25] .…”

A comprehensive perspective of traditional Arabic or Islamic medicinal plants as an adjuvant therapy against COVID-19

“…Quercetin has also been discovered to have antiviral properties. Quercetin was found to be effective against human T-lymphotropic virus-induced budding in MT2 cells ( Coelho-dos-Reis et al, 2011 , Dey et al, 2022 ). Quercetin showed activity against dengue virus type-2 ( Mir et al, 2016 ).…”