In- Silico Studies on Selected Active Constituents of Corbichonia decumbens Against Allergic Bronchopulmonary Aspergillosis

Herbs have been employed in the treatment of various diseases and other medicinal purposes for a long time and they’ve been the zest of our life. Corbichonia decumbens an erect, short-lived succulent herb is found to possess zenith medicinal properties. At a first, the in-silico activity of the plant has been determined to carry out a modification in the Surfactant Protein-D (SP-D) which plays a pivotal role in defense against the Allergic Bronchopulmonary Aspergillosis (ABPA). The SP-D protein has been modified using in-silico tools thus making it more robust in containing ABPA. The protein SP-D when combined with the plant compound 1-methyl-3,5dinitro-1,2,4-triazole had binding energy of -6.98 and interactions with active site residue ASN-236, LYS-246, GLU-232, PHE-234 and, GLN-236. Being one of the first in-silico works carried out in this plant species it aims to provide a substantial base for future works and unwrap the potential of this herb in all aspects of medicinal plant science.


Introduction
The use of plants in the preparation of medicine and ethnobotanical studies is being practiced since time immemorial. The term medicinal plants have been in force since ancient times and these medicinal plants are used in the preparation of traditional medicines. In India, the use of herbs is mentioned in Vedic scriptures. In India, it is believed that the taxonomical rank of classification & naming of plants in the Sanskrit language is much older than that of Latin and Greek languages and the study dates back to the Vedic period from 2500 BC to 600 BC (Balkrishna, Mishra and Srivastava, 2019). Parts of plants such as fruits, flowers, seed, stem, bark, leaf, stigma, or a root can be classified as herbs nowadays. At first, the 'herb' referred to non-woody plants, as well as those that came from trees and shrubs. The medicinal plants find a varied application in the manufacture of food, flavonoids, medicine, perfumes and also utilized for sacred activities (NHP, 2016). Corbichonia decumbens belonging to the family of Lophiocarpaceae is an erect, prostrate-ascending annual or short-lived perennial succulent herb up to 50cm. in height, sometimes with woody rootstock found in the pavements in and around the Annur region of Coimbatore. This potential herb can be well utilized as an effective source of the drug for various diseases as they have an intrinsic capacity to synthesize aromatic substances such as phenols, and their derivatives (Geissman, 1963). These secondary metabolites tend to exhibit their therapeutic tendencies. These  (Wright, 2005). SP-D is believed to play a vital role in innate immunity in the lungs by binding through its multiple C-type lectin domains to carbohydrate structures present on a range of viruses, bacteria, yeasts, and fungi (Reid, 1998). Bio-informatics tools helped in the successful visualization of the target-compound interactions, as drug discovery programs primarily start with the identifications of suitable drug targets, which are biomolecules such as proteins, enzymes, and ion-channels (Terstappen & Reggiani, 2001). The initial steps of drug validation can be obtained through insilico and animal models, but the outcome can only be obtained through human clinical trials. The study aims to bring out the efficient use of SP-D with the plant compound of C. decumbens against ABPA disease and to emphasize the significance of C. decumbens as a potential herb as it is one of the first in-silico works in this plant to date.

Materials and methods
The plant compounds which were already obtained from GC-MS analysis (Saranya & Arunprasath, 2019) were retrieved from online databases such as;

PDB, PubChem & Pass Online
The 3D protein structure for the Surfactant Protein-D (SP-D) is recovered from the Protein Data Bank database (PDB ID: 4M18). Dynamic web page region was anticipated utilizing LigSite online apparatus. The PASS ONLINE predicts 4130 types of biological activities, for which the difference between probabilities will be active (Pa) and probabilities will be inactive (Pi) was calculated. The Pa-Pi values for activities randomly selected from the total list of predicted biological activities will be used as independent regression variables are perused.
Lipinski rule of 5 helps in distinguishing between drug-like and non-drug-like molecules (Yongqiang Zhang et al., 2020). It predicts a high probability of success or failure due to drug-likeness for molecules complying with 2 or more of the following rules.

Results
The retrieved compounds were analyzed for PASS prediction (Table 1) from which the activity of compounds was confirmed. Further, the compounds were subjected to Absorption, Distribution, Metabolism, and Excretion properties, and the results were tabulated ( Table 2). The compounds weren't found to violate Lipinski's rule of five. First-hand knowledge of this information is much necessary before drug discovery as it has a great impact on the cost, labor, and time duration. Lipinski's rule of five is also called Pfizer's rule of five or the rule of thumb to evaluate drug-likeness to indicate the following properties like molecular weight, octanol/water partition coefficient, hydrogen bond donor, and acceptor. The results of docking studies were recorded in (Table 3) and it revealed the compound 1-methyl-3, 5-dinitro-1, 2,4-triazole from Corbichonia decumbens with SP-D shows binding energy of -6.98 (Fig 1). The interactions were observed using Pymol.

Discussion
The disease Allergic Bronchopulmonary Aspergillosis (ABPA), caused by the fungi Aspergillus fumigatus is a hypersensitivity lung disease which is rarely found in 10% of persons having cystic fibrosis (Keown et al., 2019).
A positive response to this disease was created using the in-silico tools which succored in the successful docking analysis. The ABPA is more ubiquitous in patients who have been diagnosed of asthma (David et al., 1999). The compounds displayed an acceptable binding energy with surfactant protein D, as these are lung surfactant related hydrophilic proteins that have been implicated in surfactant homeostasis and pulmonary innate immunity (U.

CONCLUSION
The chemical compound 1-methyl-3,5-dinitro-1,2,4-triazole had a much significant binding energy of -6.98 and interactions with active site residue ASN-236, LYS-246, GLU-232, PHE-234 and, GLN-236. A wide variety of compounds were selected for this study but after the scrutinizing only handful of standard compounds were considered. The above plant compounds could be explored more for ABPA & the identification of an efficient and potential drug molecule by enhancing the activity of SP-D protein and thus making it a super protein by combining this compound.