In-silico screening of plant-derived antivirals against main protease, 3CL^pro and endoribonuclease, NSP15 proteins of SARS-CoV-2

Abstract

Novel Coronavirus or SARS-CoV-2 outbreak has developed a pandemic condition all over the world. The virus is highly infectious and spreads by human to human local transmission mode. Till date, there is no vaccination or drugs been approved for the treatment by the World Health Organisation. Henceforth, the discovery of the potential drugs is an urgent and utmost requirement for the medical fraternity. Since, the side effects of plant-derived compounds will be lower compared to synthetic/ chemical drugs. The Main protease (3CL pro or NSP5) and endoribonuclease (NSP15) proteins are necessity for viral replication and its survival in the host cell. In the present study, in-silico approach of drug development was used to search for potential antiviral plant-derived compounds as inhibitors against SARS-CoV-2 replication proteins. Eight plant-derived compounds of which the antiviral activity was known and available, and two reported drugs against SARS-CoV-2 selected for the molecular docking analysis. The docking results suggested that bisdemethoxycurcumin, demethoxycurcumin, scutellarin, quercetin and myricetin showed least binding energy, i.e., greater than À6.5 Kcal/mol against 3CL pro and endoribonuclease of SARS-CoV-2. Further studies of ADME-Tox and bioavailability of drugs were also performed that exhibited efficient parameters of drug likeness. Molecular dynamics simulation calculations were performed for the most negative binding affinity of the compound to evaluate the dynamic behavior,and stability of protein-ligand complex. Our findings suggest that these compounds could be potential inhibitors of SARS-CoV-2 main protease and endoribonuclease. However, further invitro and pre-clinical experiments would validate the potential inhibitors of SARS-CoV-2 proteins.

Scutellaria barbata D. Don Inhibits the Main Proteases (Mpro and TMPRSS2) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection

“…As a major compound of SB, scutellarin has exhibited NLRP3 inflammasome suppression, thereby rescuing mice from bacterial sepsis [ 55 ]. In addition, a silico screening report of scutellarin revealed M pro inhibitory effects, supporting our study results [ 56 ]. Meanwhile, baicalein, which is a flavone extracted from the roots of Scutellaria baicalensis and Scutellaria lateriflora , has exhibited notable anti-oxidant, anti-virus, anti-bacteria, anti-inflammatory, anti-cancer, and immunoregulatory effects [ 57 , 58 , 59 ].…”

A systems-based method to repurpose marketed therapeutics for antiviral use: a SARS-CoV-2 case study

“…The SARS-CoV-2 protein with the top-ranked drug repurposing opportunities was Nsp15. Nsp15 is of particular interest as a drug target because it is an endoribonuclease common to all coronaviruses, is necessary for SARS-CoV-2 replication and interferes with host immune responses ( 51 , 52 , 53 , 54 , 55 , 56 , 57 ).…”

Next-generation computational tools and resources for coronavirus research: From detection to vaccine discovery

“…Using integrated molecular modeling approaches, various reports indicated that phytochemicals such as carvacrol, oleanolic acid, and ursolic acid, might act as probable inhibitors in modulating the M pro protein function and regulating replication of virus [ 129 ]. A computational study has hypothesized that plant-origin compounds viz., bisdemethoxycurcumin, demethoxycurcumin, scutellarin, myricetin, and quercetin could act as possible drug candidates against M pro and NSP15 proteins of SARS-CoV-2 [ 130 ].Further, repurposed existing drugs viz., disulfiram, carmofur, ebselen, shikonin, tideglusib, PX-12, and TDZD-8 might be promising inhibitors targeting M pro [ 131 ]. Similarly, Isavuconazonium (triazole), α-KI (ketoamide), and Pentagastrin (peptide) are suggested as possible drug candidates to treat infected patients with COVID-19 [ 132 ].Currently, several worldwide research organizations and pharmaceutical companies are steadily involved in developing an effective vaccine against the virulent SARS-CoV-2 virus [ 133 ].…”