STUDY OF THE INHIBITION POTENTIAL OF REMDESIVIR DERIVATIVES ON MPRO OF SARS-COV-2

Aluísio Marques Da Fonseca,Antonio Luthierre Gama Cavalcante,Rubson Mateus Matos Carvalho,Moises Maia Neto,Emmanuel Silva Marinho,Regilany Paulo Colares,Jeferson Falcão Do Amaral

doi:10.29121/granthaalayah.v8.i11.2020.2342

Abstract

The emergence of the new coronavirus (SARS-COV-2) is known to trigger some common diseases in humans such as pneumonia and diarrhea, the search for appropriate therapy combat COVID-19 has been intense and exhaustive. Motivation/Background: Thus, based on the rational study of drugs, a survey of potential ligands that can inhibit the vital protein in virus replication, the main protease (Mpro), has been carried out worldwide. Method: In this battle, the antiviral Remdesivir, which was created to fight the Ebola virus, proved, through the molecular anchorage, to be quite effective against its target because it presented affinity energy far superior to its co-crystallized ligand. Results: In this work, a study was carried out with Remdesivir and its derivatives, obtained in a zinc database15, to present a possible alternative, based on its structure-affinity, as potential Inhibitors of SARS-COV-2 MPro, with affinity energy ranging from -6.3 to -8.2 kcal/mol. Conclusions: It was found that both remdesivir and its diastereoisomeric derivatives have an affinity with the main protease (Mpro), responsible for viral replication, with inhibition capacity and possible alternative in its treatment.

Highlights

The year 2020 will forever be marked as necessary for public health due to the emergence of the new coronavirus's pandemic, belonging to a family of viruses called Coronaviridae, known to trigger some common diseases in humans such as colds and diarrhea. [1], [2], [3], [4]Over the past 20 years, Coronavirus has been responsible for two significant pandemics, severe acute respiratory syndrome (SARS)-CoV, 2002, and the Middle East Respiratory Syndrome (MERS)–CoV in 2012
It was found that both remdesivir and its diastereoisomeric derivatives have an affinity with the main protease (Mpro), responsible for viral replication, with inhibition capacity and possible alternative in its treatment
This work aims to study in silico of Remdesivir and its constitutional and diastereoisomeric derivatives to verify its interaction with Mpro protease and be based on new studies, with potential inhibitors for SARS-COV-2 and treatment of COVID-19

Summary

Introduction

The year 2020 will forever be marked as necessary for public health due to the emergence of the new coronavirus's pandemic, belonging to a family of viruses called Coronaviridae, known to trigger some common diseases in humans such as colds and diarrhea. [1], [2], [3], [4]Over the past 20 years, Coronavirus has been responsible for two significant pandemics, severe acute respiratory syndrome (SARS)-CoV, 2002, and the Middle East Respiratory Syndrome (MERS)–CoV in 2012. The year 2020 will forever be marked as necessary for public health due to the emergence of the new coronavirus's pandemic, belonging to a family of viruses called Coronaviridae, known to trigger some common diseases in humans such as colds and diarrhea. [6] The first indications of this viral epidemic were reported in this city, where the health system interpreted some of the infected symptoms, diagnosing them with pneumonia. Some less common symptoms, such as loss of taste and smell, indicated that the diagnosis was not correct enough. These patients were submitted to several tests and interpreted their daily lives to seek similarities and finalize the diagnosis. With the spread and increase in the number of countries that confirmed the cases of COVID-19, on January 30, 2020, the WHO declared this as a Public Health Emergency of International Importance and on March 11, 2020, decreed a pandemic of this disease. [5]

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