A new corona virus, 2019-n-CoV, caused a pandemic of respiratory disease (COVID-19) in Wuhan city, has since spread worldwide [1]. The virus has been called as SARS CoV2, as the RNA genome of virus is 82% similar to the SARS coronavirus. Presently, no particular treatment for COVID 19 is accessible and research concerning the therapy of COVID-19 is undergoing [2]. Nevertheless, the processes that have been applied remain restricted to supportive and defensive therapies, intended to avoid additional obstacles and damage to organs. Certain primary investigations have scrutinized possible blends that comprise anti-malarial drug hydroxychloroquine, and Anti Human Immuno deficieny virus (HIV) vaccines could be used for treating COVID19 infections. Besides using antiviral drugs, clinicians are utilizing MERS CoV and SARS CoV neutralizing antibodies with a specific target on the domain “S1” of spike protein (glycoprotein) of the COVID 19 [3].
Like other corona viruses, the outer membrane spike glycoprotein, is the major protein involved in interaction with specific targets of host cell (for instance adhesion factors, Ezrin, CD26, ACE2 and cyclophilins). All these targets are significant for adhesion and virulence. As far as entry of corona viruses is concerned, it is facilitated via transmembrane “S” glycoprotein that produces homo-trimer projecting from surface of virus [4]. The SARS-Cov “S” glycoprotein comprises a conserved Receptor Binding Domain (RBD) which identifies receptors of host cell such as Ezrin, CD26, ACE2 and cyclophilins. It is 1200 amino acids long protein belongs to class1viral fusion proteins and involves in binding with cell’s receptor, pathogenesis and tissue tropism [5]. In the course of infection, the trimeric“S” protein is treated via proteases of host cell at the S1 or S2 cleavage site. Subsequent cleavage, also called it as priming, the protein is separated into two terminals: one is ‘S1’ ectodomain (N terminal) that identifies similar surface receptor of cell and other is ‘S2’ membrane anchored protein (C terminal) involved in entry of virus [6]. Therefore, by virtue of its key role, SARS-Cov ‘S’protein is considered as an appropriate objective for developing viral inhibitor. Inhibition of SARS-Cov‘S’ protein activity would block replication of virus. Since in humans, not at all any proteases with comparable cleavage specific are recognized, so inhibitors are improbable to be considered as toxic.
The invention of new drugs as therapeutic agents is a tedious and expensive process. Traditional methods can take about 12-14 years with lot of expenditure to bring a drug into market [7]. So as too overcome these challenges, multi disciplinary approaches are required in the process of drug discovery. In drug discovery processes, in-silico designing of drug is a form of computer based modeling which is very useful. This method offers advantage to deliver a new drug in fast and cost-effective manner. As of this date, the process of drug designing has been advanced with various bioinformatics tools which help in molecular docking analysis, protein- protein/ligand interaction, virtual screening and de-novo synthesis and in silico ADMET prediction.
From ancient time, medicinal plants are beneficial in the field of drug therapeutics as they are safer alternatives being utilized by humans for centuries [8]. Previously, many of the new drug formulations are derived from natural products. Our present study focuses on the in silico analysis of essential oil present in Eucalyptus plants. Various plant parts like flowers, leaves, roots and fruits have been used in various system of medicine for the past 2000 years to treat numerous diseases such as fever, skin infection, bleeding piles, asthma, cold, cough and inflammation. Hence, great attention has been paid to plant secondary metabolites as therapeutic medicines. Essential oils due to having antioxidant, antimicrobial and anti-viral bioactivities, immensely used in cosmetic, pharmaceutical industries. Essential oils are complex mixture of volatile elements such as flavonoids, alkaloids, aromatic compounds and terpenes. Eucalyptus essential oil has been empirically used as antimicrobial agents, but little is known about its antiviral potential [9]. We hypothesize that bioactives from essential oil have the capability to prevent infection of COVID-19. Therefore the research objective of the current study was in-silico analysis and comparative molecular docking studies pertain to bioactive molecules in relation with S-protein protein. The outcomes of the current study would provide researchers with prospects to recognize the accurate drug to combat COVID19. To further estimate the drug ability of this phytochemical, the present study report their ADMET profiles and potential biological activities using various in silico bioinformatics tools.