Comparative docking studies of drugs and phytocompounds for emerging variants of SARS-CoV-2

Abstract

In the last three years, COVID-19 has impacted the world with back-to-back waves leading to devastating consequences. SARS-CoV-2, the causative agent of COVID-19, was first detected in 2019 and since then has spread to 228 countries. Even though the primary focus of research groups was diverted to fight against COVID-19, yet no dedicated drug has been developed to combat the emergent life-threatening medical conditions. In this study, 35 phytocompounds and 43 drugs were investigated for comparative docking analysis. Molecular docking and virtual screening were performed against SARS-CoV-2 spike glycoprotein of 13 variants using AutoDock Vina tool 1.5.6 and Discovery Studio, respectively, to identify the most efficient drugs. Selection of the most suitable compounds with the best binding affinity was done after screening for toxicity, ADME (absorption, distribution, metabolism and excretion) properties and drug-likeliness. The potential candidates were discovered to be Liquiritin (binding affinities ranging between −7.0 and −8.1 kcal/mol for the 13 variants) and Apigenin (binding affinities ranging between −6.8 and −7.3 kcal/mol for the 13 variants) based on their toxicity and consistent binding affinity with the Spike protein of all variants. The stability of the protein-ligand complex was determined using Molecular dynamics (MD) simulation of Apigenin with the Delta plus variant of SARS-CoV-2. Furthermore, Liquiritin and Apigenin were also found to be less toxic than the presently used drugs and showed promising results based on in silico studies, though, confirmation using in vitro studies is required. This in-depth comparative investigation suggests potential drug candidates to fight against SARS-CoV-2 variants.

Phytochemicals in Drug Discovery - A Confluence of Tradition and Innovation

“…Liquiritin ( 14) (a repurposed drug) and apigenin (15) (a phytochemical) (Figure 9) emerged as top contenders based on docking score, ADMET analysis, and drug likeliness profiles. However, in vitro and in vivo studies are yet to be carried out to validate its potency [120]. Additionally, other phytochemicals, such as phenolics and terpenoids, have shown potential as leads, including quercetin, luteolin, and neoandrographolide (Figure 10) that were identified as potential inhibitors of SARS-CoV-2 druggable protein targets.…”

Fighting cytokine storm and immunomodulatory deficiency: By using natural products therapy up to now

“…On 21 March 2023, there are 761,071,826 confirmed COVID-19 cases worldwide, including 6,879,677 deaths reported to the WHO by national authorities, and has spread to 228 countries ( Chugh et al, 2023 ). Many studies indicate that in addition to the use of antiviral medicines to treat COVID-19, the reduction of the cytokine storm might be an effective therapeutic strategy for successfully combating the disease ( Rahmati and Moosavi, 2020 ).…”

“…A virus can activate the immune system (B-cells, T-cells, macrophages, neutrophil cells, dendritic cells, and monocytes cells) and resident tissue cells, producing massive amounts of pro-inflammatory cytokines ( Chugh et al, 2023 ). During a flu virus infection, innate immune responses are triggered by interferon (IFN)-stimulated gene regulation cascade amplification events, and IFN is mainly produced by macrophages, monocytes, and dendritic cells.…”

Anti-Staphylococcal, Anti-Candida, and Free-Radical Scavenging Potential of Soil Fungal Metabolites: A Study Supported by Phenolic Characterization and Molecular Docking Analysis

“…The ranking of binding interactions for each compound with the respective target proteins was based on factors such as the lowest energy and lowest RMSD (Root-Mean-Square Deviation). It is noteworthy that a lower binding energy score indicates better stability in the protein-ligand binding interaction [80].…”