Generic placeholder image

Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Review Article

Natural Products as Potential Therapeutic Agents for SARS-CoV-2: A Medicinal Chemistry Perspective

Author(s): Varun Aggarwal, Ekta Bala, Pawan Kumar, Pankaj Raizada, Pardeep Singh and Praveen Kumar Verma*

Volume 23, Issue 17, 2023

Published on: 15 May, 2023

Page: [1664 - 1698] Pages: 35

DOI: 10.2174/1568026623666230327125918

Price: $65

conference banner
Abstract

Coronavirus is a single-stranded RNA virus discovered by virologist David Tyrrell in 1960. Till now seven human corona viruses have been identified including HCoV-229E, HCoVOC43, HCoV-NL63, HCoV-HKU1, SARS-CoV, MERS-CoV and SARS-CoV-2. In the present scenario, the SARS-CoV-2 outbreak causing SARS-CoV-2 pandemic, became the most serious public health emergency of the century worldwide. Natural products have long history and advantages for the drug discovery process. Almost 80% of drugs present in market are evolved from the natural resources. With the outbreak of SARS-CoV-2 pandemic, natural product chemists have made significant efforts for the identification of natural molecules which can be effective against the SARSCoV- 2. In current compilation we have discussed in vitro and in vivo anti-viral potential of natural product-based leads for the treatment of SARS-CoV-2. We have classified these leads in different classes of natural products such as alkaloids, terpenoids, flavonoids, polyphenols, quinones, cannabinoids, steroids, glucosinolates, diarylheptanoids, etc. and discussed the efficacy and mode of action of these natural molecules. The present review will surely opens new direction in future for the development of promising drug candidates, particularly from the natural origin against coronaviruses and other viral diseases.

Keywords: Natural products, SARS-CoV-2, Antiviral compounds, Secondary metabolites, Therapeutic targets, Medicinal chemistry.

« Previous
Graphical Abstract
[1]
Tyrrell, D.A.J.; Bynoe, M.L. Cultivation of a novel type of common-cold virus in organ cultures. BMJ, 1965, 1(5448), 1467-1470.
[http://dx.doi.org/10.1136/bmj.1.5448.1467] [PMID: 14288084]
[2]
Mahase, E. Covid-19: First coronavirus was described in The BMJ in 1965. BMJ, 2020, 369, m1547.
[http://dx.doi.org/10.1136/bmj.m1547] [PMID: 32299810]
[3]
Almeida, J.D.; Tyrrell, D.A.J. The morphology of three previously uncharacterized human respiratory viruses that grow in organ culture. J. Gen. Virol., 1967, 1(2), 175-178.
[http://dx.doi.org/10.1099/0022-1317-1-2-175] [PMID: 4293939]
[4]
Hierholzer, J.C.; Kemp, M.C.; Tannock, G.A. The RNA and proteins of human coronaviruses. Adv. Exp. Med. Biol., 1981, 142, 43-67.
[http://dx.doi.org/10.1007/978-1-4757-0456-3_4] [PMID: 7337042]
[5]
Ghosh, A.K.; Brindisi, M.; Shahabi, D.; Chapman, M.E.; Mesecar, A.D. Drug development and medicinal chemistry efforts toward SARS-coronavirus and covid-19 Therapeutics. ChemMedChem, 2020, 15(11), 907-932.
[http://dx.doi.org/10.1002/cmdc.202000223] [PMID: 32324951]
[6]
Peiris, J.S.M.; Guan, Y.; Yuen, K.Y. Severe acute respiratory syndrome. Nat. Med., 2004, 10(Suppl. 12), S88-S97.
[http://dx.doi.org/10.1038/nm1143] [PMID: 15577937]
[7]
Pyrc, K.; Berkhout, B.; van der Hoek, L. Identification of new human coronaviruses. Expert Rev. Anti Infect. Ther., 2007, 5(2), 245-253.
[http://dx.doi.org/10.1586/14787210.5.2.245] [PMID: 17402839]
[8]
Drosten, C.; Günther, S.; Preiser, W.; van der Werf, S.; Brodt, H.R.; Becker, S.; Rabenau, H.; Panning, M.; Kolesnikova, L.; Fouchier, R.A.M.; Berger, A.; Burguière, A.M.; Cinatl, J.; Eickmann, M.; Escriou, N.; Grywna, K.; Kramme, S.; Manuguerra, J.C.; Müller, S.; Rickerts, V.; Stürmer, M.; Vieth, S.; Klenk, H.D.; Osterhaus, A.D.M.E.; Schmitz, H.; Doerr, H.W. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N. Engl. J. Med., 2003, 348(20), 1967-1976.
[http://dx.doi.org/10.1056/NEJMoa030747] [PMID: 12690091]
[9]
Christian, M.D.; Poutanen, S.M.; Loutfy, M.R.; Muller, M.P.; Low, D.E. Severe acute respiratory syndrome. Clin. Infect. Dis., 2004, 38(10), 1420-1427.
[http://dx.doi.org/10.1086/420743] [PMID: 15156481]
[10]
Memish, Z.A.; Zumla, A.I.; Al-Hakeem, R.F.; Al-Rabeeah, A.A.; Stephens, G.M. Family cluster of Middle East respiratory syndrome coronavirus infections. N. Engl. J. Med., 2013, 368(26), 2487-2494.
[http://dx.doi.org/10.1056/NEJMoa1303729] [PMID: 23718156]
[11]
Rahman, A.; Sarkar, A. Risk factors for fatal middle east respiratory syndrome coronavirus infections in Saudi Arabia: Analysis of the WHO line list, 2013-2018. Am. J. Public Health, 2019, 109(9), 1288-1293.
[http://dx.doi.org/10.2105/AJPH.2019.305186] [PMID: 31318592]
[12]
Hu, S.; Jiang, S.; Qi, X.; Bai, R.; Ye, X.Y.; Xie, T. Races of small molecule clinical trials for the treatment of COVID‐19: An up‐to‐date comprehensive review. Drug Dev. Res., 2022, 83(1), 16-54.
[http://dx.doi.org/10.1002/ddr.21895] [PMID: 34762760]
[13]
Antonio, A.S.; Wiedemann, L.S.M.; Veiga-Junior, V.F. Natural products’ role against COVID-19. RSC Advances, 2020, 10(39), 23379-23393.
[http://dx.doi.org/10.1039/D0RA03774E] [PMID: 35693131]
[14]
Chakravarti, R.; Singh, R.; Ghosh, A.; Dey, D.; Sharma, P.; Velayutham, R.; Roy, S.; Ghosh, D. A review on potential of natural products in the management of COVID-19. RSC Advances, 2021, 11(27), 16711-16735.
[http://dx.doi.org/10.1039/D1RA00644D] [PMID: 35479175]
[15]
Chapman, R.L.; Andurkar, S.V. A review of natural products, their effects on SARS-CoV-2 and their utility as lead compounds in the discovery of drugs for the treatment of COVID-19. Med. Chem. Res., 2022, 31(1), 40-51.
[http://dx.doi.org/10.1007/s00044-021-02826-2] [PMID: 34873386]
[16]
Merarchi, M.; Dudha, N.; Das, B.C.; Garg, M. Natural products and phytochemicals as potential ANTI‐SARS‐COV ‐2 drugs. Phytother. Res., 2021, 35(10), 5384-5396.
[http://dx.doi.org/10.1002/ptr.7151] [PMID: 34132421]
[17]
Gu, J.; Gui, Y.; Chen, L.; Yuan, G.; Lu, H.Z.; Xu, X. Use of natural products as chemical library for drug discovery and network pharmacology. PLoS One, 2013, 8(4), e62839.
[http://dx.doi.org/10.1371/journal.pone.0062839] [PMID: 23638153]
[18]
Chassagne, F.; Cabanac, G.; Hubert, G.; David, B.; Marti, G. The landscape of natural product diversity and their pharmacological relevance from a focus on the Dictionary of Natural Products®. Phytochem. Rev., 2019, 18(3), 601-622.
[http://dx.doi.org/10.1007/s11101-019-09606-2]
[19]
Lockermann, G. Friedrich Wilhelm Serturner, the discoverer of morphine. J. Chem. Educ., 1951, 28(5), 277-279.
[http://dx.doi.org/10.1021/ed028p277]
[20]
Newman, D.J.; Cragg, G.M. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. J. Nat. Prod., 2020, 83(3), 770-803.
[http://dx.doi.org/10.1021/acs.jnatprod.9b01285] [PMID: 32162523]
[21]
Atanasov, A.G.; Zotchev, S.B.; Dirsch, V.M.; Supuran, C.T. Natural products in drug discovery: advances and opportunities. Nat. Rev. Drug Discov., 2021, 20(3), 200-216.
[http://dx.doi.org/10.1038/s41573-020-00114-z] [PMID: 33510482]
[22]
Kabir, A.; Muth, A. Polypharmacology: The science of multi-targeting molecules. Pharmacol. Res., 2022, 176, 106055.
[http://dx.doi.org/10.1016/j.phrs.2021.106055] [PMID: 34990865]
[23]
Reddy, A.S.; Zhang, S. Polypharmacology: Drug discovery for the future. Expert Rev. Clin. Pharmacol., 2013, 6(1), 41-47.
[http://dx.doi.org/10.1586/ecp.12.74] [PMID: 23272792]
[24]
Hopkins, A.L. Network pharmacology: The next paradigm in drug discovery. Nat. Chem. Biol., 2008, 4(11), 682-690.
[http://dx.doi.org/10.1038/nchembio.118] [PMID: 18936753]
[25]
Hopkins, A.L. Network pharmacology. Nat. Biotechnol., 2007, 25(10), 1110-1111.
[http://dx.doi.org/10.1038/nbt1007-1110] [PMID: 17921993]
[26]
Yıldırım, M.A.; Goh, K.I.; Cusick, M.E.; Barabási, A.L.; Vidal, M. Drug-Target network. Nat. Biotechnol., 2007, 25(10), 1119-1126.
[http://dx.doi.org/10.1038/nbt1338] [PMID: 17921997]
[27]
Durrant, J.D.; Amaro, R.E.; Xie, L.; Urbaniak, M.D.; Ferguson, M.A.J.; Haapalainen, A.; Chen, Z.; Di Guilmi, A.M.; Wunder, F.; Bourne, P.E.; McCammon, J.A. A multidimensional strategy to detect polypharmacological targets in the absence of structural and sequence homology. PLOS Comput. Biol., 2010, 6(1), e1000648.
