J. Pharm. Pharmacogn. Res., vol. 12, no. 2, pp. 371-381, Mar-Apr 2024.
DOI: https://doi.org/10.56499/jppres23.1806_12.2.371
Original Article
Kaempferia parviflora Wall. ex Baker against SARS-CoV-2 spike protein: In silico and in vitro studies
[Kaempferia parviflora Wall. ex Baker contra la proteína de la espiga del SARS-CoV-2: Estudios in silico e in vitro]
Suhaina Supian*, Muhamad Aizuddin Ahmad, Lina Rozano, Zuraida Ab Rahman
Biotechnology and Nanotechnology Research Centre, Malaysian Agricultural Research and Development Institute (MARDI), Serdang 43400, Selangor, Malaysia.*E-mail: suhaina@mardi.gov.my
Abstract
Context: SARS-CoV-2 spike (S) protein, governed by its receptor binding domain (RBD), is a key player in mediating viral attachment and fusion into host cells, which leads to infection and transmission of COVID-19. Searching for effective inhibitors against S RBD protein is essential to stop the virus infection.
Aims: To evaluate Kaempferia parviflora’s bioactive compounds as inhibitors against SARS-CoV-2 S RBD protein and its complex with human angiotensin-converting enzyme 2 (ACE2) receptor through in silico, and to determine the ability of K. parviflora’s extract to inhibit the binding of S RBD and ACE2.
Methods: Molecular docking was performed to evaluate the inhibition potentials of K. parviflora’s bioactive compounds against S RBD protein and its complex with ACE2. The inhibitory activity of K. parviflora’s extract against the binding of S RBD and ACE2 was determined using an in vitro inhibition assay.
Results: K. parviflora’s compounds had inhibition potentials against S RBD protein in both closed and open states. In the open RBD, these compounds were bound to the key amino acids that were involved in the binding of RBD with ACE2, suggesting their possible roles in preventing the RBD-ACE2 association. K. parviflora’s compounds also had strong affinities towards the S RBD-ACE2 complex by interacting with the paired RBD-ACE2 amino acids, which were crucial for the S RBD-ACE2 complex’s stability. In addition, K. parviflora extract also demonstrated inhibitory activity against the binding of S RBD and ACE2.
Conclusions: This study proposes K. parviflora as a promising inhibitor against SARS-CoV-2 S protein for the treatment of COVID-19.
Keywords: angiotensin-converting enzyme 2; bioactive compounds; COVID-19; molecular docking; plant extracts.
Resumen
Contexto: La proteína spike (S) del SARS-CoV-2, gobernada por su dominio de unión al receptor (RBD), es un actor clave en la mediación de la unión y fusión viral en las células huésped, lo que conduce a la infección y transmisión del COVID-19. La búsqueda de inhibidores eficaces contra la proteína S RBD es esencial para detener la infección del virus.
Objetivos: Evaluar in silico los compuestos bioactivos de Kaempferia parviflora como inhibidores de la proteína S RBD del SARS-CoV-2 y su complejo con el receptor humano de la enzima convertidora de angiotensina 2 (ACE2), y determinar la capacidad del extracto de K. parviflora para inhibir la unión de S RBD y ACE2.
Métodos: Se realizó un acoplamiento molecular para evaluar los potenciales de inhibición de los compuestos bioactivos de K. parviflora frente a la proteína S RBD y su complejo con ACE2. La actividad inhibitoria del extracto de K. parviflora frente a la unión de S RBD y ACE2 se determinó mediante un ensayo de inhibición in vitro.
Resultados: Los compuestos de K. parviflora presentaron potenciales de inhibición frente a la proteína S RBD tanto en estado cerrado como abierto. En la RBD abierta, estos compuestos se unieron a los aminoácidos clave implicados en la unión de la RBD con ACE2, lo que sugiere su posible papel en la prevención de la asociación RBD-ACE2. Los compuestos de K. parviflora también mostraron una gran afinidad hacia el complejo S RBD-ACE2 al interaccionar con los aminoácidos emparejados RBD-ACE2, cruciales para la estabilidad del complejo S RBD-ACE2. Además, el extracto de K. parviflora también demostró actividad inhibidora contra la unión de S RBD y ACE2.
Conclusiones: Este estudio propone a K. parviflora como un prometedor inhibidor de la proteína S del SARS-CoV-2 para el tratamiento de la COVID-19.
Palabras Clave: acoplamiento molecular; compuestos bioactivos; COVID-19; enzima convertidora de angiotensina 2; extractos vegetales.
Citation Format: Supian S, Ahmad MA, Rozano L, Ab Rahman Z (2024) Kaempferia parviflora Wall. ex Baker against SARS-CoV-2 spike protein: In silico and in vitro studies. J Pharm Pharmacogn Res 12(2): 371–381. https://doi.org/10.56499/jppres23.1806_12.2.371
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