Virtual Screening of Repurposed Drugs as Potential Spike Protein Inhibitors of Different SARS-CoV-2 Variants: Molecular Docking Study

Abstract

Like most of the RNA viruses, SARS-CoV-2 continuously mutates. Although many mutations have an insignificant impact on the virus properties, mutations in the surface protein, especially those in the receptor-binding domain, may lead to immune or vaccine escape variants, or altered binding activities to both the cell receptor and the drugs targeting such a protein. The current study intended to assess the ability of different variants of interest (VOIs) and variants of concern (VOCs) of SARS-CoV-2 for their affinities of binding to different repurposed drugs. Seven FDA approved drugs, namely, camostat, nafamostat mesylate, fenofibrate, umifenovir, nelfinavir, cefoperazone and ceftazidime, were selected based on their reported in vitro and clinical activities against SARA-CoV-2. The S1 protein subunit from eleven different variants, including the latest highly contiguous omicron variant, were used as targets for the docking study. The docking results revealed that all tested drugs possess moderate to high binding energies to the receptor-binding domain (RBD) of the S1 protein for all different variants. Cefoperazone was found to possess the highest binding energy to the RBD of the S1 protein of all the eleven variants. Ceftazidime was the second-best drug in terms of binding affinity towards the S1 RBD of the investigated variants. On the other hand, fenofibrate showed the least binding affinity towards the RBD of the S1 protein of all eleven variants. The binding affinities of anti-spike drugs varied among different variants. Most of the interacting amino acid residues of the receptor fall within the RBD (438–506).

Exploring the volatile metabolites of three Chorisia species: Comparative headspace GC–MS, multivariate chemometrics, chemotaxonomic significance, and anti-SARS-CoV-2 potential

“…Correspondingly, no specific treatments with considerable efficacy and safety levels have been developed for SARS-CoV-2 infections as yet. Thus, a large body of research has been devoted to halt the replication of that new coronavirus, targeting some viral proteins such as proteases, helicases, and polymerases ( Abdelhafez et al, 2022 , Eweas et al, 2022 , Samy et al, 2021 , Samy et al, 2022 ). In this regard, a wide array of plant metabolites has been studied using molecular docking techniques to mine for chemical scaffolds as possible leads to anti-SARS-CoV-2 drugs ( Abdelhafez et al, 2022 , Abdelkarem et al, 2022 , Erdogan, 2021 , Abdelgawad et al, 2022 , Samy et al, 2021 , Samy et al, 2022 ).…”

Genetics, structure, transmission, epidemiology, immune response, and vaccine efficacies of the SARS‐CoV‐2 Delta variant: A comprehensive review

“…Amino acids present at 438–506, a part of RBD, are responsible for higher virus transmission, infection, and immune escape 22,23 . The most well‐studied mutations currently include D614G, L452R, T478K, and P681R, located in the RBD or near the S1/S2 cleavage site.…”

“…21 Amino acids present at 438-506, a part of RBD, are responsible for higher virus transmission, infection, and immune escape. 22,23 The most well-studied mutations currently include D614G, L452R, T478K, and P681R, located in the RBD or near the S1/S2 cleavage site. The D614G spike mutation significantly increases viral entry efficiency by a proposed mechanism that allows the Spike protein to adopt a more open conformation to bind ACE2.…”

In Silico Targeting of Fascin Protein for Cancer Therapy: Benchmarking, Virtual Screening and Molecular Dynamics Approaches

“…Recently, computer-aided drug discovery (CADD) approaches, especially structure-based virtual screening (SBVS), have been commonly applied to new drug discovery in various disciplines [ 29 , 30 , 31 , 32 ]. Molecular docking tools become beneficial in predicting the binding poses of novel bioactive compounds and ranking them according to their scoring functions.…”