key: cord-0830723-sco615i1
authors: Hussain, Afzal; Hussain, Ashfaq
title: Computational repurposing of asthma drugs as potential inhibitors of SARS-cov-2 mpro
date: 2022-04-11
journal: New Microbes New Infect
DOI: 10.1016/j.nmni.2022.100979
sha: 37abe59ddda92bff070a79daecaa724c2dd904e4
doc_id: 830723
cord_uid: sco615i1

nan

COVID-19, new viral pneumonia, was initially discovered in China and expanded rapidly throughout the world. COVID-19 had affected over 472,816,657 as of March 23, 2022, as shown in a WHO press release, with over 6,099,380 deaths. The rate of infection and numbers of deaths continues to rise, and no verified medications or authorized new drugs have so far been discovered. As a result, the progress of an anti-COVID-19 had become a worldwide health crisis. The main protease (M pro ) of the COVID-19 virus is liable for the proteolysis of replicase polyproteins, as a result of development of a variety of functional proteins required for viral replication as well as transcription [1] . The dearth of directly linked homologues in humans, as well as M pro's functional importance in the viral life cycle, makes it an interesting target for antiviral medicines [2] . Even though multiple papers on SARS-CoV M pro have been published, no protease new inhibitor has yet to move to the preclinical stage. Since then, researchers have shown a unique X-ray structure of SARS-CoV-2 M pro in conjunction including reversible dipeptide inhibitor X77. Even so, to our understanding, this final crystal structure was never used for virtual drug database screening against Asthma Drugs. According to a study from Oxford University, early treatment with the asthma drug budesonide can diminish the serious risk of rigorous SARS-CoV-2 illness and shorten the time to recovery. There are presently no specific target drugs available, and effective therapy alternatives are limited [3] . Reportedly, there is no medication for COVID-19, and research into the infection's therapy, particularly vaccines, is currently in progress. Remdesivir and ritonavir are two clinical candidates which have obtained a lot more attention [4] . Even though it was specifically introduced as a stand-alone antiviral, it was shown to be effective when used in combination with low-dose ritonavir and also other protease inhibitors. As a result, the process of discovering new antiviral drugs is extremely difficult, costly, and time-consuming. Screening existing compounds intended for COVID-19 therapy is an appealing strategy for rapidly identifying highly promising drug candidates with already-optimized pharmacokinetics and minimal toxic side effects [5] . Therefore, computeraided drug design (CADD) procedures have been identified as a viable solution. Structure-based virtual screening (SBVS) utilizing molecular docking study has conclusively demonstrated to be a very excellent technique for antiviral and antibacterial drug development becoming an important starting point in the finding of new lead compounds for the treatment of various diseases. SBVS was used in this research on Asthma drugs. The Schrödinger software suite was used to define a docking framework against the target protein. The goal is to develop novel SARS-CoV-2 major protease (M pro ) inhibitors with high binding interaction in the binding site as well as binding pocket stability. This study aimed to discover potential inhibitors of COVID-19's main protease using a compounds screening, followed by ADMET and MMGBSA assessment to discover novel inhibitors that could be used as potential leads for medicating coronavirus infections.

The COVID-19 disease harmed everyday life. One in every five people in the world is thought to be at greater risk for developing severe COVID-19 infection due to underlying health issues. Repurposing existing medications could be a great way to reach therapeutic interventions demonstrated to be safe and effective in clinical trials. We identified asthma medications that can be powerful inhibitors of the COVID-19 M pro on the basis of molecular docking. Asthma drugs Vilanterol and Salmeterol attach to the COVID-19 main protease's active site and shown tight interaction than the Reference ligand X77 and the drug budesonide (studied by Oxford University). The docking score of Vilanterol (-8.727) and Salmeterol (-8.635) is also high than J o u r n a l P r e -p r o o f X77 (-7.640) and drug budesonide (-6.077). As a result, these drug candidates could be promising Anti COVID M pro agents. However, to confirm inhibition activity, these drugs must be evaluated using in-vitro methods. 

Characteristics of SARS-CoV-2 and COVID-19

COVID-19: The first documented coronavirus pandemic in history

Treatment options for COVID-19: The reality and challenges

Remdesivir versus ritonavir/lopinavir in COVID-19 patients

A Computer-Aided Drug Design Approach to Predict Marine Drug-Like Leads for SARS-CoV-2 Main Protease Inhibition

The authors want to acknowledge the Department of Bioinformatics, MANIT, for providing the research facility to complete the research work. They are also thankful to the Schrodinger team for providing the software facility.