[http://dx.doi.org/10.1371/journal.pcbi.1000648] [PMID: 20098496]
[28]
Oprea, T.I.; Mestres, J. Drug repurposing: Far beyond new targets for old drugs. AAPS J., 2012, 14(4), 759-763.
[http://dx.doi.org/10.1208/s12248-012-9390-1] [PMID: 22826034]
[29]
Oprea, T.I.; Nielsen, S.K.; Ursu, O.; Yang, J.J.; Taboureau, O.; Mathias, S.L.; Kouskoumvekaki, I.; Sklar, L.A.; Bologa, C.G. Associating drugs, targets and clinical outcomes into an integrated network affords a new platform for computer-aided drug repurposing. Mol. Inform., 2011, 30(2-3), 100-111.
[http://dx.doi.org/10.1002/minf.201100023] [PMID: 22287994]
[30]
Boran, A.D.W.; Iyengar, R. Systems approaches to polypharmacology and drug discovery. Curr. Opin. Drug Discov. Devel., 2010, 13(3), 297-309.
[PMID: 20443163]
[31]
Boran, A.D.W.; Iyengar, R. Systems pharmacology. Mt. Sinai J. Med., 2010, 77(4), 333-344.
[http://dx.doi.org/10.1002/msj.20191] [PMID: 20687178]
[32]
Xie, L.; Xie, L.; Kinnings, S.L.; Bourne, P.E. Novel computational approaches to polypharmacology as a means to define responses to individual drugs. Annu. Rev. Pharmacol. Toxicol., 2012, 52(1), 361-379.
[http://dx.doi.org/10.1146/annurev-pharmtox-010611-134630] [PMID: 22017683]
[33]
Achenbach, J.; Tiikkainen, P.; Franke, L.; Proschak, E. Computational tools for polypharmacology and repurposing. Future Med. Chem., 2011, 3(8), 961-968.
[http://dx.doi.org/10.4155/fmc.11.62] [PMID: 21707399]
[34]
Kilani-Jaziri, S.; Mokdad-Bzeouich, I.; Krifa, M.; Nasr, N.; Ghedira, K.; Chekir-Ghedira, L. Immunomodulatory and cellular anti-oxidant activities of caffeic, ferulic, and p -coumaric phenolic acids: A structure-activity relationship study. Drug Chem. Toxicol., 2017, 40(4), 416-424.
[http://dx.doi.org/10.1080/01480545.2016.1252919] [PMID: 27855523]
[35]
Mohamed, S.I.A.; Jantan, I.; Haque, M.A. Naturally occurring immunomodulators with antitumor activity: An insight on their mechanisms of action. Int. Immunopharmacol., 2017, 50, 291-304.
[http://dx.doi.org/10.1016/j.intimp.2017.07.010] [PMID: 28734166]
[36]
Islam, M.N.; Hossain, K.S.; Sarker, P.P.; Ferdous, J.; Hannan, M.A.; Rahman, M.M.; Chu, D.T.; Uddin, M.J. Revisiting pharmacological potentials ofNIGELLA SATIVA seed: A promising option for COVID ‐19 prevention and cure. Phytother. Res., 2021, 35(3), 1329-1344.
[http://dx.doi.org/10.1002/ptr.6895] [PMID: 33047412]
[37]
Zhong, J.; Tang, J.; Ye, C.; Dong, L. The immunology of COVID-19: Is immune modulation an option for treatment? Lancet Rheumatol., 2020, 2(7), e428-e436.
[http://dx.doi.org/10.1016/S2665-9913(20)30120-X] [PMID: 32835246]
[38]
Xu, X.; Chen, P.; Wang, J.; Feng, J.; Zhou, H.; Li, X.; Zhong, W.; Hao, P. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci. China Life Sci., 2020, 63(3), 457-460.
[http://dx.doi.org/10.1007/s11427-020-1637-5] [PMID: 32009228]
[39]
Zhou, P.; Yang, X.L.; Wang, X.G.; Hu, B.; Zhang, L.; Zhang, W.; Si, H.R.; Zhu, Y.; Li, B.; Huang, C.L.; Chen, H.D.; Chen, J.; Luo, Y.; Guo, H.; Jiang, R.D.; Liu, M.Q.; Chen, Y.; Shen, X.R.; Wang, X.; Zheng, X.S.; Zhao, K.; Chen, Q.J.; Deng, F.; Liu, L.L.; Yan, B.; Zhan, F.X.; Wang, Y.Y.; Xiao, G.F.; Shi, Z.L. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 2020, 579(7798), 270-273.
[http://dx.doi.org/10.1038/s41586-020-2012-7] [PMID: 32015507]
[40]
Zhou, F.; Yu, T.; Du, R.; Fan, G.; Liu, Y.; Liu, Z.; Xiang, J.; Wang, Y.; Song, B.; Gu, X.; Guan, L.; Wei, Y.; Li, H.; Wu, X.; Xu, J.; Tu, S.; Zhang, Y.; Chen, H.; Cao, B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet, 2020, 395(10229), 1054-1062.
[http://dx.doi.org/10.1016/S0140-6736(20)30566-3] [PMID: 32171076]
[41]
Li, G.; Fan, Y.; Lai, Y.; Han, T.; Li, Z.; Zhou, P.; Pan, P.; Wang, W.; Hu, D.; Liu, X.; Zhang, Q.; Wu, J. Coronavirus infections and immune responses. J. Med. Virol., 2020, 92(4), 424-432.
[http://dx.doi.org/10.1002/jmv.25685] [PMID: 31981224]
[42]
Li, X.; Geng, M.; Peng, Y.; Meng, L.; Lu, S. Molecular immune pathogenesis and diagnosis of COVID-19. J. Pharm. Anal., 2020, 10(2), 102-108.
[http://dx.doi.org/10.1016/j.jpha.2020.03.001] [PMID: 32282863]
[43]
Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X.; Cheng, Z.; Yu, T.; Xia, J.; Wei, Y.; Wu, W.; Xie, X.; Yin, W.; Li, H.; Liu, M.; Xiao, Y.; Gao, H.; Guo, L.; Xie, J.; Wang, G.; Jiang, R.; Gao, Z.; Jin, Q.; Wang, J.; Cao, B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 2020, 395(10223), 497-506.
[http://dx.doi.org/10.1016/S0140-6736(20)30183-5] [PMID: 31986264]
[44]
Wang, D.; Hu, B.; Hu, C.; Zhu, F.; Liu, X.; Zhang, J.; Wang, B.; Xiang, H.; Cheng, Z.; Xiong, Y.; Zhao, Y.; Li, Y.; Wang, X.; Peng, Z. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA, 2020, 323(11), 1061-1069.
[http://dx.doi.org/10.1001/jama.2020.1585] [PMID: 32031570]
[45]
Dandekar, A.A.; Perlman, S. Immunopathogenesis of coronavirus infections: Implications for SARS. Nat. Rev. Immunol., 2005, 5(12), 917-927.
[http://dx.doi.org/10.1038/nri1732] [PMID: 16322745]
[46]
Shah, M.A.; Rasul, A.; Yousaf, R.; Haris, M.; Faheem, H.I.; Hamid, A.; Khan, H.; Khan, A.H.; Aschner, M.; Batiha, G.E.S. Combination of natural antivirals and potent immune invigorators: A natural remedy to combat COVID ‐19. Phytother. Res., 2021, 35(12), 6530-6551.
[http://dx.doi.org/10.1002/ptr.7228] [PMID: 34396612]
[47]
Lai, X.; Pei, Q.; Song, X.; Zhou, X.; Yin, Z.; Jia, R.; Zou, Y.; Li, L.; Yue, G.; Liang, X.; Yin, L.; Lv, C.; Jing, B. The enhancement of immune function and activation of NF-κB by resveratrol-treatment in immunosuppressive mice. Int. Immunopharmacol., 2016, 33, 42-47.
[http://dx.doi.org/10.1016/j.intimp.2016.01.028] [PMID: 26854575]
[48]
van der Hoek, L.; Pyrc, K.; Jebbink, M.F.; Vermeulen-Oost, W.; Berkhout, R.J.M.; Wolthers, K.C.; Wertheim-van Dillen, P.M.E.; Kaandorp, J.; Spaargaren, J.; Berkhout, B. Identification of a new human coronavirus. Nat. Med., 2004, 10(4), 368-373.
[http://dx.doi.org/10.1038/nm1024] [PMID: 15034574]
[49]
Yang, P.; Wang, X. COVID-19: A new challenge for human beings. Cell. Mol. Immunol., 2020, 17(5), 555-557.
[http://dx.doi.org/10.1038/s41423-020-0407-x] [PMID: 32235915]
[50]
Zhang, Y.Z.; Holmes, E.C. A genomic perspective on the origin and emergence of SARS-CoV-2. Cell, 2020, 181(2), 223-227.
[http://dx.doi.org/10.1016/j.cell.2020.03.035] [PMID: 32220310]
[51]
Khailany, R.A.; Safdar, M.; Ozaslan, M. Genomic characterization of a novel SARS-CoV-2. Gene Rep., 2020, 19(100682), 100682.
[http://dx.doi.org/10.1016/j.genrep.2020.100682] [PMID: 32300673]
[52]
Mousavizadeh, L.; Ghasemi, S. Genotype and phenotype of COVID-19: Their roles in pathogenesis. J. Microbiol. Immunol. Infect., 2021, 54(2), 159-163.
[http://dx.doi.org/10.1016/j.jmii.2020.03.022] [PMID: 32265180]
[53]
Holmes, K.V. SARS-associated coronavirus. N. Engl. J. Med., 2003, 348(20), 1948-1951.
[http://dx.doi.org/10.1056/NEJMp030078] [PMID: 12748314]
[54]
Angeletti, S.; Benvenuto, D.; Bianchi, M.; Giovanetti, M.; Pascarella, S.; Ciccozzi, M. COVID‐2019: The role of the nsp2 and nsp3 in its pathogenesis. J. Med. Virol., 2020, 92(6), 584-588.
[http://dx.doi.org/10.1002/jmv.25719] [PMID: 32083328]
[55]
Helmy, Y.A.; Fawzy, M.; Elaswad, A.; Sobieh, A.; Kenney, S.P.; Shehata, A.A. The COVID-19 pandemic: A comprehensive review of taxonomy, genetics, epidemiology, diagnosis, treatment, and control. J. Clin. Med., 2020, 9(4), 1225.
[http://dx.doi.org/10.3390/jcm9041225] [PMID: 32344679]
[56]
Redondo, N.; Zaldívar-López, S.; Garrido, J.J.; Montoya, M. SARS-CoV-2 accessory proteins in viral pathogenesis: Knowns and unknowns. Front. Immunol., 2021, 12, 708264.
