Title:In silico Screening of Phytoconstituents with Antiviral Activities Against SARS-COV-2 Main Protease, Nsp12 Polymerase, and Nsp13 Helicase Proteins
Volume: 18
Issue: 8
Author(s): Jainey Puthenveettil James, Divya Jyothi and Sneh Priya*
Affiliation:
- Department of Pharmaceutics, Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Deralakatte, Mangaluru-575018, Karnataka,India
Keywords:
Phytoconstituents, SARS-CoV-2 proteins, molecular docking, ADMET property, pharmacophore modeling, PASS
predictor.
Abstract:
Aims: The present study aimed to analyse the molecular interactions of the
phytoconstituents known for their antiviral activity with the SARS-CoV-2 nonstructural proteins
such as main protease (6LU7), Nsp12 polymerase (6M71), and Nsp13 helicase (6JYT). The
applied in silico methodologies were molecular docking and pharmacophore modeling using
Schrodinger software.
Methods: The phytoconstituents were taken from PubChem, and SARS-CoV-2 proteins were
downloaded from the protein data bank. The molecular interactions, binding energy, ADMET
properties, and pharmacophoric features were analysed by glide XP, prime MM-GBSA, qikprop,
and phase application of Schrodinger, respectively. The antiviral activity of the selected
phytoconstituents was carried out by PASS predictor online tools.
Results: The docking score analysis showed that quercetin 3-rhamnoside (-8.77 kcal/mol) and
quercetin 3-rhamnoside (-7.89 kcal/mol) were excellent products to bind with their respective
targets such as 6LU7, 6M71, and 6JYT. The generated pharmacophore hypothesis model validated
the docking results, confirming the hydrogen bonding interactions of the amino acids. The PASS
online tool predicted constituent's antiviral potentials.
Conclusion: The docked phytoconstituents showed excellent interactions with the SARS-CoV-2
proteins, and on the outset, quercetin 3-rhamnoside and quercetin 7-rhamnoside interacted well
with all the three proteins; these belong to the plant Houttuynia cordata. The pharmacophore
hypothesis has revealed the characteristic features responsible for their interactions, and PASS
prediction data has supported their antiviral activities. Thus, these natural compounds could be
developed as lead molecules for antiviral treatment against SARS-CoV-2. Further in-vitro and invivo
studies could be carried out to provide better drug therapy.
