Exploring the therapeutic nature of limonoids and triterpenoids against SARS-CoV-2 by targeting nsp13, nsp14, and nsp15 through molecular docking and dynamics simulations

Abhilash, 2021, Second wave of COVID-19: unrelenting rampage of the SARS CoV-2 variants, Curr Med Issues, 19, 129, 10.4103/cmi.cmi_44_21 Pal, 2020, Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): an update, Cureus, 12 Beeraka, 2020, Strategies for targeting SARS CoV-2: small molecule inhibitors-the current status, Front Immunol, 11, 552925, 10.3389/fimmu.2020.552925 Eroshenko, 2020, Implications of antibody-dependent enhancement of infection for SARS-CoV-2 countermeasures, Nat Biotechnol, 38, 789, 10.1038/s41587-020-0577-1 Krammer, 2020, SARS-CoV-2 vaccines in development, Nature, 586, 516, 10.1038/s41586-020-2798-3 Suraphan, 2020, Dietary therapy and herbal medicine for COVID-19 prevention: a review and perspective, J Tradit Complement Med, 10, 420, 10.1016/j.jtcme.2020.05.004 Robson, 2020, Coronavirus RNA proofreading: molecular basis and therapeutic targeting, Mol Cell, 79, 710, 10.1016/j.molcel.2020.07.027 Jang, 2020, A high ATP concentration enhances the cooperative translocation of the SARS coronavirus helicases nsP13 in the unwinding of duplex RNA, Sci Rep, 10, 10.1038/s41598-020-61432-1 Shu, 2020, SARS-Coronavirus-2 Nsp13 possesses NTPase and RNA helicases activities that can Be inhibited by bismuth salts, Virol Sin, 35, 321, 10.1007/s12250-020-00242-1 Guo, 2021, SARS-CoV-2 non-structural protein 13 (nsp13) hijacks host deubiquitinase USP13 and counteracts host antiviral immune response, Signal Transduct Target Ther, 6, 10.1038/s41392-021-00509-3 White, 2020, Discovery of COVID-19 inhibitors targeting the SARS-CoV-2 Nsp13 helicases, J Phys Chem Lett, 11, 9144, 10.1021/acs.jpclett.0c02421 Kim, 2021, Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2, Commun Biol, 4, 193, 10.1038/s42003-021-01735-9 Bhardwaj, 2004, The severe acute respiratory syndrome coronavirus Nsp15 protein is an endoribonuclease that prefers manganese as a cofactor, J Virol, 78, 12218, 10.1128/JVI.78.22.12218-12224.2004 V’kovski, 2020, Coronavirus biology and replication: implications for SARS-CoV-2, Nat Rev Microbiol, 19, 155, 10.1038/s41579-020-00468-6 Tahir, 2021, Coronavirus genomic nsp14-ExoN, structure, role, mechanism, and potential application as a drug target, J Med Virol, 93, 4258, 10.1002/jmv.27009 Saramago, 2021, New targets for drug design: importance of nsp14/nsp10 complex formation for the 3’-5’ exoribonucleolytic activity on SARS-CoV-2, FEBS J, 10.1111/febs.15815 Jockusch, 2020, Sofosbuvir terminated RNA is more resistant to SARS-CoV-2 proofreader than RNA terminated by Remdesivir, Sci Rep, 10, 10.1038/s41598-020-73641-9 Fuzimoto, 2020, The antiviral and coronavirus-host protein pathways inhibiting properties of herbs and natural compounds - additional weapons in the fight against the COVID-19 pandemic?, J Tradit Complement Med, 10, 405, 10.1016/j.jtcme.2020.05.003 Vardhan, 2020, In silico ADMET and molecular docking study on searching potential inhibitors from limonoids and triterpenoids for COVID-19, Comput Biol Med, 124, 103936, 10.1016/j.compbiomed.2020.103936 Mehany, 2021, Polyphenols as promising biologically active substances for preventing SARS-CoV-2: a review with research evidence and underlying mechanisms, Food Biosci, 40, 100891, 10.1016/j.fbio.2021.100891 Vidoni, 2021, Targeting autophagy with natural products to prevent SARS-CoV-2 infection, J Tradit Complement Med Kousar, 2020, Phytochemicals from selective plants have promising potential against SARS-CoV-2: investigation and corroboration through molecular docking, MD simulations, and