[http://dx.doi.org/10.3389/fimmu.2021.708264] [PMID: 34305949]
[57]
Yadav, R.; Chaudhary, J.K.; Jain, N.; Chaudhary, P.K.; Khanra, S.; Dhamija, P.; Sharma, A.; Kumar, A.; Handu, S. Role of structural and non-structural proteins and therapeutic targets of SARS-CoV-2 for COVID-19. Cells, 2021, 10(4), 821.
[http://dx.doi.org/10.3390/cells10040821] [PMID: 33917481]
[58]
Yoshimoto, F.K. The proteins of severe acute respiratory syndrome coronavirus-2 (SARS CoV-2 or N-COV19), the cause of COVID-19. Protein J., 2020, 39(3), 198-216.
[http://dx.doi.org/10.1007/s10930-020-09901-4] [PMID: 32447571]
[59]
Chandwani, A.; Shuter, J. Lopinavir/ritonavir in the treatment of HIV-1 infection: a review. Ther. Clin. Risk Manag., 2008, 4(5), 1023-1033.
[PMID: 19209283]
[60]
Patick, A.K.; Potts, K.E. Protease inhibitors as antiviral agents. Clin. Microbiol. Rev., 1998, 11(4), 614-627.
[http://dx.doi.org/10.1128/CMR.11.4.614] [PMID: 9767059]
[61]
Anderson, J.; Schiffer, C.; Lee, S.K.; Swanstrom, R. Viral protease inhibitors. Handb. Exp. Pharmacol., 2009, 189(189), 85-110.
[http://dx.doi.org/10.1007/978-3-540-79086-0_4] [PMID: 19048198]
[62]
Sagawa, T.; Inoue, K.; Takano, H. Use of protease inhibitors for the prevention of COVID-19. Prev. Med., 2020, 141, 106280.
[http://dx.doi.org/10.1016/j.ypmed.2020.106280] [PMID: 33035549]
[63]
Petushkova, A.I.; Zamyatnin, A.A., Jr Papain-like proteases as coronaviral drug targets: Current inhibitors, opportunities, and limitations. Pharmaceuticals, 2020, 13(10), 277.
[http://dx.doi.org/10.3390/ph13100277] [PMID: 32998368]
[64]
Wu, F.; Zhao, S.; Yu, B.; Chen, Y.M.; Wang, W.; Song, Z.G.; Hu, Y.; Tao, Z.W.; Tian, J.H.; Pei, Y.Y.; Yuan, M.L.; Zhang, Y.L.; Dai, F.H.; Liu, Y.; Wang, Q.M.; Zheng, J.J.; Xu, L.; Holmes, E.C.; Zhang, Y.Z. A new coronavirus associated with human respiratory disease in China. Nature, 2020, 579(7798), 265-269.
[http://dx.doi.org/10.1038/s41586-020-2008-3] [PMID: 32015508]
[65]
Boras, B.; Jones, R.M.; Anson, B.J.; Arenson, D.; Aschenbrenner, L.; Bakowski, M.A.; Beutler, N.; Binder, J.; Chen, E.; Eng, H.; Hammond, H.; Hammond, J.; Haupt, R.E.; Hoffman, R.; Kadar, E.P.; Kania, R.; Kimoto, E.; Kirkpatrick, M.G.; Lanyon, L.; Lendy, E.K.; Lillis, J.R.; Logue, J.; Luthra, S.A.; Ma, C.; Mason, S.W.; McGrath, M.E.; Noell, S.; Obach, R.S.; O’ Brien, M.N.; O’Connor, R.; Ogilvie, K.; Owen, D.; Pettersson, M.; Reese, M.R.; Rogers, T.F.; Rosales, R.; Rossulek, M.I.; Sathish, J.G.; Shirai, N.; Steppan, C.; Ticehurst, M.; Updyke, L.W.; Weston, S.; Zhu, Y.; White, K.M.; García-Sastre, A.; Wang, J.; Chatterjee, A.K.; Mesecar, A.D.; Frieman, M.B.; Anderson, A.S.; Allerton, C. Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID19. Nat. Commun., 2021, 12(1), 6055.
[http://dx.doi.org/10.1038/s41467-021-26239-2] [PMID: 34663813]
[66]
Pillaiyar, T.; Manickam, M.; Namasivayam, V.; Hayashi, Y.; Jung, S.H. An overview of severe acute respiratory syndrome-coronavirus (SARS-CoV) 3CL protease inhibitors: Peptidomimetics and small molecule chemotherapy. J. Med. Chem., 2016, 59(14), 6595-6628.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01461] [PMID: 26878082]
[67]
Jin, Z.; Du, X.; Xu, Y.; Deng, Y.; Liu, M.; Zhao, Y.; Zhang, B.; Li, X.; Zhang, L.; Peng, C.; Duan, Y.; Yu, J.; Wang, L.; Yang, K.; Liu, F.; Jiang, R.; Yang, X.; You, T.; Liu, X.; Yang, X.; Bai, F.; Liu, H.; Liu, X.; Guddat, L.W.; Xu, W.; Xiao, G.; Qin, C.; Shi, Z.; Jiang, H.; Rao, Z.; Yang, H. Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature, 2020, 582(7811), 289-293.
[http://dx.doi.org/10.1038/s41586-020-2223-y] [PMID: 32272481]
[68]
Owen, D.R.; Allerton, C.M.N.; Anderson, A.S.; Aschenbrenner, L.; Avery, M.; Berritt, S.; Boras, B.; Cardin, R.D.; Carlo, A.; Coffman, K.J.; Dantonio, A.; Di, L.; Eng, H.; Ferre, R.; Gajiwala, K.S.; Gibson, S.A.; Greasley, S.E.; Hurst, B.L.; Kadar, E.P.; Kalgutkar, A.S.; Lee, J.C.; Lee, J.; Liu, W.; Mason, S.W.; Noell, S.; Novak, J.J.; Obach, R.S.; Ogilvie, K.; Patel, N.C.; Pettersson, M.; Rai, D.K.; Reese, M.R.; Sammons, M.F.; Sathish, J.G.; Singh, R.S.P.; Steppan, C.M.; Stewart, A.E.; Tuttle, J.B.; Updyke, L.; Verhoest, P.R.; Wei, L.; Yang, Q.; Zhu, Y. An oral SARS-CoV-2 M pro inhibitor clinical candidate for the treatment of COVID-19. Science, 2021, 374(6575), 1586-1593.
[http://dx.doi.org/10.1126/science.abl4784] [PMID: 34726479]
[69]
Ma, C.; Sacco, M.D.; Hurst, B.; Townsend, J.A.; Hu, Y.; Szeto, T.; Zhang, X.; Tarbet, B.; Marty, M.T.; Chen, Y.; Wang, J. Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease. Cell Res., 2020, 30(8), 678-692.
[http://dx.doi.org/10.1038/s41422-020-0356-z] [PMID: 32541865]
[70]
Sacco, M.D.; Ma, C.; Lagarias, P.; Gao, A.; Townsend, J.A.; Meng, X.; Dube, P.; Zhang, X.; Hu, Y.; Kitamura, N.; Hurst, B.; Tarbet, B.; Marty, M.T.; Kolocouris, A.; Xiang, Y.; Chen, Y.; Wang, J. Structure and inhibition of the SARS-CoV-2 main protease reveal strategy for developing dual inhibitors against M pro and cathepsin L. Sci. Adv., 2020, 6(50), eabe0751.
[http://dx.doi.org/10.1126/sciadv.abe0751] [PMID: 33158912]
[71]
Rut, W.; Groborz, K.; Zhang, L.; Sun, X.; Zmudzinski, M.; Pawlik, B.; Mlynarski, W.; Hilgenfeld, R.; Drag, M. Substrate specificity profiling of SARS-CoV-2 main protease enables design of activity-based probes for patient-sample imaging. bioRxiv, 2020, 981928.
[http://dx.doi.org/10.1101/2020.03.07.981928]
[72]
Harcourt, B.H.; Jukneliene, D.; Kanjanahaluethai, A.; Bechill, J.; Severson, K.M.; Smith, C.M.; Rota, P.A.; Baker, S.C. Identification of severe acute respiratory syndrome coronavirus replicase products and characterization of papain-like protease activity. J. Virol., 2004, 78(24), 13600-13612.
[http://dx.doi.org/10.1128/JVI.78.24.13600-13612.2004] [PMID: 15564471]
[73]
Lim, K.P.; Ng, L.F.P.; Liu, D.X. Identification of a novel cleavage activity of the first papain-like proteinase domain encoded by open reading frame 1a of the coronavirus Avian infectious bronchitis virus and characterization of the cleavage products. J. Virol., 2000, 74(4), 1674-1685.
[http://dx.doi.org/10.1128/JVI.74.4.1674-1685.2000] [PMID: 10644337]
[74]
Frieman, M.; Ratia, K.; Johnston, R.E.; Mesecar, A.D.; Baric, R.S. Severe acute respiratory syndrome coronavirus papain-like protease ubiquitin-like domain and catalytic domain regulate antagonism of IRF3 and NF-kappaB signaling. J. Virol., 2009, 83(13), 6689-6705.
[http://dx.doi.org/10.1128/JVI.02220-08] [PMID: 19369340]
[75]
Devaraj, S.G.; Wang, N.; Chen, Z.; Chen, Z.; Tseng, M.; Barretto, N.; Lin, R.; Peters, C.J.; Tseng, C.T.K.; Baker, S.C.; Li, K. Regulation of IRF-3-dependent innate immunity by the papain-like protease domain of the severe acute respiratory syndrome coronavirus. J. Biol. Chem., 2007, 282(44), 32208-32221.
[http://dx.doi.org/10.1074/jbc.M704870200] [PMID: 17761676]
[76]
Bailey-Elkin, B.A.; Knaap, R.C.M.; Johnson, G.G.; Dalebout, T.J.; Ninaber, D.K.; van Kasteren, P.B.; Bredenbeek, P.J.; Snijder, E.J.; Kikkert, M.; Mark, B.L. Crystal structure of the Middle East respiratory syndrome coronavirus (MERS-CoV) papain-like protease bound to ubiquitin facilitates targeted disruption of deubiquitinating activity to demonstrate its role in innate immune suppression. J. Biol. Chem., 2014, 289(50), 34667-34682.
