Computational Studies on T2Rs Agonist-Based Anti-COVID-19 Drug Design.

Premnath Dhanaraj,Samiha Nuzhat,Mahtabin Rodela Rozbu,Mosae Selvakumar Paulraj,Indiraleka Muthiah

doi:10.3389/fmolb.2021.637124

Premnath Dhanaraj, Samiha Nuzhat + Show 3 more

Open Access

https://doi.org/10.3389/fmolb.2021.637124

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Abstract

The expeditious and world pandemic viral disease of new coronavirus (SARS-CoV-2) has formed a prompt urgency to discover auspicious target-based ligand for the treatment of COVID-19. Symptoms of novel coronavirus disease (COVID-19) typically include dry cough, fever, and shortness of breath. Recent studies on many COVID-19 patients in Italy and the United Kingdom found increasing anosmia and ageusia among the COVID-19-infected patients. SARS-CoV-2 possibly infects neurons in the nasal passage and disrupts the senses of smell and taste, like other coronaviruses, such as SARS-CoV and MERS-CoV that could target the central nervous system. Developing a drug based on the T2Rs might be of better understanding and worth finding better molecules to act against COVID-19. In this research, we have taken a taste receptor agonist molecule to find a better core molecule that may act as the best resource to design a drug or corresponding derivatives. Based on the computational docking studies, the antibiotic tobramycin showed the best interaction against 6LU7 COVID-19 main protease. Aromatic carbonyl functional groups of the molecule established intermolecular hydrogen bonding interaction with GLN189 amino acid and it showed the two strongest carbonyl interactions with receptor protein resulting in a glide score of −11.159. To conclude, depending on the molecular recognition of the GPCR proteins, the agonist molecule can be recognized to represent the cell secondary mechanism; thus, it provides enough confidence to design a suitable molecule based on the tobramycin drug.

Highlights

A new strain of single-stranded RNA virus, belonging to the Coronoviridae family, brought the world to a halt, presenting 2020 with the coronavirus pandemic
Considering the corresponding drug developmentrelated challenges and association of bitter taste receptors with SARS-CoV-2, this study aims to predict a suitable structure for a drug molecule that may have suitable molecular recognition with G-protein–coupled receptors (GPCR) proteins
The study used Schrödinger docking software to seek core molecules that can efficiently inhibit the pathway of COVID19 pathogen as it invades cellular membranes, spreading within the body

Summary

Introduction

A new strain of single-stranded RNA virus, belonging to the Coronoviridae family, brought the world to a halt, presenting 2020 with the coronavirus pandemic. HCoV-229E, HCoV-OC43, SARS-CoV or SARS-CoV-1, SARS-CoV-2, MERS-CoV (Middle East respiratory syndrome coronavirus), HCoVNL63, and HCoV-HKU1 are seven members known (to date) to be part of the coronavirus family (Nichols et al, 2008; Song et al, 2019; Su S et al, 2016; Kuek and Lee, 2020). HCoV-229E and HCoV-OC43 have been widely studied, known to cause mild flu-like symptoms, unlike the pathogenic SARS-CoV, SARS-CoV-2, and MERS-CoV strains that can induce serious respiratory distress and pneumonia and be fatal (Su S et al, 2016; Song Z et al, 2019; Mason, 2020 ). Other common symptoms of COVID-19 infection include respiratory dysfunctions, fever, aches, tiredness, and coughing so on (Ul Qamar et al, 2020)

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