Molecular docking and pharmacokinetic studies of phytocompounds from Nigerian Medicinal Plants as promising inhibitory agents against SARS-CoV-2 methyltransferase (nsp16)

Abstract

Background Since the index case was reported in China, COVID-19 has led to the death of at least 4 million people globally. Although there are some vaccine cocktails in circulation, the emergence of more virulent variants of SARS-CoV-2 may make the eradication of COVID-19 more difficult. Nsp16 is an S-adenosyl-L-Methionine-dependent methyltransferase that plays an important role in SARS-CoV-2 viral RNA cap formation—a crucial process that confers viral stability and prevents virus detection by cell innate immunity mechanisms. This unique property makes nsp16 a promising molecular target for COVID-19 drug design. Thus, this study aimed to identify potent phytocompounds that can effectively inhibit SARS-CoV-2 nsp16. We performed in silico pharmacokinetic screening and molecular docking studies using 100 phytocompounds—isolated from fourteen Nigerian plants—as ligands and nsp16 (PDB: 6YZ1) as the target. Results We found that only 59 phytocompounds passed the drug-likeness analysis test. However, after the docking analysis, only six phytocompounds (oxopowelline, andrographolide, deacetylbowdensine, 11, 12-dimethyl sageone, sageone, and quercetin) isolated from four Nigerian plants (Crinum jagus, Andrographis paniculata, Sage plants (Salvia officinalis L.), and Anacardium occidentale) showed good binding affinity with nsp16 at its active site with docking score ranging from − 7.9 to − 8.4 kcal/mol. Conclusions Our findings suggest that the six phytocompounds could serve as therapeutic agents to prevent viral survival and replication in cells. However, further studies on the in vitro and in vivo inhibitory activities of these 6 hit phytocompounds against SARS-CoV-2 nsp16 are needed to confirm their efficacy and dose.

In Silico and In Vitro Analyses of Multiple Terpenes Predict Cryptotanshinone as a Potent Inhibitor of the Omicron Variant of SARS-CoV-2

“…Based on the significant binding energy and substantial hydrogen bond interactions in addition to the hydrophobic interactions with key residues of S1-RBD, the compounds were screened. To reduce the possibility of false-positive results, the docking protocol was verified by re-docking and superimposition methods (RMSD ≤ 2 Å), which guaranteed the correctness and consistency of the docking results [34,35]…”

In Silico Study of Coumarins: Wedelolactone as a Potential Inhibitor of the Spike Protein of the SARS-CoV-2 Variants

“…To ensure the accuracy and reliability of docking as well as to get rid of falsepositive results, the docking protocol was validated using the methods of redocking and superimposition [24,25]. First, one of the reference ligands, molnupiravir, was docked within the designated binding sites of the Omicron spike protein.…”