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.

Hypericum perforatum and Its Ingredients Hypericin and Pseudohypericin Demonstrate an Antiviral Activity against SARS-CoV-2

“…Furthermore, pre-treatments of cells do not block virus infectivity, arguing against a Hypericum perforatum -mediated blockade of the SARS-CoV-2 receptor ACE2. On the other hand, potential modes of antiviral actions of Hypericum perforatum against SARS-CoV-2 were introduced, since hypericin and pseudohypericin were anticipated, by molecular docking, to form a stable complex with the main (3CL) protease or the RNA polymerase of the SARS-CoV-2 [ 62 , 63 ] or had a high affinity toward SARS-CoV-2 basic proteins [ 64 ] but with only little clarification about biological evidence so far. However, it was found that some plant polyphenols could inhibit the 3CL protease using certain experimental settings [ 65 ].…”

Hypericum perforatum and Its Potential Antiplatelet Effect

“…In 2008, a review by Cochrane concluded that the results using plant extracts of HP were superior to placebo in patients with major depression, and were equally effective as standard antidepressants with fewer side effects [ 22 , 23 ]. Also, antioxidant, vasoprotective, anticarcinogenic, and antiviral properties of HP have been described [ 24 , 25 ].…”

Linarin, a Glycosylated Flavonoid, with Potential Therapeutic Attributes: A Comprehensive Review

“…Moreover, N and S proteins are responsible for SARS-CoV-2 assembly and attachment, respectively. Molecular docking outcomes of the study revealed that LN, amentoflavone, (-)-catechin gallate, and hypericin had an affinity for these basic proteins, which possess an effective role in SARS-CoV-2 infection [123].…”