PMID- 34909066 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230210 IS - 1878-5379 (Electronic) IS - 1878-5352 (Print) IS - 1878-5352 (Linking) VI - 15 IP - 1 DP - 2022 Jan TI - QSAR based virtual screening derived identification of a novel hit as a SARS CoV-229E 3CL(pro) Inhibitor: GA-MLR QSAR modeling supported by molecular Docking, molecular dynamics simulation and MMGBSA calculation approaches. PG - 103499 LID - 10.1016/j.arabjc.2021.103499 [doi] AB - Congruous coronavirus drug targets and analogous lead molecules must be identified as quickly as possible to produce antiviral therapeutics against human coronavirus (HCoV SARS 3CLpro) infections. In the present communication, we bear recognized a HIT candidate for HCoV SARS 3CLpro inhibition. Four Parametric GA-MLR primarily based QSAR model (R2:0.84, R2adj:0.82, Q2loo: 0.78) was once promoted using a dataset over 37 structurally diverse molecules along QSAR based virtual screening (QSAR-VS), molecular docking (MD) then molecular dynamic simulation (MDS) analysis and MMGBSA calculations. The QSAR-based virtual screening was utilized to find novel lead molecules from an in-house database of 100 molecules. The QSAR-vS successfully offered a hit molecule with an improved (P)EC(50) value from 5.88 to 6.08. The benzene ring, phenyl ring, amide oxygen and nitrogen, and other important pharmacophoric sites are revealed via MD and MDS studies. Ile164, Pro188, Leu190, Thr25, His41, Asn46, Thr47, Ser49, Asn189, Gln191, Thr47, and Asn141 are among the key amino acid residues in the S1 and S2 pocket. A stable complex of a lead molecule with the HCoV SARS 3CLpro was discovered using MDS. MM-GBSA calculations resulted from MD simulation results well supported with the binding energies calculated from the docking results. The results of this study can be exploited to develop a novel antiviral target, such as an HCoV SARS 3CLpro Inhibitor. CI - (c) 2021 The Author(s). FAU - Jawarkar, R D AU - Jawarkar RD AD - Department of Medicinal Chemistry, Dr. Rajendra Gode Institute of Pharmacy, University-Mardi Road, Amravati, Maharashtra, 444603, India. FAU - Bakal, Ravindrakumar L AU - Bakal RL AD - Department of Medicinal Chemistry, Dr. Rajendra Gode Institute of Pharmacy, University-Mardi Road, Amravati, Maharashtra, 444603, India. FAU - Zaki, Magdi E A AU - Zaki MEA AD - Department of Chemistry, Faculty of Science, Al-Imam Mohammad Ibn Saud Islamic university, Riyadh 13318, Saudi Arabia. FAU - Al-Hussain, Sami AU - Al-Hussain S AD - Department of Chemistry, Faculty of Science, Al-Imam Mohammad Ibn Saud Islamic university, Riyadh 13318, Saudi Arabia. FAU - Ghosh, Arabinda AU - Ghosh A AD - Microbiology Division, Department of Botany, Gauhati University, Guwahati, Assam 781014, India. FAU - Gandhi, Ajaykumar AU - Gandhi A AD - Department of Chemistry, Government College of Arts and Science, Aurangabad, Maharashtra 431 004, India. FAU - Mukerjee, Nobendu AU - Mukerjee N AD - Department of Microbiology; Ramakrishna Mission Vivekananda Centenary College, Akhil Mukherjee Rd, Chowdhary Para, Rahara, Khardaha, Kolkata, West Bengal 700118, India. FAU - Samad, Abdul AU - Samad A AD - Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tishk International University, Erbil, Kurdistan Region, Iraq. FAU - Masand, Vijay H AU - Masand VH AD - Department of Chemistry, Vidyabharti Mahavidyalaya, Camp Road, Amravati Maharashtra, India. FAU - Lewaa, Israa AU - Lewaa I AD - Department of Business Administration, Faculty of Business Administration, Economics & Political Science, The British University in Egypt (BUE), Cairo, Egypt. LA - eng PT - Journal Article DEP - 20211019 PL - Saudi Arabia TA - Arab J Chem JT - Arabian journal of chemistry JID - 101547033 PMC - PMC8524701 OTO - NOTNLM OT - 3CLpro, 3C like Protease OT - FDA, Food and Drug Administration OT - GA-MLR OT - GA-MLR, Genetic Algorithm Multilinear Regression OT - HCoV SARS 3CLpro OT - HCoV-HKU1, Human coronavirus HKU1 OT - HCoV-NL63, Human coronavirus NL63 OT - HCoVs, human coronaviruses OT - Lead OT - MD, Molecular Docking OT - MDS, molecular dynamic simulation OT - MERS, Middle East Respiratory Syndrome OT - MMGBSA calculations OT - MMGBSA, Molecular Mechanics Generalized Born and Surface Area OT - Molecular docking and MD simulation OT - OECD, Organization for Economic Corporation and Development OT - QSAR based virtual screening OT - QSAR, Quantitative Structure Activity Relationship OT - RNA, Ribo-nucleic acid OT - SARS, severe acute respiratory sign OT - VS, Virtual Screening COIS- The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2021/12/16 06:00 MHDA- 2021/12/16 06:01 PMCR- 2021/10/19 CRDT- 2021/12/15 12:28 PHST- 2021/07/31 00:00 [received] PHST- 2021/10/10 00:00 [accepted] PHST- 2021/12/15 12:28 [entrez] PHST- 2021/12/16 06:00 [pubmed] PHST- 2021/12/16 06:01 [medline] PHST- 2021/10/19 00:00 [pmc-release] AID - S1878-5352(21)00514-1 [pii] AID - 103499 [pii] AID - 10.1016/j.arabjc.2021.103499 [doi] PST - ppublish SO - Arab J Chem. 2022 Jan;15(1):103499. doi: 10.1016/j.arabjc.2021.103499. Epub 2021 Oct 19.