In Silico Evaluation of Iranian Medicinal Plant Phytoconstituents as Inhibitors against Main Protease and the Receptor-Binding Domain of SARS-CoV-2

Abstract

The novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initially appeared in Wuhan, China, in December 2019. Elderly individuals and those with comorbid conditions may be more vulnerable to this disease. Consequently, several research laboratories continue to focus on developing drugs to treat this infection because this disease has developed into a global pandemic with an extremely limited number of specific treatments available. Natural herbal remedies have long been used to treat illnesses in a variety of cultures. Modern medicine has achieved success due to the effectiveness of traditional medicines, which are derived from medicinal plants. The objective of this study was to determine whether components of natural origin from Iranian medicinal plants have an antiviral effect that can prevent humans from this coronavirus infection using the most reliable molecular docking method; in our case, we focused on the main protease (Mpro) and a receptor-binding domain (RBD). The results of molecular docking showed that among 169 molecules of natural origin from common Iranian medicinal plants, 20 molecules (chelidimerine, rutin, fumariline, catechin gallate, adlumidine, astragalin, somniferine, etc.) can be proposed as inhibitors against this coronavirus based on the binding free energy and type of interactions between these molecules and the studied proteins. Moreover, a molecular dynamics simulation study revealed that the chelidimerine–Mpro and somniferine–RBD complexes were stable for up to 50 ns below 0.5 nm. Our results provide valuable insights into this mechanism, which sheds light on future structure-based designs of high-potency inhibitors for SARS-CoV-2.

Computational prediction of the effect of mutations in the receptor-binding domain on the interaction between SARS-CoV-2 and human ACE2

“…Some of them are repurposed antiviral medications that have been approved by the Food and Drug Administration (FDA) [21,22]. Other initiatives include the search for drugs that are derived from medicinal plants [23][24][25].…”

Fruit Bromelain-Derived Peptide Potentially Restrains the Attachment of SARS-CoV-2 Variants to hACE2: A Pharmacoinformatics Approach

“…The toxicity analysis considered several parameters, including the LD 50 , predicted toxicity class, hepatotoxicity, carcinogenicity, immunotoxicity, mutagenicity, and cytotoxicity. Toxicity levels are classified as follows: classes 1 and 2 (fatal if swallowed), class 3 (toxic if swallowed), class 4 (harmful if swallowed), class 5 (possibly harmful if swallowed), and class 6 (nontoxic) [ 58 ]. The predicated LD 50 of the peptide is 500 mg/kg, which classified the molecule in class 4, indicating it is harmful if swallowed.…”

Elucidating the Glucokinase Activating Potentials of Naturally Occurring Prenylated Flavonoids: An Explicit Computational Approach

“…A lesser hydrogen bonding interaction and higher hydrophobic interaction signified that the latter have a greater contribution to the binding affinity and stability of a ligand in an enzyme’s binding pocket [ 25 ]. In this study, only one hydrogen bonding interaction was observed for arcommunol B, manuifolin H, and kuwanon F, while none was observed for kuwanon S. This indicated that hydrophobic interaction was more prevalent and contributed exceedingly to the binding affinity and stability of the ligands in the glucokinase enzyme’s binding pocket.…”