The Novel Drug Discovery to Combat COVID-19 by Repressing Important Virus Proteins Involved in Pathogenesis Using Medicinal Herbal Compounds

Abstract

Background: The cause of COVID-19 global pandemic is SARS-CoV-2. Given the outbreak of this disease, it is so important to find a treatment. One strategy to cope with COVID-19 is to use the active ingredients of medicinal plants. In this study, the effect of active substances was surveyed in inhibiting four important druggable targets, including S protein, 3CLpro, RdRp, and N protein. RdRp controls the replication of SARS-CoV-2 and is crucial for its life cycle. 3CLpro is the main protease of the virus and could be another therapeutic target. Moreover, N protein and S protein are responsible for SARS-CoV-2 assembly and attaching, respectively.

Methods: The 3D structures of herbal active ingredients were prepared and docked with the mentioned SARS-CoV-2 proteins to obtain their affinity. Then, available antiviral drugs introduced in other investigations were docked using similar tools and compared with the results of this study. Finally, other properties of natural compounds were uncovered for drug designing.

Results: The outcomes of the study revealed that Linarin, Amentoflavone, (-)-Catechin Gallate and Hypericin from Chrysanthemum morifolium, Hypericum perforatum, Humulus lupulus, and Hibiscus sabdariffa had the highest affinity for these basic proteins and in some cases, their affinity was much higher than antiviral medicines.

Conclusion: In addition to having high affinity, these herb active ingredients have antioxidant, vasoprotective, anticarcinogenic, and antiviral properties. Therefore, they can be used as extremely safe therapeutic compounds in drug design studies to control COVID-19.

Keywords: COVID-19; Drug design; Medicinal plants; SARS-CoV-2.

Figure 1.

Affinity of top scoring medicinal herbal compounds to inhibit the S protein, 3CLpro, RdRp, and N protein. A) the interaction between Amentoflavone from Hypericum perforatum (Purple) and S protein (Orange red); B) the interaction between Linarin from Chrysanthemum morifolium (Deep pink) and N protein (Light sea green); C) the interaction between Amentoflavone from Hypericum perforatum (Orang) and 3CLpro (Olive drab); D) the interaction between Amentoflavone from Hypericum perforatum (Violet red) and RdRp (Sandy brown).