The novel corona virus disease identified in Wuhan City of China [1] spread across the earth as pandemic putting the whole world on high alert [2] [3] [4] [5] led to 823626 total cases and 40598 deaths all over the world till 01 April 2020 [6] . Available evidence indicates that this virus is transmitted through the respiratory droplets (such as coughing) and by fomites that can propagate through air at distances of 1 meter [7] [8] [9] and no evidence is available about its airborne transmission in the current study [10] which establishes the principle of maintaining the distance of more than 1 meter termed as 'social distancing'/'physical distancing' along with hand-hygiene for the prevention of COVID-19. A recent study based on the mathematical modeling conducted by Indian Council of Medical Research (ICMR) has suggested the proper quarantine and isolation as the preventive measures for stopping the outbreak of COVID-19 through community transmission [11] . It appears that in view of this, country-wide lock-down has been declared in India since the midnight of the 23 rd March, 2020 in continuation to pre-lock down action of evacuating the possible places expected for people's gathering as well as the social awareness drive already started from the very beginning of February, 2020 which we welcome.
Appreciable contribution in the development of diagnostics, therapeutics and vaccines for this novel corona virus has been indicated [11] and based on some clinical investigations, an anti-malarial drug namely chloroquine phosphate has been reported to be having a certain curative effect on the COVID-19 [12] . ICMR has also recommended an anti-malarial drug namely Hydroxy-chloroquine for those individuals which are asymptomatic healthcare workers involved in the care of suspected or confirmed cases of COVID-19 and asymptomatic household contacts of laboratory confirmed cases [13] . The possibility of high risk-factor associated with these suggested drugs has not been ruled out which projected it to be a trial measure. No specific therapy and medicine for the treatment of COVID-19 has ever been reported to the best of our knowledge which inspired us to think on the natural products relying on the concept of particle-antiparticle theory of Nature implying that if there is a novel corona virus then there must be its anti-virus material in the Nature itself and we have obtained motivating results in the present research carried out with the help of available computational facility at our home during lock-down period.
We have selected total eleven bioactive natural compounds embedded spontaneously in Anthocephalus Cadamba which has been reported to be a miraculous tree having crucial significance in Hindu Mythology containing the largest number of phytochemicals and secondary metabolites having pharmacological and biological properties, however, the solubility and solvent-effect to be the point of concern [14] . The four bio molecules contained in the leaves of the said tree namely 7-hydroxy-6-methoxy coumarian (C10H8O4), Methyl ester of chlorogenic acid (C17H20O9) , Pentyle Ester of Chlorogenic Acid (C21H28O9), D-Myo-Inositol (C7H14O6); 07 biomolecules contained in fruits of the said tree namely Oleanic Acid (C30H48O3), Ursolic Acid (C30H48O3), Vallesiachotamine (C21H22N2O3), Iso-Vallesiachotamine (C21H22N2O3), Cadambine (C27H32N2O10), Vincosamide-N-Oxide (C26H31N2O9), Isodihydroamino-cadambine (C26H33N3O7) already reported to be isolated and characterized in Central Drug Research Institute, Lucknow, India [15] [16] and the electronic properties of the few of them have already been studied by us computationally [17] [18] [19] [20] [21] ; were screened as ligands to interact with the targeted SARS-COV-2 protease. The first two of the aforsaid compounds responded negatively but rest nine compounds exhibited the positive results which have been presented in this paper. We expect that the present study will offer a new dimension in developing the drug/vaccine for the COVID-19.
The In silico optimized ligand-structure of the aforementioned eleven bioactive natural compounds were obtained as per reported approach of density functional theory at B3LYP/631+G (d, p) level [22] [23] implemented through Gaussian 09 program-package [24] . We have used main protease of SARS-COV-2 retrieved from the RCSB protein data bank having PDB ID: 6Y84 [25] and PDB ID: 6LU7 [26] as potential target protein for the binding of these ligands obtained using molecular docking approach implemented through Autodock 4.2 program package [27] [28] [29] . The binding of these natural bioactive ligands with the PDB ID: 6CRV which is SARS Spike Glycoprotein for corona virus SARS-COV emerged in 2002 as a highly transmissible [30] has also been obtained with the help of same docking approach in order to investigate the consistency of the performance of these compounds with the class of viral protein. The binding of these compounds with the PDB ID: 6VXX which is the SARS-COV-2 spike glycoprotein for COVID- 19 [31] has also been examined to illustrate the potential of these compounds to deactivate this novel corona virus at the receptor end.
The In silico optimized molecular structure of 09 bioactive natural compounds modeled using DFT-B3LY/6- The significantly negative value of the final free energy of binding obtained through the molecular docking of these compounds with the SARS-COV-2 protease reveals that these molecules may be explored as potential inhibitor against COVID-19. Since these compounds are naturally occurring, hence they do not cost for their synthesis and bears less or nil side-effect which enables them to be explored as user-friendly drug. The solubility and the effect of the solvent which are usually associated with the phytochrmicals may be the point of attention while using these compounds as drug candidate. The other chemical structure may also be derived from these bioactive natural compounds to further design potential drug agent for COVID-19. Similar types of significant binding affinity have been obtained in all the SARS-COV-2 spike glycoproteinligand (studied compounds) interactions whose results are available on demand but not depicted due to space limitations.
We have carried out a schematic In Silico investigation applying density functional theory and molecular docking approach on the nine naturally occurring bioactive compounds listed in figure 1 spontaneously found in the leaves and fruits of Anthocephalus cadamba. On the basis of the binding affinity, we have found these compounds as potential inhibitors against the COVID-19 having final free energy of binding in the order of molecule 1>2>3>4>5>6>7>8>9. These molecules have also emerged as potential inhibitors against the SARS-COV-2 spike glycoprotein for COVID-19 in our investigation. These compounds may be explored as drug candidate and their molecular structure may be exploited to develop a vaccine for COVID-19. In-vivo study is invited on these compounds for developing user friendly drug for COVID-19. The further study on derived structures of these compounds is going on in our laboratory.