[http://dx.doi.org/10.1074/jbc.M114.609644] [PMID: 25320088]
[77]
Rut, W.; Lv, Z.; Zmudzinski, M.; Patchett, S.; Nayak, D.; Snipas, S.J.; El Oualid, F.; Huang, T.T.; Bekes, M.; Drag, M.; Olsen, S.K. Activity profiling and crystal structures of inhibitor-bound SARS-CoV-2 papain-like protease: A framework for anti-COVID-19 drug design. Sci. Adv., 2020, 6(42), eabd4596.
[http://dx.doi.org/10.1126/sciadv.abd4596] [PMID: 33067239]
[78]
Xian, Y.; Zhang, J.; Bian, Z.; Zhou, H.; Zhang, Z.; Lin, Z.; Xu, H. Bioactive natural compounds against human coronaviruses: a review and perspective. Acta Pharm. Sin. B, 2020, 10(7), 1163-1174.
[http://dx.doi.org/10.1016/j.apsb.2020.06.002] [PMID: 32834947]
[79]
Shin, D.; Mukherjee, R.; Grewe, D.; Bojkova, D.; Baek, K.; Bhattacharya, A.; Schulz, L.; Widera, M.; Mehdipour, A.R.; Tascher, G.; Geurink, P.P.; Wilhelm, A.; van der Heden van Noort, G.J.; Ovaa, H.; Müller, S.; Knobeloch, K.P.; Rajalingam, K.; Schulman, B.A.; Cinatl, J.; Hummer, G.; Ciesek, S.; Dikic, I. Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity. Nature, 2020, 587(7835), 657-662.
[http://dx.doi.org/10.1038/s41586-020-2601-5] [PMID: 32726803]
[80]
Ma, C.; Sacco, M.D.; Xia, Z.; Lambrinidis, G.; Townsend, J.A.; Hu, Y.; Meng, X.; Szeto, T.; Ba, M.; Zhang, X.; Gongora, M.; Zhang, F.; Marty, M.T.; Xiang, Y.; Kolocouris, A.; Chen, Y.; Wang, J. Discovery of SARS-CoV-2 Papain-like protease inhibitors through a combination of high-throughput screening and a flip GFP-based reporter assay. ACS Cent. Sci., 2021, 7(7), 1245-1260.
[http://dx.doi.org/10.1021/acscentsci.1c00519] [PMID: 34341772]
[81]
Clasman, J.R.; Everett, R.K.; Srinivasan, K.; Mesecar, A.D. Decoupling deISGylating and deubiquitinating activities of the MERS virus papain-like protease. Antiviral Res., 2020, 174, 104661.
[http://dx.doi.org/10.1016/j.antiviral.2019.104661] [PMID: 31765674]
[82]
Chen, X.; Yang, X.; Zheng, Y.; Yang, Y.; Xing, Y.; Chen, Z. SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex. Protein Cell, 2014, 5(5), 369-381.
[http://dx.doi.org/10.1007/s13238-014-0026-3] [PMID: 24622840]
[83]
Osipiuk, J.; Azizi, S.A.; Dvorkin, S.; Endres, M.; Jedrzejczak, R.; Jones, K.A.; Kang, S.; Kathayat, R.S.; Kim, Y.; Lisnyak, V.G.; Maki, S.L.; Nicolaescu, V.; Taylor, C.A.; Tesar, C.; Zhang, Y.A.; Zhou, Z.; Randall, G.; Michalska, K.; Snyder, S.A.; Dickinson, B.C.; Joachimiak, A. Structure of papain-like protease from SARS-CoV-2 and its complexes with non-covalent inhibitors. Nat. Commun., 2021, 12(1), 743.
[http://dx.doi.org/10.1038/s41467-021-21060-3] [PMID: 33531496]
[84]
de Farias, S.T.; dos Santos, A.P., Junior; Rêgo, T.G.; José, M.V. Origin and evolution of RNA-dependent RNA polymerase. Front. Genet., 2017, 8, 125.
[http://dx.doi.org/10.3389/fgene.2017.00125] [PMID: 28979293]
[85]
Venkataraman, S.; Prasad, B.; Selvarajan, R. RNA Dependent RNA polymerases: Insights from structure, function and evolution. Viruses, 2018, 10(2), 76.
[http://dx.doi.org/10.3390/v10020076] [PMID: 29439438]
[86]
Hansen, J.L.; Long, A.M.; Schultz, S.C. Structure of the RNA-dependent RNA polymerase of poliovirus. Structure, 1997, 5(8), 1109-1122.
[http://dx.doi.org/10.1016/S0969-2126(97)00261-X] [PMID: 9309225]
[87]
Vicenti, I.; Zazzi, M.; Saladini, F. SARS-CoV-2 RNA-dependent RNA polymerase as a therapeutic target for COVID-19. Expert Opin. Ther. Pat., 2021, 31(4), 325-337.
[http://dx.doi.org/10.1080/13543776.2021.1880568] [PMID: 33475441]
[88]
Gao, Y.; Yan, L.; Huang, Y.; Liu, F.; Zhao, Y.; Cao, L.; Wang, T.; Sun, Q.; Ming, Z.; Zhang, L.; Ge, J.; Zheng, L.; Zhang, Y.; Wang, H.; Zhu, Y.; Zhu, C.; Hu, T.; Hua, T.; Zhang, B.; Yang, X.; Li, J.; Yang, H.; Liu, Z.; Xu, W.; Guddat, L.W.; Wang, Q.; Lou, Z.; Rao, Z. Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science, 2020, 368(6492), 779-782.
[http://dx.doi.org/10.1126/science.abb7498] [PMID: 32277040]
[89]
Hillen, H.S.; Kokic, G.; Farnung, L.; Dienemann, C.; Tegunov, D.; Cramer, P. Structure of replicating SARS-CoV-2 polymerase. Nature, 2020, 584(7819), 154-156.
[http://dx.doi.org/10.1038/s41586-020-2368-8] [PMID: 32438371]
[90]
Machitani, M.; Yasukawa, M.; Nakashima, J.; Furuichi, Y.; Masutomi, K. RNA‐dependent RNA polymerase, RdRP, a promising therapeutic target for cancer and potentially COVID‐19. Cancer Sci., 2020, 111(11), 3976-3984.
[http://dx.doi.org/10.1111/cas.14618] [PMID: 32805774]
[91]
Tian, L.; Qiang, T.; Liang, C.; Ren, X.; Jia, M.; Zhang, J.; Li, J.; Wan, M.; YuWen, X.; Li, H.; Cao, W.; Liu, H. RNA-dependent RNA polymerase (RdRp) inhibitors: The current landscape and repurposing for the COVID-19 pandemic. Eur. J. Med. Chem., 2021, 213, 113201.
[http://dx.doi.org/10.1016/j.ejmech.2021.113201]
[92]
Wu, J.; Liu, W.; Gong, P. A structural overview of RNA-dependent RNA polymerases from the Flaviviridae family. Int. J. Mol. Sci., 2015, 16(12), 12943-12957.
[http://dx.doi.org/10.3390/ijms160612943] [PMID: 26062131]
[93]
Kumar, R.; Mishra, S.; Shreya; Maurya, S.K. Recent advances in the discovery of potent RNA-dependent RNA-polymerase (RdRp) inhibitors targeting viruses. RSC Medicinal Chemistry, 2021, 12(3), 306-320.
[http://dx.doi.org/10.1039/D0MD00318B] [PMID: 34046618]
[94]
Shi, M.; Wang, L.; Fontana, P.; Vora, S.; Zhang, Y.; Fu, T-M.; Lieberman, J.; Wu, H. SARS-CoV-2 Nsp1 suppresses host but not viral translation through a bipartite mechanism. BioRxiv, 2020.
[http://dx.doi.org/10.1101/2020.09.18.302901]
[95]
Huang, C.; Lokugamage, K.G.; Rozovics, J.M.; Narayanan, K.; Semler, B.L.; Makino, S. SARS coronavirus nsp1 protein induces template-dependent endonucleolytic cleavage of mRNAs: viral mRNAs are resistant to nsp1-induced RNA cleavage. PLoS Pathog., 2011, 7(12), e1002433.
[http://dx.doi.org/10.1371/journal.ppat.1002433] [PMID: 22174690]
[96]
Cornillez-Ty, C.T.; Liao, L.; Yates, J.R., III; Kuhn, P.; Buchmeier, M.J. Severe acute respiratory syndrome coronavirus nonstructural protein 2 interacts with a host protein complex involved in mitochondrial biogenesis and intracellular signaling. J. Virol., 2009, 83(19), 10314-10318.
[http://dx.doi.org/10.1128/JVI.00842-09] [PMID: 19640993]
[97]
Sundar, S.; Thangamani, L.; Piramanayagam, S.; Rahul, C.N.; Aiswarya, N.; Sekar, K.; Natarajan, J. Screening of FDA-approved compound library identifies potential small-molecule inhibitors of SARS-CoV-2 non-structural proteins NSP1, NSP4, NSP6 and NSP13: Molecular modeling and molecular dynamics studies. J. Proteins Proteom., 2021, 12(3), 161-175.
[http://dx.doi.org/10.1007/s42485-021-00067-w] [PMID: 34121824]
[98]
Ricciardi, S.; Guarino, A.M.; Giaquinto, L.; Polishchuk, E.V.; Santoro, M.; Di Tullio, G.; Wilson, C.; Panariello, F.; Soares, V.C.; Dias, S.S.G.; Santos, J.C.; Souza, T.M.L.; Fusco, G.; Viscardi, M.; Brandi, S.; Bozza, P.T.; Polishchuk, R.S.; Venditti, R.; De Matteis, M.A. The role of NSP6 in the biogenesis of the SARS-CoV-2 replication organelle. Nature, 2022, 606(7915), 761-768.
[http://dx.doi.org/10.1038/s41586-022-04835-6] [PMID: 35551511]
[99]
Peng, Q.; Peng, R.; Yuan, B.; Zhao, J.; Wang, M.; Wang, X.; Wang, Q.; Sun, Y.; Fan, Z.; Qi, J.; Gao, G.F.; Shi, Y. Structural and biochemical characterization of the nsp12-nsp7-nsp8 core polymerase complex from SARS-CoV-2. Cell Rep., 2020, 31(11), 107774.
[http://dx.doi.org/10.1016/j.celrep.2020.107774] [PMID: 32531208]
[100]
Wilamowski, M.; Hammel, M.; Leite, W.; Zhang, Q.; Kim, Y.; Weiss, K.L.; Jedrzejczak, R.; Rosenberg, D.J.; Fan, Y.; Wower, J.; Bierma, J.C.; Sarker, A.H.; Tsutakawa, S.E.; Pingali, S.V.; O’Neill, H.M.; Joachimiak, A.; Hura, G.L. Transient and stabilized complexes of Nsp7, Nsp8, and Nsp12 in SARS-CoV-2 replication. Biophys. J., 2021, 120(15), 3152-3165.
