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Updated: Sep 27, 2025
Use of Viral Entry Assays and Molecular Docking Analysis for the Identification of Antiviral Candidates against Coxsackievirus A16
Published on: July 15, 2019
Blocking key mutated hotspot residues in the RBD of the omicron variant (B.1.1.529) with medicinal compounds to
Abbas Khan1, AsfandYar Waheed Randhawa2, Ali Raza Balouch2
1Department of Bioinformatics and Biological Statistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University Shanghai 200240 P.R. China dqwei@sjtu.edu.cn.
Abstract:
A new variant of SARS-CoV-2 known as the omicron variant (B.1.1.529) reported in South Africa with 30 mutations in the whole spike protein, among which 15 mutations are in the receptor-binding domain, is continuously spreading exponentially around the world. The omicron variant is reported to be highly contagious with antibody-escaping activity. The emergence of antibody-escaping variants is alarming, and thus the quick discovery of small molecule inhibitors is needed. Hence, the current study uses computational drug screening and molecular dynamics simulation approaches (replicated) to identify novel drugs that can inhibit the binding of the receptor-binding domain (RBD) with hACE2. Screening of the North African, East African and North-East African medicinal compound databases by employing a multi-step screening approach revealed four compounds, namely (-)-pipoxide (C1), 2-(p-hydroxybenzyl) benzofuran-6-ol (C2), 1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol (C3), and Rhein (C4), with excellent anti-viral properties against the RBD of the omicron variant. Investigation of the dynamics demonstrates stable behavior, good residue flexibility profiles, and structural compactness. Validation of the top hits using computational bioactivity analysis, binding free energy calculations and dissociation constant (K D) analysis also indicated the anti-viral properties of these compounds. In conclusion, this study will help in the design and discovery of novel drug therapeutics, which may be used against the emerging omicron variant of SARS-CoV-2.
Insights
Researchers identified four novel compounds with potential antiviral properties against the SARS-CoV-2 omicron variant. These compounds show promise for inhibiting the virus
Area of Science:
- Virology
- Computational Chemistry
- Drug Discovery
Background:
- The SARS-CoV-2 omicron variant (B.1.1.529) exhibits rapid global spread and antibody-evading properties due to numerous spike protein mutations.
- The emergence of highly contagious and immune-resistant variants necessitates the rapid identification of novel antiviral therapeutics.
Purpose of the Study:
- To computationally screen medicinal compound databases for novel inhibitors targeting the omicron variant's receptor-binding domain (RBD).
- To identify small molecules capable of inhibiting the interaction between the SARS-CoV-2 RBD and the human angiotensin-converting enzyme 2 (hACE2) receptor.
Main Methods:
- Multi-step computational drug screening of African medicinal compound databases.
- Molecular dynamics simulations to assess compound stability and interaction with the RBD.
- Computational bioactivity analysis, binding free energy calculations, and dissociation constant (KD) analysis for validation.
Main Results:
- Four compounds, (-)-pipoxide (C1), 2-(p-hydroxybenzyl) benzofuran-6-ol (C2), 1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol (C3), and Rhein (C4), demonstrated significant antiviral potential.
- Molecular dynamics simulations confirmed stable interactions and structural compactness of the identified compounds with the RBD.
- Validation analyses supported the antiviral efficacy of these compounds against the omicron variant.
Conclusions:
- The identified compounds exhibit promising antiviral properties against the SARS-CoV-2 omicron variant.
- This study provides a foundation for the rational design and discovery of new drug therapeutics to combat emerging SARS-CoV-2 variants.
