Chromone-embedded peptidomimetics and furopyrimidines as highly potent SARS-CoV-2 infection inhibitors: docking and MD simulation study.

Chromone-embedded peptidomimetics and furopyrimidines as highly potent SARS-CoV-2 infection inhibitors: docking and MD simulation study.

Publication date: Sep 21, 2023

COVID-19 is a respiratory illness caused by SARS-CoV-2. Pharmaceutical companies aim to control virus spread through effective drugs. This study investigates chromone compound derivatives’ ability to inhibit viral entry and prevent replication. This study investigated the inhibitory effect of chromone-embedded peptidomimetics and furopyrimidines on 7BZ5 from Severe Acute Respiratory Syndrome CoV-2, Homo sapiens, and 6LU7 from Bat SARS-like CoV using molecular docking. The crystal structure of these proteins was obtained from the Protein Data Bank, and the inhibition site was determined using ligand binding interaction options. The 3D structure was protonated and energetically minimised using MOE software. Chromone derivatives were designed in three dimensions, and their energy was minimised using MOE 2019. The molecular drug-likeness was calculated using SwissADME, Lipinski and Benigni-Bossa’s rule, and toxicity was calculated using Toxtree v3. 1.0 software. Compounds with pharmacological properties were selected for molecular docking, and interactions were assessed using MOE 2019. MD simulations of Mpro-ch-p complexes were performed to evaluate root mean square fluctuations (RMSF) and measure protein stability. The pharmacokinetic tests revealed that chromone derivatives of the peptidomimetic family have acceptable pharmacokinetic activity in the human body. Some compounds, such as Ch-p1, Ch-p2, Ch-p6, Ch-p7, Ch-p12, and Ch-p13, have pronounced medicinal properties. Molecular docking revealed high affinity for binding to SARS-CoV-2 protease. Ch-p7 had the highest binding energy, likely due to its inhibitory property. A 10 ns molecular dynamics study confirmed the stability of the protein-ligand complex, resulting in minimal fluctuations in the system’s backbone. The MM-GBSA analysis revealed free energies of binding of -‚ÄČ19. 54 kcal/mol. The study investigated the inhibition of viral replication using chromone derivatives, finding high inhibitory effects in the peptidomimetic family compared to other studies.

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Concepts Keywords
54kcal Chromone derivatives
Bat Infection inhibitors
Pharmaceutical Main protease domain
Severe Molecular docking
Swissadme SARS-CoV-2


Type Source Name
disease MESH SARS-CoV-2 infection
pathway REACTOME SARS-CoV-2 Infection
disease VO effective
disease IDO replication
disease MESH Severe Acute Respiratory Syndrome
disease IDO homo sapiens
disease IDO site
drug DRUGBANK Coenzyme M
pathway KEGG Viral replication
disease MESH Infection
disease MESH pneumonia
drug DRUGBANK Angiotensin II
disease IDO host
disease VO Glycoprotein
disease MESH chronic diseases
disease MESH uncertainty
disease MESH cancer
disease MESH complications
drug DRUGBANK Water
drug DRUGBANK Flunarizine
drug DRUGBANK L-Asparagine
drug DRUGBANK Amino acids
disease VO protocol
drug DRUGBANK Tretamine
drug DRUGBANK L-Valine
disease IDO assay
disease IDO organism
disease MESH death
disease MESH lung injury
disease VO time
disease VO vaccine
disease VO effectiveness
drug DRUGBANK Albendazole
disease VO gene
drug DRUGBANK (S)-Des-Me-Ampa
drug DRUGBANK Guanosine
drug DRUGBANK Troleandomycin
drug DRUGBANK Ledipasvir
drug DRUGBANK D-Alanine
drug DRUGBANK Butoconazole
drug DRUGBANK Gold

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