INTRODUCTION:

Covid-19 or corona virus is an infectious respiratory disease¹. Covid-19 caused by (SARS CoV-2) severe acute respiratory syndrome corona virus^2,3,. It began to spread over the world in late December. It first appeared in China, in Wuhan city. And it is currently affecting almost every country on the planet^4,5. It has been declared a pandemic disease by the WHO (World Health Organization)⁵. This pandemic disease related deaths crossed near about 6.3 million worldwide till the 24 May 2022. Fever, dry cough, weariness, chills, body acne, and breathing problems, as well as short breath problems, chest pain, are all symptoms of Covid 19^4,6. Basically, sars-cov-2 interacts with lung epithelial cells and triggers an immunological response and cytokinin storm, resulting in respiratory failure, which is the most prevalent cause of death in the Covid -19 pandemic. SARS-CoV-2 is an enveloped single- stranded positive sense RNA virus and it has ability to change its structure according to the climatic conditions^7,8,9.

In the midst of a pandemic, one of the tragedies is that there are no particular antiviral medications available to treat covid-19^10,11.. All drugs in market are supplied only for supportive purpose but Covid-19 vaccines, such as covishield, covaxin, Pfizer, and sputnik, are currently being developed.^12,13,14

Various receptor protein of SARS CoV-2 was structure out. For performing the study we select two recently structured out SARS CoV-2 receptor protein such as SARS CoV-2 receptor in complexed with antibody ION-300(PDB ID-7BNV) with DOI: 10.2210/pdb7BNV/pdb and expression system is homo-sapiens and second one is SARS CoV-2 receptor spike protein complexed with neutralizing antibody CT-P59(PDB ID-7CM4) with DOI: 10.2210/pdb7CM4/pdb which is downloaded from protein data bank(https://www.rcsb.org)

For this investigation, we select marine sponges derived compound such as Vidarabine Avarol and Mycalamide A and Phycocyanobilin which is algae metabolite. Vidarabine is a purine nucleoside isolated from Tethya crypta, a Caribbean sponge. Vidarabine is an antiviral that can be used to treat herpes, poxviruses, rhabdoviruses, hepadnaviruses, and certain RNA tumour viruses. Avarol is a sesquiterpenoid hydroquinone isolated from the Dysidea avara (Dysideidae) sponge that has anti-psoriatic and antiviral properties. Mycalamide A, is marine natural compound isolated from sponges from a New Zealand sponge of the genus Mycale. it is known as a protein synthesis inhibitor with potent antitumor activity. Phycocyanobilin is a blue phycobilin, a tetrapyrrole chromophore found in cyanobacteria, red algae, glaucophytes, and some cryptomonad chloroplasts. Its primary purpose is to aid in the selective elimination of atherosclerotic plaques or cancer cells. We select these marine bioactive compounds against SARS CoV-2 receptor protein complexed with antibody to check its binding affinity to the receptor by using Schrodinger docking software.^15-22.

MATERIAL AND METHOD:

Data source:

In order to get two-dimensional configuration of marine bioactive compound a Pub-Chem database (https://pubchem.ncbi.nlm.nih.gov) was used. A protein database of PDB (https://www.rcsb.org) was used to achieve whole configuration of SARS CoV-2 receptor protein complexed with antibody.

Ligand preparation:

The following marine bioactive compound molecules were taken from the database Pub-Chem(https://pubchem.ncbi.nlm.nih.gov) prepare ligand by using Schrodinger software. The selected compound is Vidarabine (CID ID:21704), Avarol (CID ID:72185), Phycocyanobilin (CID ID:365902), Mycalamide A (CID ID:10345974)

Figure 1: Ligand mole of Marine bioactive compound a) Phycocyanobilin b) Vidarabine c) Mycalamide A d) Avarol

Protein preparation:

The SARS CoV-2 receptor spike protein complexed with antibody ION-300 (PDB ID-7BNV) and SARS CoV-2 receptor protein complexed with antibody CT-P59 were obtained from the RCSB PDB (protein data bank) (PDB ID-7CM4). Protein preparation is done with Schrodinger software, which optimizes and minimizes protein.

Table 1: PDB ID of SARS CoV-2 receptor spike protein complex with antibody

Sr. No	Receptor Name	PDB ID
1	SARS CoV-2 receptor complexed with antibody ION-300	7BNV
2	SARS CoV-2 Spike protein receptor complexed with neutralizing antibody CT-P59	7CM4

Figure 2: Protein preparation of 7CM4 and 7BNV

Site-map generation:

After protein preparation for detection of active binding site of protein molecules next task is to perform site-map generation. Software generates different binding sites in protein molecule with different D score value from that we selected site which having more D score value. That means it shows the binding site which having high D score shows good binding site for the ligand molecule.