[http://dx.doi.org/10.1016/j.bpj.2021.06.006] [PMID: 34197805]
[101]
Gorkhali, R.; Koirala, P.; Rijal, S.; Mainali, A.; Baral, A.; Bhattarai, H.K. Structure and function of major SARS-CoV-2 and SARS-CoV Proteins. Bioinform. Biol. Insights, 2021, 15.
[http://dx.doi.org/10.1177/11779322211025876] [PMID: 34220199]
[102]
Makiyama, K.; Hazawa, M.; Kobayashi, A.; Lim, K.; Voon, D.C.; Wong, R.W. NSP9 of SARS-CoV-2 attenuates nuclear transport by hampering nucleoporin 62 dynamics and functions in host cells. Biochem. Biophys. Res. Commun., 2022, 586, 137-142.
[http://dx.doi.org/10.1016/j.bbrc.2021.11.046] [PMID: 34844119]
[103]
Romano, M.; Ruggiero, A.; Squeglia, F.; Maga, G.; Berisio, R. A Structural View of SARS-CoV-2 RNA replication machinery: RNA synthesis, proofreading and final capping. Cells, 2020, 9(5), 1267.
[http://dx.doi.org/10.3390/cells9051267] [PMID: 32443810]
[104]
Guo, G.; Gao, M.; Gao, X.; Zhu, B.; Huang, J.; Luo, K.; Zhang, Y.; Sun, J.; Deng, M.; Lou, Z. SARS-CoV-2 non-structural protein 13 (nsp13) hijacks host deubiquitinase USP13 and counteracts host antiviral immune response. Signal Transduct. Target. Ther., 2021, 6(1), 119.
[http://dx.doi.org/10.1038/s41392-021-00509-3] [PMID: 33707416]
[105]
Fung, S.Y.; Siu, K.L.; Lin, H.; Chan, C.P.; Yeung, M.L.; Jin, D.Y. SARS-CoV-2 NSP13 helicase suppresses interferon signaling by perturbing JAK1 phosphorylation of STAT1. Cell Biosci., 2022, 12(1), 36.
[http://dx.doi.org/10.1186/s13578-022-00770-1] [PMID: 35317858]
[106]
Corona, A.; Wycisk, K.; Talarico, C.; Manelfi, C.; Milia, J.; Cannalire, R.; Esposito, F.; Gribbon, P.; Zaliani, A.; Iaconis, D.; Beccari, A.R.; Summa, V.; Nowotny, M.; Tramontano, E. Natural compounds inhibit SARS-CoV-2 nsp13 unwinding and ATPase enzyme activities. ACS Pharmacol. Transl. Sci., 2022, 5(4), 226-239.
[http://dx.doi.org/10.1021/acsptsci.1c00253] [PMID: 35434533]
[107]
Zhang, S.; Wang, J.; Wang, L.; Aliyari, S.; Cheng, G. SARS-CoV-2 virus NSP14 Impairs NRF2/HMOX1 activation by targeting Sirtuin 1. Cell. Mol. Immunol., 2022, 19(8), 872-882.
[http://dx.doi.org/10.1038/s41423-022-00887-w] [PMID: 35732914]
[108]
Saramago, M.; Costa, V.; Souza, C.; Bárria, C.; Domingues, S.; Viegas, S.; Lousa, D.; Soares, C.; Arraiano, C.; Matos, R. The nsp15 Nuclease as a good target to combat SARS-CoV-2: Mechanism of action and its inactivation with FDA-approved drugs. Microorganisms, 2022, 10(2), 342.
[http://dx.doi.org/10.3390/microorganisms10020342] [PMID: 35208797]
[109]
Jiang, Y.; Liu, L.; Manning, M.; Bonahoom, M.; Lotvola, A.; Yang, Z.; Yang, Z.Q. Structural analysis, virtual screening and molecular simulation to identify potential inhibitors targeting 2′-O-ribose methyltransferase of SARS-CoV-2 coronavirus. J. Biomol. Struct. Dyn., 2022, 40(3), 1331-1346.
[http://dx.doi.org/10.1080/07391102.2020.1828172] [PMID: 33016237]
[110]
Ashour, H.M.; Elkhatib, W.F.; Rahman, M.M.; Elshabrawy, H.A. Insights into the recent 2019 novel coronavirus (SARS-CoV-2) in light of past human coronavirus outbreaks. Pathogens, 2020, 9(3), 186.
[http://dx.doi.org/10.3390/pathogens9030186] [PMID: 32143502]
[111]
Wrapp, D.; Wang, N.; Corbett, K.S.; Goldsmith, J.A.; Hsieh, C.L.; Abiona, O.; Graham, B.S.; McLellan, J.S. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science, 2020, 367(6483), 1260-1263.
[http://dx.doi.org/10.1126/science.abb2507] [PMID: 32075877]
[112]
Liu, Z.; Xiao, X.; Wei, X.; Li, J.; Yang, J.; Tan, H.; Zhu, J.; Zhang, Q.; Wu, J.; Liu, L. Composition and divergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS‐CoV‐2. J. Med. Virol., 2020, 92(6), 595-601.
[http://dx.doi.org/10.1002/jmv.25726] [PMID: 32100877]
[113]
Xia, S.; Zhu, Y.; Liu, M.; Lan, Q.; Xu, W.; Wu, Y.; Ying, T.; Liu, S.; Shi, Z.; Jiang, S.; Lu, L. Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein. Cell. Mol. Immunol., 2020, 17(7), 765-767.
[http://dx.doi.org/10.1038/s41423-020-0374-2] [PMID: 32047258]
[114]
Kumar, B.K.; Sekhar, K.V.; Kunjiappan, S.; Jamalis, J.; Balaña-Fouce, R.; Tekwani, B.L.; Sankaranarayanan, M. Druggable targets of SARS-CoV-2 and treatment opportunities for COVID-19. Bioorg. Chem., 2020, 104, 104269.
[http://dx.doi.org/10.1016/j.bioorg.2020.104269] [PMID: 32947136]
[115]
Hoffmann, M.; Kleine-Weber, H.; Schroeder, S.; Krüger, N.; Herrler, T.; Erichsen, S.; Schiergens, T.S.; Herrler, G.; Wu, N.H.; Nitsche, A.; Müller, M.A.; Drosten, C.; Pöhlmann, S. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell, 2020, 181(2), 271-280.e8.
[http://dx.doi.org/10.1016/j.cell.2020.02.052] [PMID: 32142651]
[116]
Walls, A.C.; Park, Y.J.; Tortorici, M.A.; Wall, A.; McGuire, A.T.; Veesler, D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell, 2020, 181(2), 281-292.e6.
[http://dx.doi.org/10.1016/j.cell.2020.02.058] [PMID: 32155444]
[117]
Rajarshi, K.; Khan, R.; Singh, M.K.; Ranjan, T.; Ray, S.; Ray, S. A structural analysis of M protein in coronavirus assembly and morphology. J. Struct. Biol., 2011, 174(1), 11-22.
[http://dx.doi.org/10.1016/j.jsb.2010.11.021]
[118]
McBride, R.; van Zyl, M.; Fielding, B. The coronavirus nucleocapsid is a multifunctional protein. Viruses, 2014, 6(8), 2991-3018.
[http://dx.doi.org/10.3390/v6082991] [PMID: 25105276]
[119]
Chang, C.; Sue, S.C.; Yu, T.; Hsieh, C.M.; Tsai, C.K.; Chiang, Y.C.; Lee, S.; Hsiao, H.; Wu, W.J.; Chang, W.L.; Lin, C.H.; Huang, T. Modular organization of SARS coronavirus nucleocapsid protein. J. Biomed. Sci., 2006, 13(1), 59-72.
[http://dx.doi.org/10.1007/s11373-005-9035-9] [PMID: 16228284]
[120]
Sheikh, A.; Al-Taher, A.; Al-Nazawi, M.; Al-Mubarak, A.I.; Kandeel, M. Analysis of preferred codon usage in the coronavirus N genes and their implications for genome evolution and vaccine design. J. Virol. Methods, 2020, 277, 113806.
[http://dx.doi.org/10.1016/j.jviromet.2019.113806] [PMID: 31911390]
[121]
Lutomski, C.A.; El-Baba, T.J.; Bolla, J.R.; Robinson, C.V. Autoproteolytic products of the SARS-CoV-2 nucleocapsid protein are primed for antibody evasion and virus proliferation. bioRxiv, 2020, 1-27.
[122]
Nieto-Torres, J.L.; DeDiego, M.L.; Verdiá-Báguena, C.; Jimenez-Guardeño, J.M.; Regla-Nava, J.A.; Fernandez-Delgado, R.; Castaño-Rodriguez, C.; Alcaraz, A.; Torres, J.; Aguilella, V.M.; Enjuanes, L. Severe acute respiratory syndrome coronavirus envelope protein ion channel activity promotes virus fitness and pathogenesis. PLoS Pathog., 2014, 10(5), e1004077.
[http://dx.doi.org/10.1371/journal.ppat.1004077] [PMID: 24788150]
[123]
Schoeman, D.; Fielding, B.C. Coronavirus envelope protein: current knowledge. Virol. J., 2019, 16(1), 69.
[http://dx.doi.org/10.1186/s12985-019-1182-0] [PMID: 31133031]
[124]
Teoh, K.T.; Siu, Y.L.; Chan, W.L.; Schlüter, M.A.; Liu, C.J.; Peiris, J.S.M.; Bruzzone, R.; Margolis, B.; Nal, B. The SARS coronavirus E protein interacts with PALS1 and alters tight junction formation and epithelial morphogenesis. Mol. Biol. Cell, 2010, 21(22), 3838-3852.
[http://dx.doi.org/10.1091/mbc.e10-04-0338] [PMID: 20861307]
[125]
Ujike, M.; Taguchi, F. Incorporation of spike and membrane glycoproteins into coronavirus virions. Viruses, 2015, 7(4), 1700-1725.
[http://dx.doi.org/10.3390/v7041700] [PMID: 25855243]
[126]
Bianchi, M.; Benvenuto, D.; Giovanetti, M.; Angeletti, S.; Ciccozzi, M.; Pascarella, S. SARS-CoV-2 envelope and membrane proteins: structural differences linked to virus characteristics? BioMed Res. Int., 2020, 2020, 1-6.
