In silico Study Phytosterol Cymbopogon citratus and Curcuma longa as Inhibitor Agent 3C-Like Protease SARS-CoV-2

Abstract

Background and Objective: Lemongrass (Cymbopogon citratus) and turmeric (Curcuma longa) are widely used by the community for traditional medicinal spices and cooking spices. In the era of the COVID-19 pandemic, people use lemongrass and turmeric to increase immunity and protect the body from infection with the SARS-CoV-2 virus. However, the antiviral mechanisms have not been studied much. This study aims to predict the bioactivity of the phytosterol compounds of lemongrass and turmeric for COVID-19 therapy through inhibition of 3C-like protease (3CLPro) in silico. Materials and Methods: The 3CLPro protein 3D structure was downloaded from the PDB database with the access code 2ZU2 and the phytosterol compounds of lemongrass and turmeric were taken from PubChem. A total of 59 total phytosterol compounds from turmeric and lemongrass were screened for their bioactivity as an antiviral by using online PASS.Compounds with a high activating potential (Pa) were interacted with 3CLPro protein with the PyRx program and analyzed by Discovery Studio version 19.0 and LigPlus. Results: A total of 22 total phytosterol compounds were identified as potential antiviral agents. Based on the Pa value, 15 phytosterol compounds have the potential to act as inhibitor agents for 3CLPro SARS-CoV-2. The phytosterol compounds of lemongrass and turmeric bind to the 3CLPro protein in the N-finger domain region and the A and B domain inhibitors connect residues of the 3CLPro protein. The phytosterols of lemongrass and turmeric show a low binding affinity with 3CLPro SARS-CoV-2, indicating a strong interaction between ligand and protein. The inhibition of phytosterols against 3CLPro protein can be used as a basis for determining candidates for COVID-19 therapeutic agents. Conclusion: The phytosterol compounds contained in lemongrass and turmeric have the potential to act as 3CLPro inhibitors. Further studies both in vitro and in vivo need to be done to prove the inhibitory potential of phytosterol compounds.

In silico screening for potential inhibitors from the phytocompounds of Carica papaya against Zika virus NS5 protein

“…Phytosterols are naturally occurring plant molecules with a structure similar to cholesterol, 70 and they have been demonstrated to possess the antiviral activity of several sterols against the spike protein of the COVID-19 virus and influenza-A virus. 63,71 Our study identified several phytosterols, including β-sitosterol and Δ7-avenasterol, demonstrating potent inhibitory affinity (Figure 3A). Earlier studies have also shown the potential health benefits, including antiviral effects of β-sitosterol, which has been shown to reduce the infectivity of the hepatitis-B virus and HIV, possibly by hindering the attachment of viruses to host cells.…”

“…For instance, Sinefungin is a small molecule that has been shown to inhibit the MTase activity of several flaviviruses. 63 However, the study showed a low potency of Sinefungin on NS5 of ZIKV compared to other flaviviruses' MTase domain; additionally, the toxicity associated with the particular drug had raised concern about its use. 64 Hydrogen bonding and hydrophobic interactions are crucial in facilitating significant ligand binding at the active site residues of the receptor in docked complexes.…”

In silico screening for potential inhibitors from the phytocompounds of Carica papaya against Zika virus NS5 protein

“…Phytosterols are naturally occurring plant molecules with a structure similar to cholesterol, 62 and they have been demonstrated to possess antiviral activity of several sterols against the spike protein of the COVID-19 virus and influenza-A virus. 56,63 Our study identified several phytosterols, including β-sitsterol and Δ7-avenasterol, demonstrating potent inhibitory affinity (Figure 3A). Earlier studies have also shown the potential health benefits including antiviral effects of β-sitosterol, which has been shown to reduce the infectivity of the hepatitis-B virus and HIV, possibly by hindering the attachment of viruses to host cells.…”

“…For instance, Sinefungin is a small molecule that has been shown to inhibit the MTase activity of several flaviviruses. 56 However, the study showed a low potency of Sinefungin on NS5 of ZIKV compared to other flaviviruses' MTase domain; additionally, the toxicity associated with the particular drug had raised concern about its use. 57 Hydrogen bonding and hydrophobic interactions are crucial in facilitating significant ligand binding at the active site residues of the receptor in docked complexes.…”