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Point-specific interactions of isovitexin with the neighboring amino acid residues of the hACE2 receptor as a targeted therapeutic agent in suppressing the SARS-CoV-2 influx mechanism
2022
Nourin Ferdausi (Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh) | Samarth Islam (Department of Biochemistry and Microbiology, North South University, Dhaka, Bangladesh) | Fahmida Hoque Rimti (Bachelor of Medicine and Surgery, Chittagong Medical College, Chittagong, Bangladesh) | Syeda Tasnim Quayum (Department of Biochemistry and Microbiology, North South University, Dhaka, Bangladesh) | Efat Muhammad Arshad (Department of Biochemistry and Microbiology, North South University, Dhaka, Bangladesh) | Aashian Ibnat (Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh) | Tamnia Islam (Wolfson Institute for Biomedical Research, Division of Medicine, University College London, London, United Kingdom. & Immunoinformatics and Vaccinomics Research Unit, RPG Interface Lab, Jashore, Bangladesh) | Adittya Arefin (Wolfson Institute for Biomedical Research, Division of Medicine, University College London, London, United Kingdom. & Immunoinformatics and Vaccinomics Research Unit, RPG Interface Lab, Jashore, Bangladesh) | Tanzila Ismail Ema (Department of Biochemistry and Microbiology, North South University, Dhaka, Bangladesh. & Immunoinformatics and Vaccinomics Research Unit, RPG Interface Lab, Jashore, Bangladesh) | Partha Biswas (Department of Genetic Engineering and Biotechnology, Jashore University of Science and Technology, Jashore, Bangladesh. & Immunoinformatics and Vaccinomics Research Unit, RPG Interface Lab, Jashore, Bangladesh) | Dipta Dey (Department of Biochemistry and Molecular Biology, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj,Bangladesh. & Immunoinformatics and Vaccinomics Research Unit, RPG Interface Lab, Jashore, Bangladesh) | Salauddin Al Azad (Fermentation Engineering Major, School of Biotechnology, Jiangnan University, Wuxi, PR China. & Immunoinformatics and Vaccinomics Research Unit, RPG Interface Lab, Jashore, Bangladesh.)
Objective: Despite the development of several vaccines against severe acute respiratory syndrome coronavirus-2, the need for an additional prophylactic agent is evident. In recent in silico studies, isovitexin exhibited a higher binding affinity against the human angiotensin converting-enzyme 2 (hACE2) receptor than existing antiviral drugs. The research aimed to find out the point specificity of isovitexin for the hACE2 receptor and to assess its therapeutic potential, depending on the stability of the isovitexin–hACE2 complex. Materials and Methods: The pharmacokinetic profile of isovitexin was analyzed. The crystal structure of the hACE2 receptor and the ligand isovitexin were docked to form a ligand-protein complex following molecular optimization. To determine the isovitexin–hACE2 complex stability, their binding affinity, hydrogen bonding, and hydrophobic interactions were studied. Lastly, the root mean square deviation (RMSD), root mean square fluctuation, solvent accessible surface area, molecular surface area, radius of gyration (Rg), polar surface area, and principal component analysis values were found by simulating the complex with molecular dynamic (MD). Results: The predicted Lethal dose50 for isovitexin was 2.56 mol/kg, with an acceptable maximum tolerated dose and no hepatotoxicity or AMES toxicity. Interactions with the amino acid residues Thr371, Asp367, Glu406, Pro346, His345, Phe274, Tyr515, Glu375, Thr347, Glu402, and His374 of the hACE2 protein were required for the high binding affinity and specificity of isovitexin. Based on what was learned from the MD simulation, the hACE2 receptor-blocking properties of isovi¬texin were looked at. Conclusions: Isovitexin is a phytochemical with a reasonable bioactivity and safety profile for use in humans, and it can potentially be used as a hACE2-specific therapeutic to inhibit COVID-19 infection. [J Adv Vet Anim Res 2022; 9(2.000): 230-240]
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