Computational drug discovery: Exploring natural products targeting SARS-CoV-2

Ikoma, Japan—The COVID-19 pandemic highlighted the urgent need for effective therapeutic agents against SARS-CoV-2. Although vaccines helped control the spread of the virus, the emergence of new variants continues to challenge global health efforts. Small-molecule inhibitors targeting viral proteins could serve as an effective alternative for controlling the spread of COVID-19 at both individual and community levels.

In this vein, a recent study led by Associate Professor Md. Altaf-Ul-Amin, along with Muhammad Alqaaf, Ahmad Kamal Nasution, Mohammad Bozlul Karim, Mahfujul Islam Rumman, Naoaki Ono, and Shigehiko Kanaya from the Nara Institute of Science and Technology (NAIST), Japan, as well as Muhammad Hendrick Sedayu and Retno Supriyanti from Jenderal Soedirman University, Indonesia, explored natural products as potential inhibitors of the SARS-CoV-2 spike protein using computational methods.

As described in their paper published in Volume 15 of Scientific Reports on January 2, 2025, the research team employed molecular docking analysis to screen a diverse library of natural compounds that could act against the spike proteins. By simulating interactions at the atomic level, they identified several promising molecules with high binding affinities. Such compounds can interfere with viral entry mechanisms, thereby reducing viral activity.

“The variants of spike proteins can be divided into five distinct clusters based on the similarity of their amino acid sequences and functions,” revealed Associate Professor Md. Altaf-Ul-Amin. He further added, “This clustering was performed using an in-house developed algorithm and software named DPClusSBO, which helped to effectively classify the spike proteins.” Additionally, the natural products screened in this study were sourced from the KNApSAcK database, which was also developed at the research team’s laboratory. This database contains a comprehensive dataset of natural products useful for drug discovery.

A total of 11 natural compounds were identified: cephaeline, emetine, uzarigenin, linifolin A, caffeine, colchamine, cytidine, (+)-epijasmonic acid, 11-hydroxyvittatine, staurosporin, and paxilline. Among them, caffeine was particularly noteworthy, as it is commonly found in coffee and caffeinated beverages. Molecular docking along with other analyses revealed that caffeine binds strongly to the spike protein’s active site and exhibits high binding stability. Notably, a drug appropriateness analysis suggested that caffeine possesses excellent solubility and significant potential as an oral drug candidate.

The discovery that a widely known and consumed compound such as caffeine functions as a SARS-CoV-2 inhibitor presents an interesting therapeutic possibility. In addition to its potential against viral invasion, caffeine plays a dual role in a wide range of medical applications owing to its neuroprotective and anticancer effects. These properties underscore its versatility and demonstrate its potential positive impact on global health. “Our findings highlight the potential of natural products in the fight against COVID-19. The identified compounds provide a basis for further experimental validation and drug development strategies,” explains Muhammad Alqaaf, first author of the study.

This research contributes to the broader field of computational drug discovery by demonstrating how bioinformatics and molecular modeling can accelerate the identification of novel viral inhibitors. Future research will focus on the in vitro and in vivo validation of the identified compounds, as well as potential structural modifications to enhance their antiviral activity.

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Resource

Title: Discovering natural products as potential inhibitors of SARS-CoV-2 spike proteins

Authors: Muhammad Alqaaf, Ahmad Kamal Nasution, Mohammad Bozlul Karim, Mahfujul Islam Rumman, Muhammad Hendrick Sedayu, Retno Supriyanti, Naoaki Ono, Md. Altaf-Ul-Amin, and Shigehiko Kanaya

Journal: Scientific Reports

DOI: 10.1038/s41598-024-83637-4

Information about the Computational Systems Biology can be found at the following website: https://isw3.naist.jp/Research/ai-csb-en.html

About Nara Institute of Science and Technology (NAIST)

Established in 1991, Nara Institute of Science and Technology (NAIST) is a national university located in Kansai Science City, Japan. In 2018, NAIST underwent an organizational transformation to promote and continue interdisciplinary research in the fields of biological sciences, materials science, and information science. Known as one of the most prestigious research institutions in Japan, NAIST lays a strong emphasis on integrated research and collaborative co-creation with diverse stakeholders. NAIST envisions conducting cutting-edge research in frontier areas and training students to become tomorrow's leaders in science and technology.