PAPAIN LIKE PROTEASE: A POTENTIAL TARGET FOR MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS (MERS-COV): THE BATTLE CONTINUESAbstract
Middle-East Respiratory Syndrome coronavirus (MERS-CoV) can trigger severe acute pneumonia, renal, digestive failure and even death. Coronaviruses express papain-like proteases (PLpro), multipurpose enzymes which had protease activity and can lacerate nonstructural proteins to manipulate the viral polyprotein responsible for replication. They also have deubiquitinating function, which can modify the innate immune response. The reduction of the infection of MERS-CoV is by Inhibition of PLpro with a ligand will wedge the cleavage progression of nonstructural protein. As a result, papain-like protease may be considered as a candidate for antiviral drug production. This current study focuses on screening of extracts from Neem and Eucalyptus for MERS-CoV that could be potentially used as an inhibitor against the disease. Blind molecular docking study was conducted by using Auto Dock followed by visualization using PyMol, which is examined in this existing study. Deacetylgedunin (Neem) and eucalyptol (Eucalyptus) showed successful binding to MERS-CoV papain-like protease based on measured parameters such as root Mean Square Deviation (RMSD), binding capacity and inhibiting constant. The compound Deacetylgedunin found in neem exhibited the lowest RMSD value of 16.388 Å and the highest binding energy of –8.28 kcal/mol. It also had the highest inhibition constant value of 851.36 nM and the lowest inhibition constant value of 851.36 nM. Since Deacetylgedunin gave a better result compared to Indinavir, hence it can be considered as a potential and safe alternative for the current medicine given for MERS-CoV disease.
Neeldeep Ganguly, Swagata Roy and Tamalika Chakraborty *
Guru Nanak Institute of Pharmaceutical Science and Technology, 157/F, Nilgunj Road, Sodepur Panihati, Kolkata, India.
14 March 2022
02 May 2022
04 May 2022
01 November 2022