A new strain of a novel infectious disease affecting millions of people, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently been declared as a pandemic by the World Health Organization (WHO). Currently, several clinical trials are underway to identify specific drugs for the treatment of this novel virus. The inhibition of the SARS-CoV-2 main protease is necessary for the blockage of the viral replication. Here, in this study, we have utilized a blind molecular docking approach to identify the possible inhibitors of the SARS-CoV-2 main protease, by screening a total of 33 molecules which includes natural products, anti-virals, anti-fungals, anti-nematodes and anti-protozoals. All the studied molecules could bind to the active site of the SARS-CoV-2 protease (PDB: 6Y84), out of which rutin (a natural compound) has the highest inhibitor efficiency among the 33 molecules studied, followed by ritonavir (control drug), emetine (anti-protozoal), hesperidin (a natural compound), lopinavir (control drug) and indinavir (anti-viral drug). All the molecules, studied out here could bind near the crucial catalytic residues, HIS41 and CYS145 of the main protease, and the molecules were surrounded by other active site residues like MET49, GLY143, HIS163, HIS164, GLU166, PRO168, and GLN189. As this study is based on molecular docking, hence being particular about the results obtained, requires extensive wet-lab experimentation and clinical trials under in vitro as well as in vivo conditions. ARTICLE HISTORY
The binding of two bio-active flavonoids, quercetin and rutin, with bovine hemoglobin (BHb) was investigated by multi-spectroscopic and computational (molecular docking and molecular dynamics simulation) studies. The two flavonoids were found to quench the intrinsic fluorescence of BHb through a static quenching mechanism. The binding constants at 288 K were observed to be (14.023 ± 0.73) × 104 M-1 and (7.848 ± 0.20) × 104 M-1, respectively for quercetin and rutin binding with BHb. Both rutin and quercetin were observed to increase the polarity around the Trp residues of BHb as indicated by synchronous and 3D spectral studies. No significant alterations in the secondary structural components of the protein were caused during the binding of the flavonoids as studied by CD and FTIR studies. The negative molar Gibbs free energies indicated the spontaneity of the interaction processes while the binding processes were characterized by a negative enthalpy change (ΔH) and a positive entropy change (ΔS). The possibility of energy transfer from the donor (BHb) to the acceptor molecules (flavonoids) was indicated by the FRET studies. According to the fluorescence studies, the flavonoids interact near to the β2-Trp37 residue of BHb. Excellent correlations with the experimental studies were observed from the molecular docking and molecular dynamics (MD) simulation studies. Further investigations established that these flavonoids are efficient in the inhibition of glucose mediated glycation of BHb.
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