Molecular docking suggests repurposing of brincidofovir as a potential drug targeting SARS-CoV-2 ACE2 receptor and main protease

Abstract

The current outbreak of the highly transmittable and life-threatening severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved rapidly and posed a global health emergency. Many clinical trials are now being conducted to test possible therapies. To assist this, virtual screening via molecular docking was performed on several FDA-approved drugs, previously used in epidemics, and the top ten compounds were selected. These ten well-characterized drugs, previously used to treat malaria and Ebola infections, were screened based on their interactions with the SARS-CoV-2 ACE2 receptor and 3C-like protease. Compared to the other nine medicines, brincidofovir, an ether lipid ester analog of cidofovir with potent antiviral activity, showed the highest docking scores and binding interactions. Therefore, brincidofovir is worth further investigations and clinical trials as a possible therapeutic agent for the COVID-19 disease caused by the novel SARS-CoV-2.

Identification of Potential SARS-CoV-2 Main Protease and Spike Protein Inhibitors from the Genus Aloe: An In Silico Study for Drug Development

“…The solubility of small molecules impacts their bioavailability and the need for frequent dosing, hence we investigated the ADME properties, inhibition of cytochrome P450 (CYP), modulation of P-glycoprotein (Pgp), solubility, plasma protein binding and permeability of the top scoring compounds in our analysis. The best scoring compounds for both SARS-CoV-2 M pro and spike glycoprotein were tested for obeying Lipinski’s rule of five parameters, which states that drugs having log P ranging from 0 to 5, have high possibility of oral absorption [ 42 ]. Data ( Table 2 ) showed that the compounds have log P values that ranged from −1.06 to 2.8 that does not exceed 5.0 indicating reasonable probability of their good absorption.…”

“…In this study, two SARS-CoV-2 proteins which facilitate viral–host interaction and replication were selected from the RCSB protein databank ( , accessed on 20 February 2021). The proteins are SARS-CoV-2 main protease (PDB ID: 6LU7, resolution = 2.16 Å) [ 54 ] and spike glycoprotein (PDB ID: 6M0J, resolution = 2.45 Å) [ 42 ]. The 3D protein structures were prepared using Molecular Operating Environment software (MOE 2014.0901) Ligx option.…”

Genome-Scale Metabolic Model of Infection with SARS-CoV-2 Mutants Confirms Guanylate Kinase as Robust Potential Antiviral Target

“…A virtual screening method identified cidofovir as a potentially effective therapeutic against SARS-CoV-2 [ 48 ]. A molecular docking study suggests the repurposing of brincidofovir against SARS-CoV-2 [ 49 ]. For favipiravir, several clinical trials are listed in the ClinicalTrials database hosted by the U.S. National Library of Medicine [ 50 ], running in several countries, including Italy (NCT04336904), Turkey (NCT04474457), and the United States (NCT04358549).…”

Genome-Scale Metabolic Model of Infection with SARS-CoV-2 Mutants Confirms Guanylate Kinase as Robust Potential Antiviral Target

“…A virtual screening method identified cidofovir as a potentially effective therapeutic against SARS-CoV-2 [48]. A molecular docking study suggests the repurposing of brincidofovir against SARS-CoV-2 [49]. For favipiravir, several clinical trials are listed in the Clinical-Trials database hosted by the U.S. National Library of Medicine [50], running in several countries, including Italy (NCT04336904), Turkey (NCT04474457), and the United States (NCT04358549).…”