quantum computations, BioMed Res Int, 1, 10.1155/2020/6237160 Selvaraj, 2020, Structure-based virtual screening and molecular dynamics simulation of SARS-CoV-2 Guanine-N7 methyltransferase (nsp14) for identifying antiviral inhibitors against COVID-19, J Biomol Struct Dyn, 1 Fakhri, 2021, Targeting neurological manifestations of coronaviruses by candidate phytochemicals: a mechanistic approach, Front Pharmacol, 11, 10.3389/fphar.2020.621099 Zhao, 2021, Glycyrrhizic acid nanoparticles as antiviral and anti-inflammatory agents for COVID-19 treatment, ACS Appl Mater Interfaces, 13, 20995, 10.1021/acsami.1c02755 Stevaert, 2021, Betulonic acid derivatives interfering with human coronavirus 229E replication via the nsp15 endoribonuclease, J Med Chem, 64, 5632, 10.1021/acs.jmedchem.0c02124 Vardhan, 2021, Virtual screening by targeting proteolytic sites of furin and TMPRSS2 to propose potential compounds obstructing the entry of SARS-CoV-2 virus into human host cells, J Tradit Complement Med Eswar, 2006, Comparative protein structure modeling using modeller, Curr Protoc Bioinformatics, 15, 10.1002/0471250953.bi0506s15 Khor, 2014, The structure and dynamics of BmR1 protein from Brugia malayi: in silico approaches, Int J Mol Sci, 15, 11082, 10.3390/ijms150611082 Daina, 2017, SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules, Sci Rep, 7, 10.1038/srep42717 Morris, 2009, AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility, J Comput Chem, 30, 2785, 10.1002/jcc.21256 Singh, 2014, Structure based virtual screening to identify inhibitors against MurE Enzyme of Mycobacterium tuberculosis using AutoDock Vina, Bioinformation, 10, 697, 10.6026/97320630010697 Morris, 2009, AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility, J Comput Chem, 30, 2785, 10.1002/jcc.21256 Huey, 2007, A semiempirical free energy force field with charge-based desolvation, J Comput Chem, 28, 1145, 10.1002/jcc.20634 Hess, 2008, GROMACS 4:algorithms for highly efficient ,load -Balanced,and scalable molecular simulation .J, Chem Theory Comput, 4, 435, 10.1021/ct700301q Jöhrer, 2020, Structure-guided identification of black cohosh (actaea racemosa) triterpenoids with in vitro activity against multiple myeloma, Molecules, 25, 766, 10.3390/molecules25040766 Hsu, 2014, Ganoderic acid and lucidenic acid (triterpenoid), Enzymes, 33, 10.1016/B978-0-12-802215-3.00003-3 Tian, 2006, Anti-cancer activity and mechanisms of 25-anhydrocimigenol-3-O-D-xylopyranoside isolated from Souliea vaginata on hepatomas, Anti Cancer Drugs, 17, 545, 10.1097/00001813-200606000-00008 Cicek, 2010, Bioactivity-guided isolation of GABAAReceptor modulating constituents from the rhizomes ofActaea racemosa, J Nat Prod, 73, 2024, 10.1021/np100479w 2016, Screening and identification of DPP-4 inhibitors from Xiaokean formula by a fluorescent probe, China J Chin Mater Med Talmon, 2020, Anti-inflammatory activity of absinthin and derivatives in human bronchoepithelial cells, J Nat Prod, 83, 1740, 10.1021/acs.jnatprod.9b00685 Korinek, 2021, Randialic acid B and tomentosolic acid block formyl peptide receptor 1 in human neutrophils and attenuate psoriasis-like inflammation in vivo, Biochem Pharmacol, 190, 114596, 10.1016/j.bcp.2021.114596 Tang, 2021, Shizukaol A exerts anti-inflammatory effect by regulating HMGB1/Nrf2/HO-1 pathway, Phytomedicine, 82, 153472, 10.1016/j.phymed.2021.153472 Fang, 2011, Lindenane disesquiterpenoids with anti-HIV-1 activity fromChloranthus japonicus, J Nat Prod, 74, 1408, 10.1021/np200087d 2003, Effect of limonin and nomilin on HIV-1 replication on infected human mononuclear cells, Planta Med, 69, 910, 10.1055/s-2003-45099 Fan, 2019, Limonin: a review of its