[http://dx.doi.org/10.1155/2020/4389089] [PMID: 32596311]
[127]
Cagliani, R.; Forni, D.; Clerici, M.; Sironi, M. Computational inference of selection underlying the evolution of the novel coronavirus, severe acute respiratory syndrome coronavirus 2. J. Virol., 2020, 94(12), e00411-e00420.
[http://dx.doi.org/10.1128/JVI.00411-20] [PMID: 32238584]
[128]
de Haan, C.A.M.; Vennema, H.; Rottier, P.J.M. Assembly of the coronavirus envelope: homotypic interactions between the M proteins. J. Virol., 2000, 74(11), 4967-4978.
[http://dx.doi.org/10.1128/JVI.74.11.4967-4978.2000] [PMID: 10799570]
[129]
Arndt, A.L.; Larson, B.J.; Hogue, B.G. A conserved domain in the coronavirus membrane protein tail is important for virus assembly. J. Virol., 2010, 84(21), 11418-11428.
[http://dx.doi.org/10.1128/JVI.01131-10] [PMID: 20719948]
[130]
Tseng, Y.T.; Chang, C.H.; Wang, S.M.; Huang, K.J.; Wang, C.T. Identifying SARS-CoV membrane protein amino acid residues linked to virus-like particle assembly. PLoS One, 2013, 8(5), e64013.
[http://dx.doi.org/10.1371/journal.pone.0064013] [PMID: 23700447]
[131]
Cao, Y.; Yang, R.; Wang, W.; Jiang, S.; Yang, C.; Liu, N.; Dai, H.; Lee, I.; Meng, X.; Yuan, Z. Probing the formation, structure and free energy relationships of M protein dimers of SARS-CoV-2. Comput. Struct. Biotechnol. J., 2022, 20, 573-582.
[http://dx.doi.org/10.1016/j.csbj.2022.01.007] [PMID: 35047128]
[132]
Wong, N.A.; Saier, M.H., Jr The SARS-coronavirus infection cycle: A survey of viral membrane proteins, their functional interactions and pathogenesis. Int. J. Mol. Sci., 2021, 22(3), 1308.
[http://dx.doi.org/10.3390/ijms22031308] [PMID: 33525632]
[133]
Hassan, S.S.; Choudhury, P.P.; Basu, P.; Jana, S.S. Molecular conservation and differential mutation on ORF3a gene in Indian SARS-CoV2 genomes. Genomics, 2020, 112(5), 3226-3237.
[http://dx.doi.org/10.1016/j.ygeno.2020.06.016] [PMID: 32540495]
[134]
Kern, D.M.; Sorum, B.; Mali, S.S.; Hoel, C.M.; Sridharan, S.; Remis, J.P.; Toso, D.B.; Kotecha, A.; Bautista, D.M.; Brohawn, S.G. Cryo-EM structure of SARS-CoV-2 ORF3a in lipid nanodiscs. Nat. Struct. Mol. Biol., 2021, 28(7), 573-582.
[http://dx.doi.org/10.1038/s41594-021-00619-0] [PMID: 34158638]
[135]
Issa, E.; Merhi, G.; Panossian, B.; Salloum, T.; Tokajian, S. SARS-CoV-2 and ORF3a: Nonsynonymous mutations, functional domains, and viral pathogenesis. mSystems, 2020, 5(3), e00266-e20.
[http://dx.doi.org/10.1128/mSystems.00266-20] [PMID: 32371472]
[136]
Ren, Y.; Shu, T.; Wu, D.; Mu, J.; Wang, C.; Huang, M.; Han, Y.; Zhang, X.Y.; Zhou, W.; Qiu, Y.; Zhou, X. The ORF3a protein of SARS-CoV-2 induces apoptosis in cells. Cell. Mol. Immunol., 2020, 17(8), 881-883.
[http://dx.doi.org/10.1038/s41423-020-0485-9] [PMID: 32555321]
[137]
Yue, Y.; Nabar, N.R.; Shi, C.S.; Kamenyeva, O.; Xiao, X.; Hwang, I.Y.; Wang, M.; Kehrl, J.H. SARS-coronavirus open reading Frame-3a drives multimodal necrotic cell death. Cell Death Dis., 2018, 9(9), 904.
[http://dx.doi.org/10.1038/s41419-018-0917-y] [PMID: 30185776]
[138]
Gunalan, V.; Mirazimi, A.; Tan, Y.J. A putative diacidic motif in the SARS-CoV ORF6 protein influences its subcellular localization and suppression of expression of co-transfected expression constructs. BMC Res. Notes, 2011, 4(1), 446.
[http://dx.doi.org/10.1186/1756-0500-4-446] [PMID: 22026976]
[139]
Li, J.Y.; Liao, C.H.; Wang, Q.; Tan, Y.J.; Luo, R.; Qiu, Y.; Ge, X.Y. The ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 inhibit type I interferon signaling pathway. Virus Res., 2020, 286, 198074.
[http://dx.doi.org/10.1016/j.virusres.2020.198074] [PMID: 32589897]
[140]
Morante, S.; La Penna, G.; Rossi, G.; Stellato, F. SARS-CoV-2 virion stabilization by Zn binding. Front. Mol. Biosci., 2020, 7, 222.
[http://dx.doi.org/10.3389/fmolb.2020.00222] [PMID: 33195401]
[141]
Lei, X.; Dong, X.; Ma, R.; Wang, W.; Xiao, X.; Tian, Z.; Wang, C.; Wang, Y.; Li, L.; Ren, L.; Guo, F.; Zhao, Z.; Zhou, Z.; Xiang, Z.; Wang, J. Activation and evasion of type I interferon responses by SARS-CoV-2. Nat. Commun., 2020, 11(1), 3810.
[http://dx.doi.org/10.1038/s41467-020-17665-9] [PMID: 32733001]
[142]
Xia, H.; Cao, Z.; Xie, X.; Zhang, X.; Chen, J.Y.C.; Wang, H.; Menachery, V.D.; Rajsbaum, R.; Shi, P.Y. Evasion of Type I interferon by SARS-CoV-2. Cell Rep., 2020, 33(1), 108234.
[http://dx.doi.org/10.1016/j.celrep.2020.108234] [PMID: 32979938]
[143]
Holland, L.A.; Kaelin, E.A.; Maqsood, R.; Estifanos, B.; Wu, L.I.; Varsani, A.; Halden, R.U.; Hogue, B.G.; Scotch, M.; Lim, E.S. An 81-nucleotide deletion in SARS-CoV-2 ORF7a identified from sentinel surveillance in Arizona (January to March 2020). J. Virol., 2020, 94(14), e00711-e00720.
[http://dx.doi.org/10.1128/JVI.00711-20] [PMID: 32357959]
[144]
Giri, R.; Bhardwaj, T.; Shegane, M.; Gehi, B.R.; Kumar, P.; Gadhave, K.; Oldfield, C.J.; Uversky, V.N. Understanding COVID-19 via comparative analysis of dark proteomes of SARS-CoV-2, human SARS and bat SARS-like coronaviruses. Cell. Mol. Life Sci., 2021, 78(4), 1655-1688.
[http://dx.doi.org/10.1007/s00018-020-03603-x] [PMID: 32712910]
[145]
Ostaszewski, M.; Mazein, A.; Gillespie, M.E.; Kuperstein, I.; Niarakis, A.; Hermjakob, H.; Pico, A.R.; Willighagen, E.L.; Evelo, C.T.; Hasenauer, J.; Schreiber, F.; Dräger, A.; Demir, E.; Wolkenhauer, O.; Furlong, L.I.; Barillot, E.; Dopazo, J.; Orta-Resendiz, A.; Messina, F.; Valencia, A.; Funahashi, A.; Kitano, H.; Auffray, C.; Balling, R.; Schneider, R. COVID-19 Disease Map, building a computational repository of SARS-CoV-2 virus-host interaction mechanisms. Sci. Data, 2020, 7(1), 136.
[http://dx.doi.org/10.1038/s41597-020-0477-8] [PMID: 32371892]
[146]
Zhang, Y.; Chen, Y.; Li, Y.; Huang, F.; Luo, B.; Yuan, Y.; Xia, B.; Ma, X.; Yang, T.; Yu, F.; Liu, J.; Liu, B.; Song, Z.; Chen, J.; Yan, S.; Wu, L.; Pan, T.; Zhang, X.; Li, R.; Huang, W.; He, X.; Xiao, F.; Zhang, J.; Zhang, H. The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-regulating MHC-. Proc. Natl. Acad. Sci. USA, 2021, 118(23), e2024202118.
[http://dx.doi.org/10.1073/pnas.2024202118] [PMID: 34021074]
[147]
Hassan, S.S.; Aljabali, A.A.A.; Panda, P.K.; Ghosh, S.; Attrish, D.; Choudhury, P.P.; Seyran, M.; Pizzol, D.; Adadi, P.; Abd El-Aziz, T.M.; Soares, A.; Kandimalla, R.; Lundstrom, K.; Lal, A.; Azad, G.K.; Uversky, V.N.; Sherchan, S.P.; Baetas-da-Cruz, W.; Uhal, B.D.; Rezaei, N.; Chauhan, G.; Barh, D.; Redwan, E.M.; Dayhoff, G.W., II; Bazan, N.G.; Serrano-Aroca, Á.; El-Demerdash, A.; Mishra, Y.K.; Palu, G.; Takayama, K.; Brufsky, A.M.; Tambuwala, M.M. A unique view of SARS-CoV-2 through the lens of ORF8 protein. Comput. Biol. Med., 2021, 133, 104380.
[http://dx.doi.org/10.1016/j.compbiomed.2021.104380] [PMID: 33872970]
[148]
Hassan, S.S.; Attrish, D.; Ghosh, S.; Choudhury, P.P.; Uversky, V.N.; Aljabali, A.A.A.; Lundstrom, K.; Uhal, B.D.; Rezaei, N.; Seyran, M.; Pizzol, D.; Adadi, P.; Soares, A.; Abd El-Aziz, T.M.; Kandimalla, R.; Tambuwala, M.M.; Azad, G.K.; Sherchan, S.P.; Baetas-da-Cruz, W.; Lal, A.; Palù, G.; Takayama, K.; Serrano-Aroca, Á.; Barh, D.; Brufsky, A.M. Notable sequence homology of the ORF10 protein introspects the architecture of SARS-CoV-2. Int. J. Biol. Macromol., 2021, 181, 801-809.
[http://dx.doi.org/10.1016/j.ijbiomac.2021.03.199] [PMID: 33862077]
[149]
Rosales, P.F.; Bordin, G.S.; Gower, A.E.; Moura, S. Indole alkaloids: 2012 until now, highlighting the new chemical structures and biological activities. Fitoterapia, 2020, 143, 104558.
