PMID- 35106293 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220430 IS - 2311-7710 (Electronic) IS - 2311-7710 (Linking) VI - 8 IP - 4 DP - 2021 Dec TI - Active site-specific quantum tunneling of hACE2 receptor to assess its complexing poses with selective bioactive compounds in co-suppressing SARS-CoV-2 influx and subsequent cardiac injury. PG - 540-556 LID - 10.5455/javar.2021.h544 [doi] AB - OBJECTIVE: This research aims to study the target specificity of selective bioactive compounds in complexing with the human angiotensin-converting enzyme (hACE2) receptor to impede the severe acute respiratory syndrome coronavirus 2 influx mechanism resulting in cardiac injury and depending on the receptor's active site properties and quantum tunneling. MATERIALS AND METHODS: A library of 120 phytochemical ligands was prepared, from which 5 were selected considering their absorption, distribution, metabolism, and excretion (ADMET) and quantitative structure-activity relationship (QSAR) profiles. The protein active sites and belonging quantum tunnels were defined to conduct supramolecular docking of the aforementioned ligands. The hydrogen bond formation and hydrophobic interactions between the ligand-receptor complexes were studied following the molecular docking steps. A comprehensive molecular dynamic simulation (MDS) was conducted for each of the ligand-receptor complexes to figure out the values - root mean square deviation (RMSD) (A), root mean square fluctuation (RMSF) (A), H-bonds, Calpha, solvent accessible surface area (SASA) (A(2)), molecular surface area (MolSA) (A(2)), Rg (nm), and polar surface area (PSA) (A). Finally, computational programming and algorithms were used to interpret the dynamic simulation outputs into their graphical quantitative forms. RESULTS: ADMET and QSAR profiles revealed that the most active candidates from the library to be used were apigenin, isovitexin, piperolactam A, and quercetin as test ligands, whereas serpentine as the control. Based on the binding affinities of supramolecular docking and the parameters of molecular dynamic simulation, the strength of the test ligands can be classified as isovitexin > quercetin > piperolactam A > apigenin when complexed with the hACE2 receptor. Surprisingly, serpentine showed lower affinity (-8.6 kcal/mol) than that of isovitexin (-9.9 kcal/mol) and quercetin (-8.9 kcal/mol). The MDS analysis revealed all ligands except isovitexin having a value lower than 2.5 A. All the test ligands exhibited acceptable fluctuation ranges of RMSD (A), RMSF (A), H-bonds, Calpha, SASA (A(2)), MolSA (A(2)), Rg (nm), and PSA (A) values. CONCLUSION: Considering each of the parameters of molecular optimization, docking, and dynamic simulation interventions, all of the test ligands can be suggested as potential targeted drugs in blocking the hACE2 receptor. CI - Copyright: (c) Journal of Advanced Veterinary and Animal Research. FAU - Nipun, Tanzina Sharmin AU - Nipun TS AD - Department of Pharmaceutical Chemistry, Faculty of Pharmacy, International Islamic University Malaysia, Kuantan, Malaysia. FAU - Ema, Tanzila Ismail AU - Ema TI AD - Department of Biochemistry and Microbiology, North South University, Dhaka, Bangladesh. FAU - Mia, Md Abdur Rashid AU - Mia MAR AD - Department of Pharmaceutical Technology, Faculty of Pharmacy, International Islamic University Malaysia, Kuantan, Malaysia. FAU - Hossen, Md Saddam AU - Hossen MS AD - Microbiology Major, Faculty of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, PR China. FAU - Arshe, Farzana Alam AU - Arshe FA AD - Department of Biochemistry and Microbiology, North South University, Dhaka, Bangladesh. FAU - Ahmed, Shahlaa Zernaz AU - Ahmed SZ AD - Department of Biochemistry and Microbiology, North South University, Dhaka, Bangladesh. FAU - Masud, Afsana AU - Masud A AD - Department of Biochemistry and Microbiology, North South University, Dhaka, Bangladesh. FAU - Taheya, Fatiha Faheem AU - Taheya FF AD - Department of Biochemistry and Microbiology, North South University, Dhaka, Bangladesh. FAU - Khan, Arysha Alif AU - Khan AA AD - Department of Biochemistry and Microbiology, North South University, Dhaka, Bangladesh. FAU - Haque, Fauzia AU - Haque F AD - Department of Biochemistry and Microbiology, North South University, Dhaka, Bangladesh. FAU - Azad, Salauddin Al AU - Azad SA AD - Fermentation Engineering Major, School of Biotechnology, Jiangnan University, Wuxi, PR China. FAU - Al Hasibuzzaman, Md AU - Al Hasibuzzaman M AD - School of Medicine, Ningbo University, Ningbo City, PR China. FAU - Tanbir, Mohammad AU - Tanbir M AD - Department of Biochemistry and Microbiology, North South University, Dhaka, Bangladesh. FAU - Anis, Samin AU - Anis S AD - Chattogram Maa-O-Shishu Hospital Medical College, University of Chittagong, Chattogram, Bangladesh. FAU - Akter, Sharmin AU - Akter S AD - Department of Genetics and Plant Breeding, Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur, Bangladesh. FAU - Mily, Sabrina Jahan AU - Mily SJ AD - Ministry of Health, People's Republic of Bangladesh, Dhaka, Bangladesh. FAU - Dey, Dipta AU - Dey D AD - Department of Biochemistry and Molecular Biology, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalgonj, Bangladesh. LA - eng PT - Journal Article DEP - 20210929 PL - Bangladesh TA - J Adv Vet Anim Res JT - Journal of advanced veterinary and animal research JID - 101647585 PMC - PMC8757663 OTO - NOTNLM OT - SARS-CoV-2 OT - cardiac injury OT - drug design OT - hACE2 receptor OT - molecular dynamic OT - quantum tunneling OT - simulation OT - supramolecular docking COIS- The authors have absolutely no conflicting interests with the others. EDAT- 2022/02/03 06:00 MHDA- 2022/02/03 06:01 PMCR- 2021/09/29 CRDT- 2022/02/02 05:35 PHST- 2021/08/18 00:00 [received] PHST- 2021/09/01 00:00 [revised] PHST- 2021/09/04 00:00 [accepted] PHST- 2022/02/02 05:35 [entrez] PHST- 2022/02/03 06:00 [pubmed] PHST- 2022/02/03 06:01 [medline] PHST- 2021/09/29 00:00 [pmc-release] AID - 10.5455/javar.2021.h544 [doi] PST - epublish SO - J Adv Vet Anim Res. 2021 Sep 29;8(4):540-556. doi: 10.5455/javar.2021.h544. eCollection 2021 Dec.