Amentoflavone, New Hope against SARS-CoV-2: An Outlook through its Scientific Records and an in silico Study

Abstract

Background:The plant-derived bioflavonoid amentoflavone has many important biological activities, among them remarkable antiviral effects, even against severe acute respiratory syndrome Coronavirus (SARS-CoV). It inhibits severe acute respiratory syndrome coronavirus (SARS-CoV) with an IC 50 value of 8.3 µM. TMPRSS-2 activity is now thought to be the only factor necessary for cell entry and viral pathogenesis). In comparison, 3CL PRO is needed for COVID-19 replication and maturation during its life cycle. Aim: This study aims to perform an in silico study on amentoflavone activity against structural and non-structural severe acute respiratory syndrome coronavirus (SARS-CoV)-2 3-chymotrypsin-like protease (3CL PRO ) and human transmembrane protease serine 2 (TMPRSS-2) proteins. Materials and Methods: Molecular docking studies were carried out using compounds against 3CL PRO and TMPRSS-2 proteins through the Swiss model, Uniport, PROCHECK, Swiss PDB viewer, PyMol, PyRx, and Desmond (Schrödinger package) computerized software. Results: Amentoflavone showed strong interactions -9.5 and -7.4 kcal/mol with 3CL PRO and TMPRSS2 proteins, respectively. In any case, it had higher binding affinities than currently approved antiviral drugs, which are underutilized in coronavirus disease . Conclusion: Amentoflavone may be one of the potential leads (drug candidate) to fight human coronavirus, including SARS-CoV-2. Further in vivo studies are needed to support the findings of this study.

Design of a multi-epitope vaccine against SARS-CoV-2: immunoinformatic and computational methods

“…For TLR2-vaccine complex was placed in the orthorhombic box (buffer of 10 Å SPC) of 4 666 776 Å 3 containing 109 394 SPC water molecules, 626 POPC molecules, and 20 Na+ ions, while TLR2/MDM2-vaccine complex was placed in the orthorhombic box (buffer of 10 Å SPC) of 8 543 937 Å 3 containing 218 682 SPC water molecules, 922 POPC molecules, and 16 Na+ ions via the aid of system builder tool from Desmond package. 61 After then the systems were allowed to relax and equilibrate via implementing the Multisim method. 62 The MD simulation calculations were run under the constant pressure of 1.01325 bar and a temperature of 300 K, thermostated and barostated according to the Martyna–Tobias–Klein barostat algorithm with a relaxation time of 2 ps with isotropic coupling style and Nosé–Hoover thermostat algorithm (with a relaxation time of 1 ps) over 50 ns with recording intervals of 1.2 ps for energy and 100 ps for recording interval.…”

Colloidal aggregation confounds cell-based Covid-19 antiviral screens

“…Drug library molecules met the following criteria: they were reported entry inhibitors against SARS-CoV-2 or SARS in cell-based assays and were either previously reported as colloidal aggregators or structurally resembled known aggregators (e.g., conjugated ring systems and clogP typically >3; several were included that did not meet these criteria, mostly as internal controls) (Table S1) [17][18][19][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56]. We also tested one compound, amentoflavone that only had computational support for its role as an entry inhibitor, but had several reports of its potential as a COIVD-19 antiviral [57][58][59][60][61]. Among the 41 druglibrary molecules screened, 17 met all of our criteria for colloidal aggregation.…”

Biflavonoids: Important Contributions to the Health Benefits of Ginkgo (Ginkgo biloba L.)

“…[ 37 , 67 , 81 ]. In recent years, during the coronavirus pandemic, amentoflavone has become a molecule of interest due to its antiviral effects against SARS-CoV-2 based on in vitro and in silico studies [ 82 , 83 ]. Amentoflavone in vitro has the potential to inhibit herpes simplex virus 1 (HSV-1) including Acyclovir (ACV) (antiviral drug) -resistant strains [ 84 ].…”