Molecular docking analysis of selected phytochemicals on two SARS-CoV-2 targets

Abstract

Background: The coronavirus spike (S) glycoprotein and M protease are two key targets that have been identified for vaccines and drug development against COVID-19. Methods: Virtual screening of some compounds of plant origin that have shown antiviral activities were carried out on the two targets, the M protease (PDB ID 6LU7) and S glycoprotein (PDB ID 6VSB), by docking with PyRx software. The binding affinities were compared with other compounds and drugs already identified as potential ligands for the M protease and S glycoprotein, as well as chloroquine and hydroxychloroquine. The docked compounds with best binding affinities were also filtered for drug likeness using the SwissADME and PROTOX platforms on the basis of physicochemical properties and toxicity, respectively. Results: The docking results revealed that scopadulcic acid and dammarenolic acid had the best binding affinity for the S glycoprotein and Mpro protein targets, respectively. Silybinin, through molecular docking, also demonstrated good binding affinity for both protein targets making it a potential candidate for further evaluation as repurposed candidate for SARS-CoV-2, with likelihood of having multitarget activity as it showed activities for both targets. Conclusions: The study proposes that scopadulcic acid and dammarenolic acid be further evaluated in vivo for drug formulation against SARS-COV-2 and possible repurposing of Silybinin for the management of COVIV-19.

Improvements in HOMA indices and pancreatic endocrinal tissues in type 2-diabetic rats by DPP-4 inhibition and antioxidant potential of an ethanol fruit extract of Withania coagulans 

“…ADMET analysis ADME/T (Absorption, distribution, Metabolism, Excretion, and Toxicity) analysis was performed using Drulito software (www.niper.gov.in/pi_dev_tools/DruLiToWeb /DruLiTo_index.html) to study the pharmacokinetics pro le of the identi ed compounds for potential drug development [47,48]. The compounds were ranked based on two lters: the Lipinski rule and the ability to pass through the blood brain barrier (BBB).…”

Novel Method for Detection of Genes With Altered Expression Caused by Coronavirus Infection and Screening of Candidate Drugs for SARS-CoV-2

“…Pioglitazone was also included in the list of candidate compounds for SARS-CoV-2 screened by an in silico method [19]. Quercetin was reported to inhibit the cell entry of SARS-CoV-2 [20], and was also included in the list of candidate compounds for SARS-CoV-2 screened by an in silico method [21]. Fenretinide was also included in the drugs identified as effective compounds in the "Drug perturbations from GEO up" category as described above.…”

“…Finally, we compared the drugs screened out using our approach from the "Drug perturbations from GEO up/down" lists with those screened from two in silico drug discovery studies [19], [21] 1) Comparison with Wu et al [19]: We found multiple hits, which are summarized in Table X. The main drugs identified included doxycycline, ascorbic acid, isotretinoin, pioglitazone, cortisone, and tibolone.…”

“…2) Comparison with Ubani et al [21]: Ubani et al [21] screened a library of 22 phytochemicals with antiviral activity obtained from the PubChem database for activity against the spike envelope glycoprotein and main protease of SARS-CoV-2. Among these, we found only one hit that overlapped with our screened out drugs, which was quercetin (Table XI).…”

“…OF in silico SCREENED DRUGS[21] WHOSE TARGET GENES ARE ALSO ENRICHED IN THE 134 GENES SELECTED BY TD BASED UNSUPERVISED FE.…”