Abstract
Our earlier experimental and computational report produced evidence on the antiviral nature of the compound seselin purified from the leaf extracts of Aegle marmelos against Bombyx mori Nuclear Polyhedrosis Virus (BmNPV). In the pandemic situation of COVID-19 caused by the SARS-COV-2 virus, an in silico effort to evaluate the potentiality of the seselin was made to test its efficacy against multiple targets of SARS-COV-2 such as spike protein S2, COVID-19 main protease and free enzyme of the SARS-CoV-2 (2019-nCoV) main protease. The ligand seselin showed the best interaction with receptors, spike protein S2, COVID-19 main protease and free enzyme of the SARS-CoV-2 (2019-nCoV) main protease with a binding energy of −6.3 kcal/mol, −6.9 kcal/mol and −6.7 kcal/mol, respectively. Docking analysis with three different receptors identified that all the computationally predicted lowest energy complexes were stabilized by intermolecular hydrogen bonds and stacking interactions. The amino acid residues involved in interactions were ASP1184, GLU1182, ARG1185 and SER943 for spike protein, SER1003, ALA958 and THR961 for COVID-19 main protease, and for SARS-CoV-2 (2019-nCoV) main protease, it was THR111, GLN110 and THR292. The MD simulation and MM/PBSA analysis showed that the compound seselin could effectively bind with the target receptors. The outcome of pharmacokinetic analysis suggested that the compound had favourable drugability properties. The results suggested that the seselin had inhibitory potential over multiple SARS-COV-2 targets and hold a high potential to work effectively as a novel drug for COVID-19 if evaluated in experimental setups in the foreseeable future. Communicated by Ramaswamy H. Sarma
Highlights
The outbreak of corona virus disease 2019 (COVID-19) disease recently has transitioned into pandemic state and consumed numerous human lives due to its contagious nature
In the pandemic situation of COVID-19 caused by SARS-COV-2 virus, an in silico effort to evaluate the potentiality of the seselin has been made to test its efficacy against multiple targets of SARS-COV-2 such as SARS-CoV-2S spike protein, COVID-19 main protease and free enzyme of the SARS-CoV-2 (2019-nCoV) main protease
Formation of hydrogen bonding was observed by the molecule seselin with THR111 and GLN110 residues of SARS-CoV-2S protein (Fig. 3)
Summary
The outbreak of corona virus disease 2019 (COVID-19) disease recently has transitioned into pandemic state and consumed numerous human lives due to its contagious nature This dreadful disease has infected more than 3.15 million people and the reported deaths have been over 0.22 million, till date [World Health Organization (WHO), Coronavirus, COVID-19 update - https://covid19.who.int/]. Particular attention has been given to spike protein and proteases of SARS-CoV-2 [3] This is because, upon the molecular studies on virus transmission, it is evident that i) the spike protein binds to the host cellular receptor angiotensin converting enzyme-2 (ACE2) and responsible for the fusion between the viral envelope and the cellular membrane ii) the proteolytic cleavage of polyprotein by a papain‐like cysteine protease and 3C‐like serine protease forms the replication enzymes of virus [4,5,6,7]. The resulted information of reported docking studies highly facilitates the categorization of drugs and takes a call on proceedings with potential candidates for in vitro and follow up studies
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