Structure-Based Virtual Identification of Natural Inhibitors of SARS-CoV-2 and its Delta and Omicron Variant Proteins

Abstract

Aim: Structure-based identification of natural compounds against SARS-CoV-2, Delta and Omicron target proteins. Materials & methods: Several known antiviral natural compounds were subjected to molecular docking and MD simulation against SARS-CoV-2 Mpro, Helicase and Spike, including Delta and Omicron Spikes. Results: Of the docked ligands, 20 selected for each complex exhibited overall good binding affinities (-7.79 to -5.06 kcal/mol) with acceptable physiochemistry following Lipinski's rule. Finally, two best ligands from each complex upon simulation showed structural stability and compactness. Conclusion: Quercetin-3-acetyl-glucoside, Rutin, Kaempferol, Catechin, Orientin, Obetrioside and Neridienone A were identified as potential inhibitors of SARS-CoV-2 Mpro, Helicase and Spike, while Orientin and Obetrioside also showed good binding affinities with Omicron Spike. Catechin and Neridienone A formed stable complexes with Delta Spike.

Plain language summary

Mutant strains of SARS-CoV-2 called ‘variants of concern’ (VOCs) are linked to a good ability to infect, re-infect and spread among people. They are also linked to poor ability to fight the disease and reduced effectiveness of vaccines. Delta and Omicron are important VOCs because they are difficult to control and treat. Specific resistance to some drugs used to treat COVID-19 poses a further challenge. Therefore, discovering natural or plant-derived drugs with no known resistance would be valuable to the treatment of COVID-19. In this study, we screen and identify seven plant-derived compounds that may be useful to treating COVID-19 – we identify Quercetin-3-acetyl-glucoside, Rutin, Kaempferol, Catechin, Orientin, Obetrioside and Neridienone A as potential candidates. Orientin, Obetrioside, Catechin and Neridienone A are identified as candidates against Delta and Omicron for the first time.

Tweetable abstract

We report structure-based identification of natural compounds viz., Quercetin-3-acetyl-glucoside, Rutin, Kaempferol, Catechin, Orientin, Obetrioside and Neridienone A against SARS-CoV-2 Mpro, Helicase and Spike as well as Delta and Omicron Spike proteins.

Keywords::

• antivirals
• Delta
• helicase
• Mpro
• natural products
• Omicron
• SARS-CoV-2
• Spike

Financial & competing interests disclosure

The authors acknowledge the Researchers Supporting Project (no. RSP2023R379), King Saud University, Riyadh, Saudi Arabia for funding this work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The authors acknowledge the Researchers Supporting Project (no. RSP2023R379), King Saud University, Riyadh, Saudi Arabia for funding this work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.