Figure 3: Site map of protein 1- 7CM4 and 2- 7BNV

RESULT AND DISCUSSION:

This study examines the binding mode of SARS CoV-2 recently developed protein in complex with antibody using computer docking analysis by using Schrödinger software (maestro v 10.2). We select two protein complexes with antibody which having PDB ID are 7BNV, 7CM4.Four marine bioactive compound have been docked and evaluate according to targeted protein all selected marine bioactive compound significantly interacts with receptor protein of Covid 19 virus. For Covid 19 restraint compound with the glide score which is above -3 is consider to be good. That means it shows good binding with receptor protein. Table 2 shows highest glide score of compounds against SARS CoV-2 is i.e., -6.18, and the lowest -2.72.

The highest glide score which is – 6.18 which is for Phycocyanobilin against SARS Cov-2 receptor in complex antibody ION-300 (7BNV) that means it shows higher binding affinity toward the receptor and Mycalamide A which having -3.80 glide score which shows poor or low binding affinity toward this receptor as compared to Phycocyanobilin. similarly for another SARS CoV-2 Spike protein receptor complexed with neutralizing antibody CT-P59 Vidarabine shows good binding affinity toward this receptor with a glide score -5.32.and Mycalamide A which having glide score -2.72 shows poor binding affinity toward receptor. Here are images of docking of ligand with the two different receptors with antibody.

Figure 4: Molecular docking of 7BNV with 1.Phycocyanobilin 2.Avarol 3.Vidarabine 4. Mycalamide A

In figure 4, Part-1 shows molecular association with SARS CoV-2 receptor protein in complex with antibody ION-300. It intereact with Phycocyanobilin by forming 3 hydrogen bond namely Gly H: 42 (2.05 A⁰), Glu H: 162 (1.73 A⁰) AlaH: 182 (1.80 A⁰) . Part - 2 shows intereaction with the receptor by forming the one hydrogen bond (sidechain) with Glu l: 168 (2.69 A⁰). Part – 3 shows intereaction by forming the 5 hydrogen bond are as Gln H : 39 (2.20 A⁰), Met h: 40 (2.70 A⁰), Gly H: 42 (2.09 A⁰), Glu L: 168 (1.64 A⁰),Glu L: 168 (1.93 A⁰). Part – 4 show intereaction by forming the 3 hydrogen bond are as Lys H: 43 (2.68 A⁰), Glu L: 168 (1.58 A⁰), Glu L: 168 (1.99 A⁰).

Figure 5: Molecular docking of 7CM4 with 1.Phycocyanobilin 2.Avarol 3.Vidarabine 4.Mycalamide A

In figure 5, Part-1 shows molecular association with SARS CoV-2 Spike protein receptor complexed with neutralizing antibody CT-P59. It intereact with Phycocyanobilin by forming 4 hydrogen bond namely Lys H: 45 ( 1.75 A⁰), Gly H: 44 (2.73 A⁰) Pro H: 43 (2.07 A⁰) Lys L: 167 (2.49 A⁰) one salt bridge (3.68 A⁰) one pi-cation (6.30 A⁰) . Part -2 shows intereaction with the receptor by forming the 2 hydrogen bond with Pro H: 42 (2.21 A⁰) and Asp L: 86 (1.87 A⁰). Part-3 shows intereaction by forming the 4 hydrogen bond are as Asp L: 86 (1.76 A⁰), Glu H: 84 (1.92 A⁰), Glu L: 106 (2.31 A⁰), Glu L: 106 (1.65 A⁰) and one pi-cation with lys l: 167 (3.29). Part-4 show intereaction by forming the 2 hydrogen bond are as ASP L:86 (1.82 A⁰), ASP L:86 (2.21 A⁰) .Table no 2 show the glide score of marine bioactive compound which is calculate by using shrodinger docking software.

Table 2: Glide score of marine bioactive compound.

Sr. No	Compound Name	CID ID	PDB ID 7BNV	PDB ID 7CM4
Sr. No	Compound Name	CID ID	Glide score	Glide score
1	Phycocyanobilin	365902	-6.18	-4.48
2	Avarol	72185	-4.75	-3.85
3	Vidarabine	21704	-5.22	-5.32
4	Mycalamide A	10345974	-3.80	-2.72

CONCLUSION:

Our current molecular docking study indicate that the marine bioactive compound i.e., Vidarabine, Avarol, Phycocyanobilin, Mycalamide A are good ligand molecule for significantly binds with SARS CoV-2 receptor in complex with antibody (ION-300, CT-P59) work by interacting with it these marine bioactive compound used to produce safe and effective drug and also these compound help in lead detection in modern method and identified lead compound will then tested in vitro and in vivo to see how successful they are against SARS CoV-2(Covid –19).

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Received on 15.06.2022 Modified on 12.09.2022

Research J. Pharm. and Tech 2023; 16(8):3805-3808.

DOI: 10.52711/0974-360X.2023.00628