In silico studies identify potent plant metabolites capable of inhibiting SARS-CoV-2

The continual emergence of new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been prolonging the coronavirus disease 2019 (COVID-19) pandemic. These variants emerge due to the evolution of the SARS-CoV-2 genome. 

Study: An integrated computational approach towards the screening of active plant metabolites as potential inhibitors of SARS-CoV-2: an overview. Image Credit: Gorodenkoff /


Over the past two decades, three severe pathogenic zoonotic disease outbreaks have been caused by Beta coronaviruses. These include SARS-CoV-2, SARS-CoV-1, and the Middle East respiratory syndrome coronavirus (MERS-CoV). Among all coronavirus epidemics, SARS-CoV-2 has had the most significant impact on the global healthcare system and economy.

To date, all available COVID-19 vaccines and therapeutics have been developed based on the spike (S) protein of the ancestral SARS-CoV-2 strain. Unfortunately, these vaccines exhibit reduced efficacy against specific SARS-CoV-2 variants, such as the Omicron and Delta variants that contain mutations in the S region. As a result, scientists worldwide are still working to develop more effective vaccines and therapeutics to protect individuals from contracting SARS-CoV-2.

Throughout the COVID-19 pandemic, several drugs have been repurposed to treat this disease; however, many are associated with severe side effects. For example, heparin, azithromycin, hydroxychloroquine, ritonavir, atazanavir, and clozapine manifest severe side effects associated with the cardiovascular and hematopoietic systems.

Plants and their derivatives have been a key source of medicines and food for many years. According to a recent study, around 80% of the world's population depends on plants to stay healthy.

Unlike synthetic drugs, most plant-based products used for medicinal purposes exhibit minimal side effects. Therefore, plant metabolites could be a potent source for providing alternative therapy for SARS-CoV-2 infection.

About the study

Molecular docking is a well-known in silico method that predicts the interlink between molecules and biological targets. Studies involving molecular docking estimate the ligand's molecular similarities with a receptor and calculate a docking score.

Previously, in silico methods have been used to discover novel molecules to inhibit SARS-CoV-2 replication. These molecules were then purposed by analyzing the binding efficacy of the plant's secondary metabolites against the active sites of target viral proteins.

A recent Structural Chemistry journal study reviews the importance of in silico studies based on the binding efficacy of phytoconstituents against active sites of SARS-CoV-2.

The current systemic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 233 studies were obtained from PubMed. Plant metabolites identified in this review were further analyzed for their drug-likeness using the Molsoft database.

Inhibition of SARS-CoV-2 using bioactive phytoconstituents

The SARS-CoV-2 genome consists of a 5′ untranslated region, which includes a 5′ leader sequence, open reading frame encoding non-structural proteins, structural proteins including the S, envelope €, membrane (M), and nucleocapsid (N), accessory proteins, and a 3′ untranslated region. These proteins can be targeted to develop novel drugs.

Different phytochemicals exhibited varying binding effectiveness with SARS-CoV-2 targets. Interestingly, many bioactive phytochemicals demonstrated their efficacy in binding to numerous proteins.

Based on available in silico docking studies, 100 bioactive phytoconstituents were identified that could inhibit SARS-CoV-2. Phytochemical classes that can effectively bind to SARS-CoV-2 active protein sites include coumarins, flavonoids, steroids, and alkaloids. Among these, flavonoids exhibited a maximum inhibitory effect against SARS-CoV-2 and high binding energy.

Several phytoconstituents exhibited high docking scores, such as curcumin, apigenin, chrysophanol, emodin, gingerol, gallate, and zingerone. In addition, these molecules inhibited the S glycoprotein with higher binding energy.

Similar binding energy was observed in some drugs approved by the United States Food and Drug Administration (FDA) to treat COVID-19, including doxycycline, ivermectin, and azithromycin. This suggests that phytoconstituents could significantly contribute to the management of COVID-19; however, more preclinical and clinical studies are required to validate this finding.

About 70% of the bioactive phytoconstituents, including laurolistine, avicularin, and acetoside, can bind with the main protease (Mpro) of SARS-CoV-2. These bioactive metabolites could also bind to a lesser extent with SARS-CoV-2 proteins. This observation indicated that Mpro could be used as a potential target to develop future COVID-19 therapeutics.

Belachinal, a phytoconstituent, can be chemically modified and analyzed for its ani-SARS-CoV-2 properties. This compound targets the SARS-CoV-2 E protein.

Other compounds, such as macaflavanone E and vibsabol B, demonstrated similar binding energy to synthetic drugs that bind to the E protein. Some phytoconstituents that target ACE-2 include absinthin, avicularin, and hispidulin. 

Future perspectives

Based on existing literature, the authors highlight some research gaps that could be improved in the future. For example, most phytoconstituents identified to be effective against SARS-CoV-2 require chemical modification, which could be explored in future work. In addition, in vivo analyses are needed to validate the study findings.

Journal reference:
  • Kushari, S., Hazarika, I., Laloo, D. et al. (2022). An integrated computational approach towards the screening of active plant metabolites as potential inhibitors of SARS-CoV-2: an overview. Structural Chemistry. doi:10.1007/s11224-022-02066-z

Posted in: Drug Discovery & Pharmaceuticals | Medical Research News | Disease/Infection News | Pharmaceutical News

Tags: Atazanavir, Azithromycin, Compound, Coronavirus, Coronavirus Disease COVID-19, covid-19, Curcumin, Drugs, Efficacy, Evolution, Food, Genome, Glycoprotein, Healthcare, Heparin, Hydroxychloroquine, in vivo, Ivermectin, Ligand, Membrane, MERS-CoV, Metabolites, Omicron, Pandemic, Phytochemical, Preclinical, Protein, Receptor, Research, Respiratory, Ritonavir, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Syndrome, Therapeutics

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Written by

Dr. Priyom Bose

Priyom holds a Ph.D. in Plant Biology and Biotechnology from the University of Madras, India. She is an active researcher and an experienced science writer. Priyom has also co-authored several original research articles that have been published in reputed peer-reviewed journals. She is also an avid reader and an amateur photographer.

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