Identification of Flavonoids of Kalanchoe Pinnata as Candidate Drugs for COVID-19 Gamma-Variant Treatment

Abstract

Treatment of COVID-19 that is based on plants could be a more cost-effective therapy against the disease. Flavonoids, a group of compounds that have been observed to have various effects, including antiviral activity, were chosen as the candidate molecule for treatment of COVID-19. Kalanchoe Pinnata is one of the plants containing flavonoids that has been demonstrated to have antiviral activity. The structure of ACE2 and various flavonoids were retrieved and cleaned from unnecessary residues. The ACE2 structure was subjected to molecular docking in order to analyze the binding affinity. Following that, the ADME properties of each flavonoid were analyzed accordingly. The QSAR analysis was also performed for each type of flavonoid. Lastly, molecular dynamics simulation was conducted. All of the tested compounds were able to bind to human ACE2 and SARS-CoV-2 Spike protein, but were unable to compete with them as the binding affinity of the compounds to the protein were lower compared to ACE2-Spike interaction. The ADME and toxicity analysis showed that most of the ligands were able to be absorbed by the GI tract, but have low bioavailability. The compounds also cause no major toxicity effects and were able to be sufficiently distributed to the body. Molecular dynamics analysis also revealed that among the compounds, quercetin and rutin were able to interact with ACE2 and Spike protein stably. The QSAR analysis showed that friedelin, kaempferol, quercetin, and rutin are mostly non-toxic, but the high Cramer values indicate that there are no initial safety impressions for these molecules and could cause toxicity. In conclusion, quercetin and rutin have potential to be a candidate for COVID-19 drug development based on the in-silico predictions results obtained. Friedelin and Narcissin whose affinity to the proteins were relatively stronger but had unstable interactions from molecular dynamics simulation results, may also be a potential COVID-19 treatment with further investigation. However, further research is required to assess the effectiveness and also specially to measure the toxicity of the compounds.

Introductory Chapter: Current Landscape of Animal and Human Virus Treatments

“…While highly promising, some therapeutic approaches are still in their infancy. The development of lead compounds for COVID-19 from natural products is currently still ongoing, mainly in both in vitro and in vivo stages [20]. Moreover, the same condition also occurred with siRNA-based therapeutics [21].…”

<i>In silico</i> Screening of Potential Antidiabetic Phenolic Compounds from Banana (<i>Musa</i> spp.) Peel Against PTP1B Protein

“…Ertiprotafib, which is a PTP1B inhibitor that has passed phase II clinical trial was used as standard in this study and its structure was retrieved from PubChem Database as well (Liu et al 2022). The ligands and standard were retrieved in SMILES (simplified molecular input line entry system) format for QSAR and ADME-Tox analysis, and .sdf format for molecular docking and molecular dynamics simulation (Aurora et al 2022). Their energy was minimized prior to docking and converted to .pdbqt format using OpenBabel wizard in PyRx (Wicaksono et al 2022).…”

An In Silico Study: Phytochemical Compounds Screening of Garcinia atroviridis Griff. ex T. Anders as Anti-DENV

“…Molecular dynamics was explored to know the stability of ligand-protein interactions. 29 This simulation conducted using CABS-flex 2.0 versionwebserver (http://biocomp.chem.uw.edu.…”