The impact of curcumin derived polyphenols on the structure and flexibility COVID-19 main protease binding pocket: a molecular dynamics simulation study

Abstract

The newly occurred SARS-CoV-2 caused a leading pandemic of coronavirus disease (COVID-19). Up to now it has infected more than one hundred sixty million and killed more than three million people according to 14 May 2021 World Health Organization report. So far, different types of studies have been conducted to develop an anti-viral drug for COVID-19 with no success yet. As part of this, silico were studied to discover and introduce COVID-19 antiviral drugs and results showed that protease inhibitors could be very effective in controlling. This study aims to investigate the binding affinity of three curcumin derived polyphenols against COVID-19 the main protease (Mpro), binding pocket, and identification of important residues for interaction. In this study, molecular modeling, auto-dock coupled with molecular dynamics simulations were performed to analyze the conformational, and stability of COVID-19 binding pocket with diferuloylmethane, demethoxycurcumin, and bisdemethoxycurcumin. All three compounds have shown binding affinity −39, −89 and −169.7, respectively. Demethoxycurcumin and bisdemethoxycurcumin showed an optimum binding affinity with target molecule and these could be one of potential ligands for COVID-19 therapy. And also, COVID-19 main protease binding pocket binds with the interface region by one hydrogen bond. Moreover, the MD simulation parameters indicated that demethoxycurcumin and bisdemethoxycurcumin were stable during the simulation run. These findings can be used as a baseline to develop therapeutics with curcumin derived polyphenols against COVID-19.

Investigating Fungi-Derived Bioactive Molecules as Inhibitor of the SARS Coronavirus Papain Like Protease: Computational Based Study

“…Accordingly, all the bioactive compounds reported here showed docking scores higher than −7.4 kcal mol−1 which are higher than the reference drug ( Table 1 ). The computational screening technique offered a reasonable screening result from an array of drugs and phytochemicals as a credible inhibitor for target molecules ( 5 – 7 ). But, the protein folding reactions took place at an ms level, which was at the limit of the accessible simulation times.…”

“…Even though safe and effective vaccines are available to protect people from getting COVID-19, there is no effective inhibitor for the SARS-CoV-2 protease to prevent people from being seriously ill or dying (1,2,4). At present, computeraided drug designs have been used as an efficient alternative for recognizing reliable candidates that can be repurposed drugs or/and phytochemicals to treat viral infection, including COVID-19 (5)(6)(7). Papain-like protease (PLpro) is an essential coronavirus protein required for the processing of viral polyproteins to generate functional protein for virus replication and enable viral spread; therefore, the inhibition of the PLpro is a feasible strategy to develop antiviral drugs and suppress the ongoing SARS-CoV-2 impacts (3)(4)(5).…”

“…At present, computeraided drug designs have been used as an efficient alternative for recognizing reliable candidates that can be repurposed drugs or/and phytochemicals to treat viral infection, including COVID-19 (5)(6)(7). Papain-like protease (PLpro) is an essential coronavirus protein required for the processing of viral polyproteins to generate functional protein for virus replication and enable viral spread; therefore, the inhibition of the PLpro is a feasible strategy to develop antiviral drugs and suppress the ongoing SARS-CoV-2 impacts (3)(4)(5). Furthermore, they are unique to the different viruses including COVID-19, thus offering the potential for specific treatments that produce minimal toxic side effects (5).…”

“…Papain-like protease (PLpro) is an essential coronavirus protein required for the processing of viral polyproteins to generate functional protein for virus replication and enable viral spread; therefore, the inhibition of the PLpro is a feasible strategy to develop antiviral drugs and suppress the ongoing SARS-CoV-2 impacts (3)(4)(5). Furthermore, they are unique to the different viruses including COVID-19, thus offering the potential for specific treatments that produce minimal toxic side effects (5). Therefore, SARS-CoV-2 PLpro makes it an attractive antiviral drug target but, there is a limited study to address this area.…”

Unveiling the Effect of Low pH on the SARS-CoV-2 Main Protease by Molecular Dynamics Simulations

“…Likewise, new advances in pH-dependence have shown the importance of appropriate histidine protonation states of SARS-CoV-2 Mpro in the coupling with inhibitors [55]. In the last two years, different SARS-CoV-2 inhibitors have been studied, such as synthetic and natural compounds [28,[56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71].…”