PMID- 35639226 OWN - NLM STAT- MEDLINE DCOM- 20230510 LR - 20230513 IS - 1573-501X (Electronic) IS - 1381-1991 (Print) IS - 1381-1991 (Linking) VI - 27 IP - 2 DP - 2023 Apr TI - Amentoflavone derivatives significantly act towards the main protease (3CL(PRO)/M(PRO)) of SARS-CoV-2: in silico admet profiling, molecular docking, molecular dynamics simulation, network pharmacology. PG - 857-871 LID - 10.1007/s11030-022-10459-9 [doi] AB - SARS-CoV-2 is the foremost culprit of the novel coronavirus disease 2019 (nCoV-19 and/or simply COVID-19) and poses a threat to the continued life of humans on the planet and create pandemic issue globally. The 3-chymotrypsin-like protease (M(PRO) or 3CL(PRO)) is the crucial protease enzyme of SARS-CoV-2, which directly involves the processing and release of translated non-structural proteins (nsps), and therefore involves the development of virus pathogenesis along with outbreak the forecasting of COVID-19 symptoms. Moreover, SARS-CoV-2 infections can be inhibited by plant-derived chemicals like amentoflavone derivatives, which could be used to develop an anti-COVID-19 drug. Our research study is designed to conduct an in silico analysis on derivatives of amentoflavone (isoginkgetin, putraflavone, 4''''''-methylamentoflavone, bilobetin, ginkgetin, sotetsuflavone, sequoiaflavone, heveaflavone, kayaflavone, and sciadopitysin) for targeting the non-structural protein of SARS-CoV-2, and subsequently further validate to confirm their antiviral ability. To conduct all the in silico experiments with the derivatives of amentoflavone against the M(PRO) protein, both computerized tools and online servers were applied; notably the software used is UCSF Chimera (version 1.14), PyRx, PyMoL, BIOVIA Discovery Studio tool (version 4.5), YASARA (dynamics simulator), and Cytoscape. Besides, as part of the online tools, the SwissDME and pKCSM were employed. The research study was proposed to implement molecular docking investigations utilizing compounds that were found to be effective against the viral primary protease (M(PRO)). M(PRO) protein interacted strongly with 10 amentoflavone derivatives. Every time, amentoflavone compounds outperformed the FDA-approved antiviral medicine that is currently underused in COVID-19 in terms of binding affinity (- 8.9, - 9.4, - 9.7, - 9.1, - 9.3, - 9.0, - 9.7, - 9.3, - 8.8, and - 9.0 kcal/mol, respectively). The best-selected derivatives of amentoflavone also possessed potential results in 100 ns molecular dynamic simulation (MDS) validation. It is conceivable that based on our in silico research these selected amentoflavone derivatives more precisely 4''''''-methylamentoflavone, ginkgetin, and sequoiaflavone have potential for serving as promising lead drugs against SARS-CoV-2 infection. In consequence, it is recommended that additional in vitro as well as in vivo research studies have to be conducted to support the conclusions of this current research study. CI - (c) 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Dey, Dipta AU - Dey D AD - Department of Biochemistry and Molecular Biology, Life Science Faculty, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, Dhaka, 8100, Bangladesh. FAU - Hossain, Rajib AU - Hossain R AD - Department of Pharmacy, Life Science Faculty, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, Dhaka, 8100, Bangladesh. FAU - Biswas, Partha AU - Biswas P AUID- ORCID: 0000-0002-9766-756X AD - Department of Genetic Engineering and Biotechnology, Faculty of Biological Science and Technology, Jashore University of Science and Technology (JUST), Jashore, 7408, Bangladesh. partha_160626@just.edu.bd. FAU - Paul, Priyanka AU - Paul P AD - Department of Biochemistry and Molecular Biology, Life Science Faculty, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, Dhaka, 8100, Bangladesh. FAU - Islam, Md Aminul AU - Islam MA AD - Department of Genetic Engineering and Biotechnology, Faculty of Biological Science and Technology, Jashore University of Science and Technology (JUST), Jashore, 7408, Bangladesh. FAU - Ema, Tanzila Ismail AU - Ema TI AD - Department of Biochemistry and Microbiology, North South University, Dhaka, 1229, Bangladesh. FAU - Gain, Bibhuti Kumar AU - Gain BK AD - Department of Genetic Engineering and Biotechnology, Faculty of Biological Science and Technology, Jashore University of Science and Technology (JUST), Jashore, 7408, Bangladesh. FAU - Hasan, Mohammad Mehedi AU - Hasan MM AD - Department of Biochemistry and Molecular Biology, Faculty of Life Science, Mawlana Bhashani Science and Technology University, Tangail, Bangladesh. FAU - Bibi, Shabana AU - Bibi S AD - Yunnan Herbal Laboratory, College of Ecology and Environmental Sciences, Yunnan University, Kunming, 650091, China. AD - Department of Biological Sciences, International Islamic University, Islamabad, Pakistan. FAU - Islam, Muhammad Torequl AU - Islam MT AD - Department of Pharmacy, Life Science Faculty, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, Dhaka, 8100, Bangladesh. FAU - Rahman, Md Ataur AU - Rahman MA AD - Global Biotechnology & Biomedical Research Network (GBBRN), Department of Biotechnology and Genetic Engineering, Faculty of Biological Sciences, Islamic University, Kushtia, 7003, Bangladesh. AD - Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Korea. AD - Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Korea. FAU - Kim, Bonglee AU - Kim B AD - Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Korea. bongleekim@khu.ac.kr. AD - Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul, 02447, Korea. bongleekim@khu.ac.kr. LA - eng GR - 27302C0038/ES/NIEHS NIH HHS/United States PT - Journal Article DEP - 20220531 PL - Netherlands TA - Mol Divers JT - Molecular diversity JID - 9516534 RN - 9I1VC79L77 (amentoflavone) RN - 0 (Protease Inhibitors) RN - 0 (Viral Nonstructural Proteins) RN - 0 (Antiviral Agents) RN - EC 3.4.- (Peptide Hydrolases) SB - IM MH - Humans MH - *SARS-CoV-2/metabolism MH - *COVID-19 MH - Molecular Docking Simulation MH - Molecular Dynamics Simulation MH - Network Pharmacology MH - Protease Inhibitors/chemistry MH - Viral Nonstructural Proteins MH - Antiviral Agents/chemistry MH - Peptide Hydrolases/metabolism PMC - PMC9153225 OTO - NOTNLM OT - ADMET OT - Amentoflavone derivatives OT - MPRO protein OT - Molecular dynamics study OT - Putraflavone OT - YASARA OT - nCoV-19 COIS- The authors declared no conflict of interest. EDAT- 2022/06/01 06:00 MHDA- 2023/05/10 06:42 PMCR- 2022/05/31 CRDT- 2022/05/31 15:41 PHST- 2022/03/13 00:00 [received] PHST- 2022/05/07 00:00 [accepted] PHST- 2023/05/10 06:42 [medline] PHST- 2022/06/01 06:00 [pubmed] PHST- 2022/05/31 15:41 [entrez] PHST- 2022/05/31 00:00 [pmc-release] AID - 10.1007/s11030-022-10459-9 [pii] AID - 10459 [pii] AID - 10.1007/s11030-022-10459-9 [doi] PST - ppublish SO - Mol Divers. 2023 Apr;27(2):857-871. doi: 10.1007/s11030-022-10459-9. Epub 2022 May 31.