pharmacology, toxicity, and pharmacokinetics, Molecules, 24, 3679, 10.3390/molecules24203679 Frick, 2006, Understanding helicase as a means of virus control, Curr Pharmaceut Des, 12, 1315, 10.2174/138161206776361147 Byrd, 2012, Superfamily 2 helicases, Front Biosci, 17, 2070, 10.2741/4038 Jia, 2019, Delicate structural coordination of the severe acute respiratory syndrome coronavirus Nsp13 upon ATP hydrolysis, Nucleic Acids Res, 47, 6538, 10.1093/nar/gkz409 Jankowsky, 2007, RNA helicase — one fold for many functions, Curr Opin Struct Biol, 17, 316, 10.1016/j.sbi.2007.05.007 Romano, 2020, A structural view of SARS-CoV-2 RNA replication machinery: RNA synthesis, proofreading and final capping, Cells, 9, 1267, 10.3390/cells9051267 Kumar, 2020, Exploiting existing molecular scaffolds for long-term COVID treatment, ACS Med Chem Lett, 11, 1357, 10.1021/acsmedchemlett.0c00254 Adedeji, 2014, Evaluation of SSYA10-001 as a replication inhibitor of severe acute respiratory syndrome, mouse hepatitis, and Middle East respiratory syndrome coronaviruses, Antimicrob Agents Chemother, 58, 4894, 10.1128/AAC.02994-14 Weng, 2007, The anti-invasive effect of lucidenic acids isolated from a newGanoderma lucidum strain, Mol Nutr Food Res, 51, 1472, 10.1002/mnfr.200700155 Sahoo, 2017, In vitro biological assessment of Homalium zeylanicum and isolation of lucidenic acid A triterpenoid, Toxicol Rep, 4, 274, 10.1016/j.toxrep.2017.04.004 Wu, 2016, The in vitro and in vivo antitumor activities of tetracyclic triterpenoids compounds actein and 26-deoxyactein isolated from rhizome of cimicifuga foetida L, Molecules, 21, 1001, 10.3390/molecules21081001 Ogando, 2020, The enzymatic activity of the nsp14 exoribonuclease is critical for replication of MERS-CoV and SARS-CoV-2, J Virol, 94, 10.1128/JVI.01246-20 Narayanan, 2021, Ritonavir may inhibit exoribonuclease activity of nsp14 from the SARS-CoV-2 virus and potentiate the activity of chain terminating drugs, Int J Biol Macromol, 168, 272, 10.1016/j.ijbiomac.2020.12.038 Squeglia, 2020, Host DDX helicase as possible SARS-CoV-2 proviral factors: a structural overview of their hijacking through multiple viral proteins, Front Chem, 8, 10.3389/fchem.2020.602162 Pillon, 2021, Cryo-EM structures of the SARS-CoV-2 endoribonuclease Nsp15 reveal insight into nuclease specificity and dynamics, Nat Commun, 12, 10.1038/s41467-020-20608-z Kim, 2020, Crystal structure of Nsp15 endoribonuclease NendoU from SARS-CoV -2, Protein Sci, 29, 1596, 10.1002/pro.3873 Bhardwaj, 2008, Structural and functional analyses of the severe acute respiratory syndrome coronavirus endoribonuclease Nsp15, J Biol Chem, 283, 3655, 10.1074/jbc.M708375200 Frazier, 2021 Mariano, 2020, Structural characterization of SARS-CoV-2: where we are, and where we need to Be, Front Mol Biosci, 7, 10.3389/fmolb.2020.605236 van de Sand, 2021, Glycyrrhizin effectively inhibits SARS-CoV-2 replication by inhibiting the viral main protease, Viruses, 13, 609, 10.3390/v13040609 Cinatl, 2003, Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus, Lancet, 361, 2045, 10.1016/S0140-6736(03)13615-X Wen, 2007, Specific plant terpenoids and lignoids possess potent antiviral activities against severe acute respiratory syndrome coronavirus, J Med Chem, 50, 4087, 10.1021/jm070295s Kumar, 2021, Identification of phytochemicals as potential therapeutic agents that binds to Nsp15 protein target of coronavirus (SARS-CoV-2) that are capable of inhibiting virus replication, Phytomedicine, 85, 153317, 10.1016/j.phymed.2020.153317 Balestrieri, 2011, Antiviral activity of seed extract from Citrus bergamia towards human retroviruses, Bioorg Med Chem, 19, 2084, 10.1016/j.bmc.2011.01.024