Traditional medicinal plants against replication, maturation and transmission targets of SARS-CoV-2: computational investigation

Abstract

COVID-19 is an infectious pandemic caused by the SARS-CoV-2 virus. The critical components of SARS-CoV-2 are the spike protein (S-protein) and the main protease (M pro ). M pro is required for the maturation of the various polyproteins involved in replication and transcription. S-protein helps the SARS-CoV-2 to enter the host cells through the angiotensin-converting enzyme 2 (ACE2). Since ACE2 is required for the binding of SARS-CoV-2 on the host cells, ACE2 inhibitors and blockers have got wider attention, in addition to S-protein and M pro modulators as potential therapeutics for COVID-19. So far, no specific drugs have shown promising therapeutic potential against COVID-19. The current study was undertaken to evaluate the therapeutic potential of traditional medicinal plants against COVID-19. The bioactives from the medicinal plants, along with standard drugs, were screened for their binding against S-protein, M pro and ACE2 targets using molecular docking followed by molecular dynamics. Based on the higher binding affinity compared with standard drugs, bioactives were selected and further analyzed for their pharmacological properties such as drug-likeness, ADME/ T -test, biological activities using in silico tools. The binding energies of several bioactives analyzed with target proteins were relatively comparable and even better than the standard drugs. Based on Lipinski factors and lower binding energies, seven bioactives were further analyzed for their pharmacological and biological characteristics. The selected bioactives were found to have lower toxicity with a higher GI absorption rate and potent anti-inflammatory and anti-viral activities against targets of COVID-19. Therefore, the bioactives from these medicinal plants can be further developed as phytopharmaceuticals for the effective treatment of COVID-19.

Promising phytochemicals of traditional Himalayan medicinal plants against putative replication and transmission targets of SARS-CoV-2 by computational investigation

“…These SARS-CoV-2 target proteins have been used in several investigations to identify therapeutics against COVID-19 [ 13 , [18] , [19] , [20] , [21] ]. The protein molecules were processed by removing crystallographic water molecules, adding polar hydrogens, followed by stabilizing the charges as demonstrated earlier [ 22 , 23 ]. Finally, the three-dimensional coordinates were converted into PDBQT format using ADT [ 12 ].…”

“…Molecular docking was carried out using AutoDock-Vina [ 24 ]. Grid boxes were created around the active sites of SARS-CoV-2 3CL pro , PLpro, RdRp, helicase, and the interacting crucial residues of the SARS-CoV-2 spike protein-human ACE2 receptor complex using Autodock tools with dimensions relative to the ligands (XYZ) with a resolution of 1 Å [ 22 , 23 , 25 ]. Each docking calculation was performed three-times using different seeds and retaining the remaining values as default.…”

“…3D stereo figures of protein-ligand interactions were computed using PyMOL ( https://pymol.org/2 ). Further, the inhibition constant (Ki) for HMP bioactives with SARS-CoV-2 protein targets was calculated using the following equation [ 23 , 26 ]. Ki = 10 (Binding energy/1.366) …”

Nature Potential for COVID-19: Targeting SARS-CoV-2 Mpro Inhibitor with Bioactive Compound

“…Previous studies also showed that natural compounds can interact with the catalytic site of M pro proteases at HIS41 and CYS145 [24,29]. Previous research indicated that binding energy of -7.0 kcal/mol or less could be effective against SARS-CoV-2 which causes COVID-19 [26].…”

β-Caryophyllene, A Natural Dietary CB2 Receptor Selective Cannabinoid can be a Candidate to Target the Trinity of Infection, Immunity, and Inflammation in COVID-19

“…Despite recent availability of vaccine for prophylaxis, massive efforts are ongoing for the discovery of novel drugs for the treatment and prevention of COVID-19 (Jean and Hsueh, 2020;Kandeel and Al-Nazawi, 2020;Rabaan et al, 2020;Singh et al, 2020). In parallel with repurposing modern medicines, there are numerous attempts to explore natural products with potential to target the interplay of viral infection and immune-inflammatory axis (Bahramsoltani and Rahimi, 2020;Basu et al, 2020;Benarba and Pandiella, 2020;Hensel et al, 2020;Mondal et al, 2020;Narkhede et al, 2020). Over the past few months it has been suggested that natural products hold great promise in the management of COVID-19 due to their antiviral, anti-inflammatory, and immunomodulator activities (Bahramsoltani and Rahimi, 2020;Basu et al, 2020;Benarba and Pandiella, 2020;Mondal et al, 2020;Narkhede et al, 2020).…”