Computational investigation on natural quinazoline alkaloids as potential inhibitors of the main protease (Mpro) of SARS_CoV_2

The recent outbreak of the highly contagious coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2 has created a global health crisis with socioeconomic impacts. Although, recently, vaccines have been approved for the prevention of COVID-19, there is still an urgent need for the discovery of more efficacious and safer drugs especially from natural sources. In this study, a number of quinoline and quinazoline alkaloids with antiviral and/or antimalarial activity were virtually screened against three potential targets for the development of drugs against COVID-19. Among seventy-one tested compounds, twenty-three were selected for molecular docking based on their pharmacokinetic and toxicity profiles. The results identified a number of potential inhibitors. Three of them, namely, norquinadoline A, deoxytryptoquivaline, and deoxynortryptoquivaline, showed strong binding to the three targets, SARS-CoV-2 main protease, spike glycoprotein, and human angiotensin-converting enzyme 2. These alkaloids therefore have promise for being further investigated as possible multitarget drugs against COVID-19.

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In Silico Identification of Potential Inhibitors of the Main Protease of SERS-CoV-2 Using Combined Ligand-based and Structure-based Drug Design approach

Eurasian Journal of Medicine and Oncology ◽

10.14744/ejmo.2020.91768 ◽

2020 ◽

Author(s):

Sudhan Debnath

Keyword(s):

Drug Design ◽

In Silico ◽

Design Approach ◽

Structure Based Drug Design ◽

Main Protease ◽

In Silico Identification ◽

Potential Inhibitors

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A Potential Peptide From Soy Cheese Produced Using Lactobacillus delbrueckii WS4 for Effective Inhibition of SARS-CoV-2 Main Protease and S1 Glycoprotein

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2020.601753 ◽

2020 ◽

Vol 7 ◽

Author(s):

Rounak Chourasia ◽

Srichandan Padhi ◽

Loreni Chiring Phukon ◽

Md Minhajul Abedin ◽

Sudhir P. Singh ◽

...

Keyword(s):

Drug Targets ◽

Docking Studies ◽

Lactobacillus Delbrueckii ◽

Amino Acid Residues ◽

Main Protease ◽

Effective Inhibition ◽

Cheese Peptides ◽

Potential Inhibitors

The COVID-19 pandemic caused by novel SARS-CoV-2 has resulted in an unprecedented loss of lives and economy around the world. In this study, search for potential inhibitors against two of the best characterized SARS-CoV-2 drug targets: S1 glycoprotein receptor-binding domain (RBD) and main protease (3CLPro), was carried out using the soy cheese peptides. A total of 1,420 peptides identified from the cheese peptidome produced using Lactobacillus delbrueckii WS4 were screened for antiviral activity by employing the web tools, AVPpred, and meta-iAVP. Molecular docking studies of the selected peptides revealed one potential peptide “KFVPKQPNMIL” that demonstrated strong affinity toward significant amino acid residues responsible for the host cell entry (RBD) and multiplication (3CLpro) of SARS-CoV-2. The peptide was also assessed for its ability to interact with the critical residues of S1 RBD and 3CLpro of other β-coronaviruses. High binding affinity was observed toward critical amino acids of both the targeted proteins in SARS-CoV, MERS-CoV, and HCoV-HKU1. The binding energy of KFVPKQPNMIL against RBD and 3CLpro of the four viruses ranged from −8.45 to −26.8 kcal/mol and −15.22 to −22.85 kcal/mol, respectively. The findings conclude that cheese, produced by using Lb. delbrueckii WS4, could be explored as a prophylactic food for SARS-CoV-2 and related viruses. In addition, the multi-target inhibitor peptide, which effectively inhibited both the viral proteins, could further be used as a terminus a quo for the in vitro and in vivo function against SARS-CoV-2.

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