[http://dx.doi.org/10.1016/j.fitote.2020.104558] [PMID: 32198108]
[150]
Babbar, N. An introduction to alkaloids and their applications in pharmaceutical chemistry. Pharma Innovation Journal, 2015, 4(10), 74-75.
[151]
He, C.L.; Huang, L.Y.; Wang, K.; Gu, C.J.; Hu, J.; Zhang, G.J.; Xu, W.; Xie, Y.H.; Tang, N.; Huang, A.L. Identification of bis-benzylisoquinoline alkaloids as SARS-CoV-2 entry inhibitors from a library of natural products. Signal Transduct. Target. Ther., 2021, 6(1), 131.
[http://dx.doi.org/10.1038/s41392-021-00531-5] [PMID: 33758167]
[152]
Daniloski, Z.; Jordan, T.X.; Wessels, H.H.; Hoagland, D.A.; Kasela, S.; Legut, M.; Maniatis, S.; Mimitou, E.P.; Lu, L.; Geller, E.; Danziger, O.; Rosenberg, B.R.; Phatnani, H.; Smibert, P.; Lappalainen, T.; tenOever, B.R.; Sanjana, N.E. Identification of required host factors for SARS-CoV-2 infection in human cells. Cell, 2021, 184(1), 92-105.e16.
[http://dx.doi.org/10.1016/j.cell.2020.10.030] [PMID: 33147445]
[153]
Hijikata, A.; Shionyu-Mitsuyama, C.; Nakae, S.; Shionyu, M.; Ota, M.; Kanaya, S.; Hirokawa, T.; Nakajima, S.; Watashi, K.; Shirai, T. Evaluating cepharanthine analogues as natural drugs against SARS‐CoV‐2. FEBS Open Bio, 2022, 12(1), 285-294.
[http://dx.doi.org/10.1002/2211-5463.13337] [PMID: 34850606]
[154]
Marahatha, R.; Shrestha, A.; Sharma, K.; Regmi, B.P.; Sharma, K.R.; Poudel, P.; Basnyat, R.C.; Parajuli, N. In silico study of alkaloids: Neferine and Berbamine potentially inhibit the SARS-CoV-2 RNA-Dependent RNA Polymerase J. Chem, 2022, 2022
[http://dx.doi.org/10.1155/2022/7548802]
[155]
Aranda, J.; Wieczór, M.; Terrazas, M.; Brun-Heath, I.; Orozco, M. Mechanism of reaction of RNA-dependent RNA polymerase from SARS-CoV-2. Chem Catalysis, 2022, 2(5), 1084-1099.
[http://dx.doi.org/10.1016/j.checat.2022.03.019] [PMID: 35465139]
[156]
a) Kumar, R.; Afsar, M.; Khandelwal, N.; Chander, Y.; Riyesh, T.; Dedar, R.K.; Gulati, B.R.; Pal, Y.; Barua, S.; Tripathi, B.N.; Hussain, T.; Kumar, N. Emetine suppresses SARS-CoV-2 replication by inhibiting interaction of viral mRNA with eIF4E. Antiviral Res., 2021, 189, 105056.
[http://dx.doi.org/10.1016/j.antiviral.2021.105056];
b) Wang, A.; Sun, Y.; Liu, Q.; Wu, H.; Liu, J.; He, J.; Yu, J.; Chen, Q.Q.; Ge, Y.; Zhang, Z.; Hu, C.; Chen, C.; Qi, Z.; Zou, F.; Liu, F.; Hu, J.; Zhao, M.; Huang, T.; Wang, B.; Wang, L.; Wang, W.; Wang, W.; Ren, T.; Liu, J.; Sun, Y.; Fan, S.; Wu, Q.; Liang, C.; Sun, L.; Su, B.; Wei, W.; Liu, Q. Low dose of emetine as potential anti-SARS-CoV-2 virus therapy: preclinical in vitro inhibition and in vivo pharmacokinetic evidences. Molecular Biomedicine, 2020, 1(1), 14.
[http://dx.doi.org/10.1186/s43556-020-00018-9] [PMID: 34765997]
[157]
Choy, K.T.; Wong, A.Y.L.; Kaewpreedee, P.; Sia, S.F.; Chen, D.; Hui, K.P.Y.; Chu, D.K.W.; Chan, M.C.W.; Cheung, P.P.H.; Huang, X.; Peiris, M.; Yen, H.L. Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro. Antiviral Res., 2020, 178, 104786.
[http://dx.doi.org/10.1016/j.antiviral.2020.104786] [PMID: 32251767]
[158]
Isah, M.B.; Tajuddeen, N.; Umar, M.I.; Alhafiz, Z.A.; Mohammed, A.; Ibrahim, M.A. Terpenoids as emerging therapeutic agents: Cellular targets and mechanisms of action against protozoan parasites. Studies Nat. Prod. Chem., 2018, 59, 227-250.
[http://dx.doi.org/10.1016/B978-0-444-64179-3.00007-4]
[159]
Ludwiczuk, A.; Skalicka-Woźniak, K.; Georgiev, M.I. Terpenoids. In: Pharmacognosy: Fundamentals, Applications and Strategies; Elsevier, 2017; pp. 233-266.
[160]
Mbaveng, A.T.; Hamm, R.; Kuete, V. Harmful and protective effects of terpenoids from African medicinal plants. In: Toxicological Survey of African Medicinal Plants; Elsevier, 2014; pp. 557-576.
[http://dx.doi.org/10.1016/B978-0-12-800018-2.00019-4]
[161]
Li, X.; Gao, J.; Li, M.; Cui, H.; Jiang, W.; Tu, Z.; Yuan, T. Aromatic cadinane sesquiterpenoids from the fruiting bodies of Phellinus pini block SARS-CoV-2 spike-ACE2 interaction. J. Nat. Prod., 2021, 84(8), 2385-2389.
[http://dx.doi.org/10.1021/acs.jnatprod.1c00426] [PMID: 34351742]
[162]
Sa-ngiamsuntorn, K.; Suksatu, A.; Pewkliang, Y.; Thongsri, P.; Kanjanasirirat, P.; Manopwisedjaroen, S.; Charoensutthivarakul, S.; Wongtrakoongate, P.; Pitiporn, S.; Chaopreecha, J.; Kongsomros, S.; Jearawuttanakul, K.; Wannalo, W.; Khemawoot, P.; Chutipongtanate, S.; Borwornpinyo, S.; Thitithanyanont, A.; Hongeng, S. Anti-SARS-CoV-2 activity of Andrographis paniculata extract and its major component andrographolide in human lung epithelial cells and cytotoxicity evaluation in major organ cell representatives. J. Nat. Prod., 2021, 84(4), 1261-1270.
[http://dx.doi.org/10.1021/acs.jnatprod.0c01324] [PMID: 33844528]
[163]
Elebeedy, D.; Elkhatib, W.F.; Kandeil, A.; Ghanem, A.; Kutkat, O.; Alnajjar, R.; Saleh, M.A.; Abd El Maksoud, A.I.; Badawy, I.; Al-Karmalawy, A.A. Anti-SARS-CoV-2 activities of tanshinone IIA, carnosic acid, rosmarinic acid, salvianolic acid, baicalein, and glycyrrhetinic acid between computational and in vitro insights. RSC Advances, 2021, 11(47), 29267-29286.
[http://dx.doi.org/10.1039/D1RA05268C] [PMID: 35492070]
[164]
Kanjanasirirat, P.; Suksatu, A.; Manopwisedjaroen, S.; Munyoo, B.; Tuchinda, P.; Jearawuttanakul, K.; Seemakhan, S.; Charoensutthivarakul, S.; Wongtrakoongate, P.; Rangkasenee, N.; Pitiporn, S.; Waranuch, N.; Chabang, N.; Khemawoot, P.; Sa-ngiamsuntorn, K.; Pewkliang, Y.; Thongsri, P.; Chutipongtanate, S.; Hongeng, S.; Borwornpinyo, S.; Thitithanyanont, A. High-content screening of Thai medicinal plants reveals Boesenbergia rotunda extract and its component Panduratin A as anti-SARS-CoV-2 agents. Sci. Rep., 2020, 10(1), 19963.
[http://dx.doi.org/10.1038/s41598-020-77003-3] [PMID: 33203926]
[165]
Yi, Y.; Li, J.; Lai, X.; Zhang, M.; Kuang, Y.; Bao, Y.O.; Yu, R.; Hong, W.; Muturi, E.; Xue, H.; Wei, H.; Li, T.; Zhuang, H.; Qiao, X.; Xiang, K.; Yang, H.; Ye, M. Natural triterpenoids from licorice potently inhibit SARS-CoV-2 infection. J. Adv. Res., 2022, 36, 201-210.
[http://dx.doi.org/10.1016/j.jare.2021.11.012] [PMID: 35116174]
[166]
Gowda, P.; Patrick, S.; Joshi, S.D.; Kumawat, R.K.; Sen, E. Glycyrrhizin prevents SARS-CoV-2 S1 and Orf3a induced high mobility group box 1 (HMGB1) release and inhibits viral replication. Cytokine, 2021, 142, 155496.
[http://dx.doi.org/10.1016/j.cyto.2021.155496] [PMID: 33773396]
[167]
Xiong, Y.; Zhu, G.H.; Wang, H.N.; Hu, Q.; Chen, L.L.; Guan, X.Q.; Li, H.L.; Chen, H.Z.; Tang, H.; Ge, G.B. Discovery of naturally occurring inhibitors against SARS-CoV-2 3CLpro from Ginkgo biloba leaves via large-scale screening. Fitoterapia, 2021, 152, 104909.
[http://dx.doi.org/10.1016/j.fitote.2021.104909] [PMID: 33894315]
[168]
Panche, A.N.; Diwan, A.D.; Chandra, S.R. Flavonoids: an overview. J. Nutr. Sci., 2016, 5, e47.
[http://dx.doi.org/10.1017/jns.2016.41] [PMID: 28620474]
[169]
Nguyen, T.T.H.; Jung, J.H.; Kim, M.K.; Lim, S.; Choi, J.M.; Chung, B.; Kim, D.W.; Kim, D. The inhibitory effects of plant derivate polyphenols on the main protease of SARS coronavirus 2 and their structure-activity relationship. Molecules, 2021, 26(7), 1924.
[http://dx.doi.org/10.3390/molecules26071924] [PMID: 33808054]
[170]
Hong, S.; Seo, S.H.; Woo, S.J.; Kwon, Y.; Song, M.; Ha, N.C. Epigallocatechin gallate inhibits the uridylate-specific endoribonuclease Nsp15 and efficiently neutralizes the SARS-CoV-2 strain. J. Agric. Food Chem., 2021, 69(21), 5948-5954.
