Identification of SARS-CoV-2 Spike Protein Inhibitors from Urtica Dioica to Develop Herbal-Based Therapeutics Against COVID-19

Abstract

Objective: The high transmission rate and mutations of SARS-CoV-2 have made it a global pandemic, and the shortage of any effective clinical treatment has created such a commotion. There are some synthetic antiviral drugs, such as remdesivir and lopinavir that are being repurposed to treat SARS-CoV-2, but all of these demonstrate extreme side effects in humans. Hence, promoting herbal-based drug development has become crucial as they are cost-effective and have lesser or no side effects. Urtica dioica is abundant in the Himalayan region and the compounds present in it have shown significant antiviral and anti-SARS activity. Therefore, molecular docking studies were performed to identify SARS-CoV-2 spike protein inhibitors from U. dioica to combat the COVID-19 disease. Materials and Methods: Compounds from U. dioica were screened using the bioinformatic approach, and subsequently, these compounds were docked with the S1 subunit of the COVID-19 spike protein (PDB ID: 6YOR). Molecular docking was carried out using the PyRx software (0.8 version) and further examined by employing the Discovery Studio Visualizer. Results: About all the selected compounds showed significant binding energy (e.g., beta-sitosterol: −10.3 kcal/mol) in contrast to the control chloroquine phosphate. This binding was observed with the spike protein residues that were common in the old strain and the more contagious newly modified B.1.1.7 strain of SARS-CoV-2. Conclusions: Thus, our study can be used in effective drug development against SARS-CoV-2 and its mutant strains also.

Drug repurposing: identification of SARS-CoV-2 potential inhibitors by virtual screening and pharmacokinetics strategies

“…The S-protein can mutate within short periods, and targeting these proteins is quite challenging to prevent such infections. Three phyto-compounds, deoxyartemisinin, deoxypodophyllotoxin, and dictamnine, were studied by Irfan et al [45]. They observed low binding energies of these compounds with the S-protein of SARS-CoV-2.…”

Identification of novel inhibitors from Urtica spp against TNBC targeting JAK2 receptor for breast cancer therapy

“…Thus, nding an alternative form of treatment is of utmost importance. Uttarakhand Himalaya has been known to be a uent in traditional plants that have been reported to be effective against a range of human diseases [14][15][16][17]. Herbs like Urtica or Stinging nettle are among the most common, multi-purpose plants that have not been exploited to their full potential yet.…”

“…B-Possible treatment: Modulation of the JAK2/STAT3 pathway- (12,13,14) The herbal-based compounds viz., the Polar compounds, are thought to act by targeting the JAK 2 associated receptor, besides non-polar, and mid polar compounds are thought to target JAK2, and STAT3, (15) thus modulating the upregulated activity of JAK 2. (16,17,18) This results in the normal phosphorylation, and dimerization of STAT 3. (19) These dimers are then translocated into the nucleus in normal amount, (20) resulting in the modulated expression of STAT 3 target genes, leading to normal cell survival.…”

“…Herbal-based compounds, due to the least side effects [12,13]can be employed in the treatment of TNBC via targeting the JAK2 receptor. Urtica, a plant of the Uttarakhand Himalayan with potential anticancer and antiviral properties [14][15][16][17], can be exploited to develop treatment regimens for TNBC. Hence, moving in this direction, we collected two species of Urtica (U. dioica, and U. parvi ora) from different regions of Uttarakhand, followed by preparation of its leaf and stem extracts in polar (ethanol), mid-polar (chloroform), and nonpolar (hexane) solvents utilizing the Soxhlet extraction technique.…”