Molecular docking results were identified basis on the ideal interacted ligands were scrutinized based on the greatest ligand binding poses were identified using the low binding energy, high docking score and the number of H-bonding, hydrophobic interactions at receptor site. In the Table.1, 2, 3, 4 represents the docking score, Hydrogen bond distance and interacting atoms. All the compounds were found to be buried. Molecular docking interactions with receptor [Crystal Structure of COVID-19 main protease in complex with Z18197050 (5r80)] and ligand (Stranded drugs) was represented in table (1 to 4). NH (amino groups) atom of Doravirine, Emtricitabine, Raltegravir and Tenofavir Disproxil was found to strongly binds to COVID-19 protease complex at THR25-OG1 (H-bond Distance Ao=2.55), THR190-O (Ao= 2.96), GLU166-O (Ao =2.78) and GLU166-O (Ao =2.25) respectively. Among these Doravirine and Tenofavir Disproxil has strong binding affinity with COVID 19 protease complex with docking score is -86.864 and -85.375 Kcal/mol respectively (table 1 and Fig 1). Another receptor of Nsp9 replicase protein of COVID-19 (6W4B)] and ligand (Stranded drugs) interaction showed that nitrogen group (NH) of stranded drugs with receptor molecule 6W4B with less hydrogen bond [Atazanavir (GLN50-NE2=2.74 and MET1-O=2.98), Doravirine(THR35-OD1=2.86), Entravirine (SER6-O=2.61 and VAL8-O=2.84), Hydroxy chloroquine (Thr68-OG1=2.81), Raltegravir (ARG56=2.74 and ASP27OD1=2.77), Tenofavir Disproxil(PRO58-O=2.61) and Zidovudine(PRO58-O=2.59)] respectively(table 2 and Fig 2).
NH atom of selected ligands binds effectively to the active site of COVID19 protease complex (6Y84) at different amino acids positions with less hydrogen bond distance [Doravirine (PHE185-O= 2.97, PHE185-O= 2.98, ASP187-O= 2.92), Emtricitabine (SER144-OG=2.91, CYS145-N=2.90 ), Etravirine (SER144-OG=2.63), Zidovudine (PHE140-O=2.66, GLY143-N=2.73 and CYS145-N=2.90)] (table 3 and Fig 3).
The receptor molecule of Coronavirus attachment to sialic acid receptors- Apo-HCoV-OC43 (6OHW)] high affinity binding to NH atom of drugs such Doravirine(ASN133-ND2=2.95), Emtricitabine (SER196-OG=2.98; GLN165-OE1= 2.60), Entravirine(GLN165-OE1=2.57), Raltegravir(GLY193-N=2.74; THR192-N=2.66), Tenofavir Disproxil (VAL194-O=2.64; VAL194-O=2.85). (Table 4 and Fig 4). Hydrogen molecule present on the Tipranavir and Zidovudine also binds to the 60HW protein molecule at ASN167-ND2 and ASP191-OD1 with less hydrogen bond distance 2.98 and 2.66 respectively. Lesser the hydrogen bond distance between the protein molecules and ligands of stranded drugs indicate that higher the affinity, stability of bonding is more and specific. Hence in these molecular docking studies are showing that the i.e., Atazanavir, Doravirine, Emtricitabine, Etravirine, Hydroxychloroquine, Raltegravir, Tenofavir Disoproxil, Tipranavir, Zidovudine are interacting with corona virus (COVID 19) receptor or protein complexes. These drugs might be better useful for the treatment of SARS-COV19 disease.
Genemania: It is a literature-based web interface tool for prediction genes interaction with other molecules and protein -protein interaction i.e. is protein data base and gene data base. Several studies are suggested that after COVID 19 viral infection ACE2 and TMPRSS2 proteins are upregulated, leads to the acqute respiratory syndrome. Genemania results are suggested that ACE2 physically interacts with angiotensin (AGT), Catalase (CAT), inositol-3-phosphate synthase 1 (ISYNA1), angio associated migratory cell protein (AAMP) and ghrelin and obestatin prepropeptide (GHRL), Co-expression with CAT, annexin A13 (ANXA13), solute carrier family 10 member 2 (SLC10A2), glycerol kinase (GK), fyn related Src family tyrosine kinase (FRK), GHRL, trehalase (TREH), glutathione S-transferase alpha 3(GSTA3), transmembrane protein 27 (TMEM27), angio associated migratory cell protein (AAMP), cadherin related family member 2(CDHR2), hook microtubule tethering protein 1 (HOOK1)…. etc. Co-localize with solute carrier family 12 member 6(SLC12A6), GK, fyn related Src family tyrosine kinase (FRK), HOOK1…etc, Shared protein-protein domains other molecules like ACE, TMEM27, …etc. still pathway of ACE2 was not understood (Fig 5). TMPRSS2 protein co-express with kallikrein related peptidase 2, 3 and 4 (KLK2, KLK3 and KLK4), androgen receptor (AR), solute carrier family 37 member 1 (SLC37A1), acyl carrier protein (ACP), solute carrier family 45 member 3(SLC45A3), solute carrier family 6 member 4 (SLCA4), …like molecules. It is co-localized with KLK3, KLK2, KLK4, AR, SLC44A4, phosphodiesterase 9A (PDE9A), SLC37A1, etc. TMPRSS2, KLK2, KLK3, AR, lysine demethylase 3A (KDM3A), PDE9A are in same pathway. TMPRSS2 is share protein-protein domains with KLK4, KLK2 and KLK3 (Fig 6). Genemania does show any interactions between the ACE2 and TMPRSS2 proteins. The common protein molecule found to interact with the ACE2 and TMPRSS2 are solute carrier family proteins. Understanding of these protein and gene network will help to design the drugs against COVID 19 virus.