[http://dx.doi.org/10.1021/acs.jafc.1c02050] [PMID: 34015930]
[171]
Pillon, M.C.; Frazier, M.N.; Dillard, L.B.; Williams, J.G.; Kocaman, S.; Krahn, J.M.; Perera, L.; Hayne, C.K.; Gordon, J.; Stewart, Z.D.; Sobhany, M.; Deterding, L.J.; Hsu, A.L.; Dandey, V.P.; Borgnia, M.J.; Stanley, R.E. Cryo-EM structures of the SARS-CoV-2 endoribonuclease Nsp15 reveal insight into nuclease specificity and dynamics. Nat. Commun., 2021, 12(1), 636.
[http://dx.doi.org/10.1038/s41467-020-20608-z] [PMID: 33504779]
[172]
Su, H.; Yao, S.; Zhao, W.; Li, M.; Liu, J.; Shang, W.; Xie, H.; Ke, C.; Hu, H.; Gao, M.; Yu, K.; Liu, H.; Shen, J.; Tang, W.; Zhang, L.; Xiao, G.; Ni, L.; Wang, D.; Zuo, J.; Jiang, H.; Bai, F.; Wu, Y.; Ye, Y.; Xu, Y. Anti-SARS-CoV-2 activities in vitro of Shuanghuanglian preparations and bioactive ingredients. Acta Pharmacol. Sin., 2020, 41(9), 1167-1177.
[http://dx.doi.org/10.1038/s41401-020-0483-6] [PMID: 32737471]
[173]
Du, A.; Zheng, R.; Disoma, C.; Li, S.; Chen, Z.; Li, S.; Liu, P.; Zhou, Y.; Shen, Y.; Liu, S.; Zhang, Y.; Dong, Z.; Yang, Q.; Alsaadawe, M.; Razzaq, A.; Peng, Y.; Chen, X.; Hu, L.; Peng, J.; Zhang, Q.; Jiang, T.; Mo, L.; Li, S.; Xia, Z. Epigallocatechin-3-gallate, an active ingredient of traditional chinese medicines, inhibits the 3CLpro activity of SARS-CoV-2. Int. J. Biol. Macromol., 2021, 176, 1-12.
[http://dx.doi.org/10.1016/j.ijbiomac.2021.02.012] [PMID: 33548314]
[174]
Xiong, Y.; Zhu, G.H.; Zhang, Y.N.; Hu, Q.; Wang, H.N.; Yu, H.N.; Qin, X.Y.; Guan, X.Q.; Xiang, Y.W.; Tang, H.; Ge, G.B. Flavonoids in Ampelopsis grossedentata as covalent inhibitors of SARS-CoV-2 3CLpro: Inhibition potentials, covalent binding sites and inhibitory mechanisms. Int. J. Biol. Macromol., 2021, 187, 976-987.
[http://dx.doi.org/10.1016/j.ijbiomac.2021.07.167] [PMID: 34333006]
[175]
Abian, O.; Ortega-Alarcon, D.; Jimenez-Alesanco, A.; Ceballos-Laita, L.; Vega, S.; Reyburn, H.T.; Rizzuti, B.; Velazquez-Campoy, A. Structural stability of SARS-CoV-2 3CLpro and identification of quercetin as an inhibitor by experimental screening. Int. J. Biol. Macromol., 2020, 164, 1693-1703.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.07.235] [PMID: 32745548]
[176]
Bahun, M.; Jukić, M.; Oblak, D.; Kranjc, L.; Bajc, G.; Butala, M.; Bozovičar, K.; Bratkovič, T.; Podlipnik, Č.; Poklar Ulrih, N. Inhibition of the SARS-CoV-2 3CLpro main protease by plant polyphenols. Food Chem.,, 2022, 373(Pt B), 131594.
[http://dx.doi.org/10.1016/j.foodchem.2021.131594] [PMID: 34838409]
[177]
Kato, Y.; Higashiyama, A.; Takaoka, E.; Nishikawa, M.; Ikushiro, S. Food phytochemicals, epigallocatechin gallate and myricetin, covalently bind to the active site of the coronavirus main protease in vitro. Advances in Redox Research, 2021, 3, 100021.
[http://dx.doi.org/10.1016/j.arres.2021.100021] [PMID: 35425933]
[178]
Su, H.; Yao, S.; Zhao, W.; Li, M.; Liu, J.; Shang, W.; Xie, H.; Ke, C.; Gao, M.; Yu, K.; Liu, H.; Shen, J.; Tang, W.; Zhang, L.; Zuo, J.; Jiang, H.; Bai, F.; Wu, Y.; Ye, Y.; Xu, Y. Discovery of baicalin and baicalein as novel, natural product inhibitors of SARS-CoV-2 3CL protease in vitro. bioRxiv, 2020.
[http://dx.doi.org/10.1101/2020.04.13.038687]
[179]
Su, H.; Yao, S.; Zhao, W.; Zhang, Y.; Liu, J.; Shao, Q.; Wang, Q.; Li, M.; Xie, H.; Shang, W.; Ke, C.; Feng, L.; Jiang, X.; Shen, J.; Xiao, G.; Jiang, H.; Zhang, L.; Ye, Y.; Xu, Y. Identification of pyrogallol as a warhead in design of covalent inhibitors for the SARS-CoV-2 3CL protease. Nat. Commun., 2021, 12(1), 3623.
[http://dx.doi.org/10.1038/s41467-021-23751-3] [PMID: 34131140]
[180]
Li, L.; Ma, L.; Hu, Y.; Li, X.; Yu, M.; Shang, H.; Zou, Z. Natural biflavones are potent inhibitors against SARS-CoV-2 papain-like protease. Phytochemistry, 2022, 193, 112984.
[http://dx.doi.org/10.1016/j.phytochem.2021.112984] [PMID: 34757253]
[181]
Kim, J.S.; Kang, O.J.; Gweon, O.C. Comparison of phenolic acids and flavonoids in black garlic at different thermal processing steps. J. Funct. Foods, 2013, 5(1), 80-86.
[http://dx.doi.org/10.1016/j.jff.2012.08.006]
[182]
Liu, S.Y.; Wang, W.; Ke, J.P.; Zhang, P.; Chu, G.X.; Bao, G.H. Discovery of Camellia sinensis catechins as SARS-CoV-2 3CL protease inhibitors through molecular docking, intra and extra cellular assays. Phytomedicine, 2022, 96, 153853.
[http://dx.doi.org/10.1016/j.phymed.2021.153853] [PMID: 34799184]
[183]
Pandey, K.B.; Rizvi, S.I. Plant polyphenols as dietary antioxidants in human health and disease. Oxid. Med. Cell. Longev., 2009, 2(5), 270-278.
[http://dx.doi.org/10.4161/oxim.2.5.9498] [PMID: 20716914]
[184]
Du, R.; Cooper, L.; Chen, Z.; Lee, H.; Rong, L.; Cui, Q. Discovery of chebulagic acid and punicalagin as novel allosteric inhibitors of SARS-CoV-2 3CLpro. Antiviral Res., 2021, 190, 105075.
[http://dx.doi.org/10.1016/j.antiviral.2021.105075] [PMID: 33872675]
[185]
Yang, M.; Wei, J.; Huang, T.; Lei, L.; Shen, C.; Lai, J.; Yang, M.; Liu, L.; Yang, Y.; Liu, G.; Liu, Y. Resveratrol inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS‐COV ‐2) in cultured Vero cells. Phytother. Res., 2021, 35(3), 1127-1129.
[http://dx.doi.org/10.1002/ptr.6916] [PMID: 33222316]
[186]
Gangadevi, S.; Badavath, V.N.; Thakur, A.; Yin, N.; De Jonghe, S.; Acevedo, O.; Jochmans, D.; Leyssen, P.; Wang, K.; Neyts, J.; Yujie, T.; Blum, G. Kobophenol A inhibits binding of host ACE2 receptor with spike RBD domain of SARS-CoV-2, a lead compound for blocking COVID-19. J. Phys. Chem. Lett., 2021, 12(7), 1793-1802.
[http://dx.doi.org/10.1021/acs.jpclett.0c03119] [PMID: 33577324]
[187]
Dhanjal, J.K.; Kumar, V.; Garg, S.; Subramani, C.; Agarwal, S.; Wang, J.; Zhang, H.; Kaul, A.; Kalra, R.S.; Kaul, S.C.; Vrati, S.; Sundar, D.; Wadhwa, R. Molecular mechanism of anti-SARS-CoV2 activity of Ashwagandha-derived withanolides. Int. J. Biol. Macromol., 2021, 184, 297-312.
[http://dx.doi.org/10.1016/j.ijbiomac.2021.06.015] [PMID: 34118289]
[188]
Martínez, M.J.A.; Benito, P.B. Biological activity of quinones. In: Studies in Natural Products Chemistry; , 2005; 30, pp. 303-366.
[http://dx.doi.org/10.1016/S1572-5995(05)80036-5]
[189]
Cui, J.; Jia, J. Discovery of juglone and its derivatives as potent SARS-CoV-2 main proteinase inhibitors. Eur. J. Med. Chem., 2021, 225, 113789.
[http://dx.doi.org/10.1016/j.ejmech.2021.113789] [PMID: 34438124]
[190]
Li, Y.T.; Yang, C.; Wu, Y.; Lv, J.J.; Feng, X.; Tian, X.; Zhou, Z.; Pan, X.; Liu, S.; Tian, L.W. Axial chiral binaphthoquinone and perylenequinones from the stromata of Hypocrella bambusae are SARS-CoV-2 entry inhibitors. J. Nat. Prod., 2021, 84(2), 436-443.
[http://dx.doi.org/10.1021/acs.jnatprod.0c01136] [PMID: 33560122]
[191]
Raj, V.; Park, J.G.; Cho, K.H.; Choi, P.; Kim, T.; Ham, J.; Lee, J. Assessment of antiviral potencies of cannabinoids against SARS-CoV-2 using computational and in vitro approaches. Int. J. Biol. Macromol., 2021, 168, 474-485.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.12.020] [PMID: 33290767]
[192]
Prieto, M.A.; López, C.J.; Simal-Gandara, J. Glucosinolates: Molecular structure, breakdown, genetic, bioavailability, properties and healthy and adverse effects. Adv. Food Nutr. Res., 2019, 90, 305-350.
[http://dx.doi.org/10.1016/bs.afnr.2019.02.008] [PMID: 31445598]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy