scholarly journals In Silico Identification and Validation of Organic Triazole Based Ligands as Potential Inhibitory Drug Compounds of SARS-CoV-2 Main Protease

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6199
Author(s):  
Vishma Pratap Sur ◽  
Madhab Kumar Sen ◽  
Katerina Komrskova
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Pharmacokinetic Parameters ◽  
Drug Molecules ◽  
Main Protease ◽  
Ready Availability ◽  
In Silico Identification ◽  
Inhibitory Drug ◽  
High Binding Affinity

The SARS-CoV-2 virus is highly contagious to humans and has caused a pandemic of global proportions. Despite worldwide research efforts, efficient targeted therapies against the virus are still lacking. With the ready availability of the macromolecular structures of coronavirus and its known variants, the search for anti-SARS-CoV-2 therapeutics through in silico analysis has become a highly promising field of research. In this study, we investigate the inhibiting potentialities of triazole-based compounds against the SARS-CoV-2 main protease (Mpro). The SARS-CoV-2 main protease (Mpro) is known to play a prominent role in the processing of polyproteins that are translated from the viral RNA. Compounds were pre-screened from 171 candidates (collected from the DrugBank database). The results showed that four candidates (Bemcentinib, Bisoctrizole, PYIITM, and NIPFC) had high binding affinity values and had the potential to interrupt the main protease (Mpro) activities of the SARS-CoV-2 virus. The pharmacokinetic parameters of these candidates were assessed and through molecular dynamic (MD) simulation their stability, interaction, and conformation were analyzed. In summary, this study identified the most suitable compounds for targeting Mpro, and we recommend using these compounds as potential drug molecules against SARS-CoV-2 after follow up studies.

In Silico Exploration of Molecular Mechanism and Potency Ranking of Clinically Oriented Drugs for Inhibiting SARS-CoV-2’s Main Protease

2020 ◽  
Author(s):  
Tien Huynh ◽  
haoran wang ◽  
Binquan Luan
Keyword(s):  
Ligand Binding ◽  
In Silico ◽  
Fast Response ◽  
Binding Mechanism ◽  
Biological Functions ◽  
Drug Molecules ◽  
Global Pandemic ◽  
Main Protease ◽  
Potency Ranking ◽  
High Binding Affinity

<p>Currently, the new coronavirus disease 2019 (COVID-19) is a global pandemic without any well calibrated treatment. To inactivate the SARS-CoV-2 virus that causes COVID-19, the main protease (Mpro) that performs key biological functions in the virus has been the focus of extensive studies. With the fast-response experimental efforts, the crystal structures of Mpro of the SARS-CoV-2 virus have just become available recently. Herein, we theoretically investigated the binding mechanism between the Mpro's pocket and various marketed drug molecules being tested in clinics to fight COVID-19 that show promising outcomes. Combining all existing experiment results with our computational ones, we revealed an important ligand-binding mechanism for the Mpro that the binding stability of a ligand inside the Mpro pocket can be significantly improved if the partial ligand occupies the so-called "anchor" site of the Mpro. Along with the high-potent drugs/molecules (such as nelfinavir and curcumin) revealed in this study, the newly discovered binding mechanism paves the way for further optimizations and designs of Mpro's inhibitors with a high binding affinity. </p>

scholarly journals In Silico Exploration of Molecular Mechanism and Potency Ranking of Clinically Oriented Drugs for Inhibiting SARS-CoV-2’s Main Protease

2020 ◽  
Author(s):  
Tien Huynh ◽  
haoran wang ◽  
Binquan Luan
Keyword(s):  
Ligand Binding ◽  
In Silico ◽  
Fast Response ◽  
Binding Mechanism ◽  
Biological Functions ◽  
Drug Molecules ◽  
Global Pandemic ◽  
Main Protease ◽  
Potency Ranking ◽  
High Binding Affinity

<p>Currently, the new coronavirus disease 2019 (COVID-19) is a global pandemic without any well calibrated treatment. To inactivate the SARS-CoV-2 virus that causes COVID-19, the main protease (Mpro) that performs key biological functions in the virus has been the focus of extensive studies. With the fast-response experimental efforts, the crystal structures of Mpro of the SARS-CoV-2 virus have just become available recently. Herein, we theoretically investigated the binding mechanism between the Mpro's pocket and various marketed drug molecules being tested in clinics to fight COVID-19 that show promising outcomes. Combining all existing experiment results with our computational ones, we revealed an important ligand-binding mechanism for the Mpro that the binding stability of a ligand inside the Mpro pocket can be significantly improved if the partial ligand occupies the so-called "anchor" site of the Mpro. Along with the high-potent drugs/molecules (such as nelfinavir and curcumin) revealed in this study, the newly discovered binding mechanism paves the way for further optimizations and designs of Mpro's inhibitors with a high binding affinity. </p>

scholarly journals Potential of NO donor furoxan as SARS-CoV-2 main protease (Mpro) inhibitors: in silico analysis

2020 ◽  
pp. 1-15 ◽  
Author(s):  
Abdullah G. Al-Sehemi ◽  
Mehboobali Pannipara ◽  
Rishikesh S. Parulekar ◽  
Omkar Patil ◽  
Prafulla B. Choudhari ◽  
...  
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
No Donor ◽  
Main Protease ◽  
Silico Analysis

scholarly journals In silico analysis of Phyllanthus amarus phytochemicals as potent drugs against SARS-CoV-2 main protease

2021 ◽  
pp. 100159
Author(s):  
T.P. Krishna Murthy ◽  
Trupthi Joshi ◽  
Shivani Gunnan ◽  
Nidhi Kulkarni ◽  
Priyanka V ◽  
...  
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Phyllanthus Amarus ◽  
Main Protease ◽  
Silico Analysis

scholarly journals In silico analysis and identification of promising hits against 2019 novel coronavirus 3C-like main protease enzyme

2020 ◽  
pp. 1-14 ◽  
Author(s):  
Shilpa Chatterjee ◽  
Arindam Maity ◽  
Suchana Chowdhury ◽  
Md Ataul Islam ◽  
Ravi K. Muttinini ◽  
...  
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Protease Enzyme ◽  
Main Protease ◽  
Novel Coronavirus ◽  
Silico Analysis

scholarly journals In Silico Analysis of Sea Urchin Pigments as Potential Therapeutic Agents Against SARS-CoV-2: Main Protease (Mpro) as a Target.

2020 ◽  
Author(s):  
Tamara Rubilar ◽  
Elena Susana Barbieri ◽  
Ayelén Gázquez ◽  
Marisa Avaro ◽  
Mercedes Vera-Piombo ◽  
...  
Keyword(s):  
Sea Urchin ◽  
In Silico ◽  
De Novo ◽  
Drug Repurposing ◽  
In Silico Analysis ◽  
Promising Alternative ◽  
In Silico Docking ◽  
Main Protease

The SARS-CoV-2 outbreak has spread rapidly and globally generating a new coronavirus disease (COVID-19) since December 2019 that turned into a pandemic. Effective drugs are urgently needed and drug repurposing strategies offer a promising alternative to dramatically shorten the process of traditional de novo development. Based on their antiviral uses, the potential affinity of sea urchin pigments to bind main protease (Mpro) of SARS-CoV-2 was evaluated in silico. Docking analysis was used to test the potential of these sea urchin pigments as therapeutic and antiviral agents. All pigment compounds presented high molecular affinity to Mpro protein. However, the 1,4-naphtoquinones polihydroxilate (Spinochrome A and Echinochrome A) showed high affinity to bind around the Mpro´s pocket target by interfering with proper folding of the protein mainly through an H-bond with Glu166 residue. This interaction represents a potential blockage of this protease´s activity. All these results provide novel information regarding the uses of sea urchin pigments as antiviral drugs and suggest the need for further in vitro and in vivo analysis to expand all therapeutic uses against SARS-CoV-2. <br>

Sign in / Sign up

Export Citation Format

Share Document