ABSTRACT
Zingiber officinale, Curcuma longa, and Momordica charantia are medicinal plants that are commonly used in the form of herbal tea, which is formulated to strengthen the immune system, especially against COVID-19 infection. Excellent antioxidant, anti-inflammatory, and immunostimulatory properties have been reported for their bioactive compounds, which have been shown to aid in stimulating immune systems as well as lowering the risk of severe COVID-19 such as lung injury. Yet, no bibliometric study on the subject is available. Hence, the purpose of this study is to quantitatively examine the existing articles related to the therapeutic potential of these three herbs, as well as their mechanisms of action in combating the SARS-CoV-2 virus. A total of 121 papers were retrieved from Scopus database up to 14th March 2023. The bibliometric analysis was conducted using VOSviewer software. Based on the literature search, Z. officinale was the most researched plant. India appeared as the most prolific country, with the highest number of articles contributed by two authors from India (Rathi, R. and Gayatri Devi, R.). In terms of keywords, the plants were associated with immune modulation, management of symptoms, antioxidant, anti-inflammatory and antiviral activities. Several important bioactive compounds were responsible for these effects such as gingerol, paradol, shogaol, curcumin, calebin A, momordicoside, karaviloside and cucurbitadienol. These compounds were hypothesized to prevent and cure COVID-19 by regulating inflammatory response, downregulating oxidative stress and modulating immunostimulatory activity. This review paper therefore supports the potential of Z. officinale, C. longa, and M. charantia to be formulated as a herbal blend for treating and preventing COVID-19 infection.
ABSTRACT
COVID-19 is a disease that puts most of the world on lockdown and the search for therapeutic drugs is still ongoing. Therefore, this study used in silico screening to identify natural bioactive compounds from fruits, herbaceous plants, and marine invertebrates that are able to inhibit protease activity in SARS-CoV-2 (PDB: 6LU7). We have used extensive screening strategies such as drug likeliness, antiviral activity value prediction, molecular docking, ADME, molecular dynamics (MD) simulation, and MM/GBSA. A total of 17 compounds were shortlisted using Lipinski's rule in which 5 compounds showed significant predicted antiviral activity values. Among these 5, only 2 compounds, Macrolactin A and Stachyflin, showed good binding energy of -9.22 and -8.00 kcal/mol, respectively, within the binding pocket of the Mpro catalytic residues (HIS 41 and CYS 145). These two compounds were further analyzed to determine their ADME properties. The ADME evaluation of these 2 compounds suggested that they could be effective in developing therapeutic drugs to be used in clinical trials. MD simulations showed that protein-ligand complexes of Macrolactin A and Stachyflin with the target receptor (6LU7) were stable for 100 nanoseconds. The MM/GBSA calculations of Mpro-Macrolactin A complex indicated higher binding free energy (-42.58 ± 6.35 kcal/mol). Dynamic cross-correlation matrix (DCCM) and principal component analysis (PCA) on the residual movement in the MD trajectories further confirmed the stability of Macrolactin A bound state with 6LU7. In conclusion, this study showed that marine natural compound Macrolactin A could be an effective therapeutic inhibitor against SARS-CoV-2 protease (6LU7). Additional in vitro and in vivo validations are strongly needed to determine the efficacy and therapeutic dose of Macrolactin A in biological systems.