Targeting Natural Products for the Treatment of COVID-19 – An Updated Review

Author(s): Ramachandra R. Pamuru, Naveen Ponneri, Amooru G. Damu, Ramakrishna Vadde*

Journal Name: Current Pharmaceutical Design

Volume 26 , Issue 41 , 2020


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Abstract:

Background: Coronavirus disease 2019 (COVID-19) is an ongoing, rapidly spreading pandemic caused by Severe Acute Respiratory Syndrome Coronavirus2 (SARS-CoV2). Among all the infected countries around the globe as of now (June 15, 2020), the total confirmed positive cases reported are 7,805,148, with the death of 431,192. At present, no specialized treatments evolved to cure COVID-19. Its treatment is symptomatic. Though huge efforts are being made to produce potential therapies to scuffle COVID-19, no drug has been discovered so far.

Objective: Natural products have been playing a significant role in disease control since ancient days. These products serve as templates for designing new anti-microbial agents with a different mechanism of action and also open a door for investigation of effective anti-viral drugs to combat COVID-19. By focusing on this, the authors have narrated the basic structure, infection, and pathogenesis of SARS-CoV2 virus in humans and also reported various natural products or plant-based extracts/bioactive compounds tested against coronaviruses like SARS and MERS, as these viruses are structurally similar to SARS-CoV2 and can be used in designing novel drug against this virus.

Conclusion: The natural products having the potential to combat SARS, MERS, and other viruses reviewed in this review article might have anti-viral activities against the SARS-CoV2 virus and can be used directly for further preclinical studies. Therefore, all efforts should be focused on overcoming this serious problem to save many people's lives all over the world.

Keywords: COVID-19, SARS-CoV2, pathogenesis, natural products, anti-viral property, therapy.

[1]
Wu JT, Leung K, Leung GM. Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study. Lancet 2020; 395(10225): 689-97.[http://dx.doi.org/10.1016/S0140-6736(20)30260-9] [PMID: 32014114]
[2]
Huang C, Wang Y, Li X, et al. 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]
[3]
Gorbalenya AE, Baker SC, Baric RS, et al. Severe acute respiratory syndrome-related coronavirus: the species and its viruses-a statement of the Coronavirus Study Group. bioRxiv 2020.[http://dx.doi.org/10.1101/2020.02.07.937862]
[4]
de Wit E, van Doremalen N, Falzarano D, et al. SARS and MERS: recent insightsinto emerging coronaviruses Nat Rev Microbiol 2016.[http://dx.doi.org/10.1038/nrmicro.2016.81]
[5]
Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579(7798): 270-3.[http://dx.doi.org/10.1038/s41586-020-2012-7] [PMID: 32015507]
[6]
Li X, Geng M, Peng Y, Meng L, Lu S. Molecular immune pathogenesis and diagnosis of COVID-19. J Pharm Anal 2020; 10(2): 102-8.[http://dx.doi.org/10.1016/j.jpha.2020.03.001] [PMID: 32282863]
[7]
Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro Cell Res 2020; 30: 269-71.
[8]
Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res 2020; 178: 104787.[http://dx.doi.org/10.1016/j.antiviral.2020.104787] [PMID: 32251768]
[9]
Tian X, Li C, Huang A, et al. Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody. Emerg Microb Infect 2020; 9: 382-5.[http://dx.doi.org/10.1080/22221751.2020.1729069]
[10]
Zhang L, Liu Y. Potential interventions for novel coronavirus in China: A systematic review. J Med Virol 2020; 92(5): 479-90.[http://dx.doi.org/10.1002/jmv.25707] [PMID: 32052466]
[11]
Yan R, Zhang Y, Li Y, et al. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2 Science 2020; 367(6485): 1444-8.
[12]
Gupta MK, Vemula S, Donde R, Gouda G, Behera L, Vadde R. In-silico approaches to detect inhibitors of the human severe acute respiratory syndrome coronavirus envelope protein ion channel. J Biomol Struct Dyn 2020; 1-11.[http://dx.doi.org/10.1080/07391102.2020.1751300] [PMID: 32238078]
[13]
Lai MM, Cavanagh D. The molecular biology of coronaviruses. Adv Virus Res 1997; 48: 1-100.[http://dx.doi.org/10.1016/S0065-3527(08)60286-9] [PMID: 9233431]
[14]
Elfiky AA. Natural products may interfere with SARS-CoV-2 attachment to the host cell. J Biomol Struct Dyn 2020; : 1-10.[http://dx.doi.org/10.1080/07391102.2020.1761881] [PMID: 32340551]
[15]
Rahman N, Basharat Z, Yousuf M, Castaldo G, Rastrelli L, Khan H. Virtual Screening of Natural Products against Type II Transmembrane Serine Protease (TMPRSS2), the Priming Agent of Coronavirus 2 (SARS-CoV-2). Molecules 2020; 25(10): 2271.[http://dx.doi.org/10.3390/molecules25102271] [PMID: 32408547]
[16]
Su S, Wong G, Shi W, et al. Epidemiology, Genetic recombination, and pathogenesis of coronaviruses Trends Microbiol 2016; 24: 490-502.
[17]
Fouchier RA, Hartwig NG, Bestebroer TM, et al. A previously undescribed coronavirus associated with respiratory disease in humans. Proc Natl Acad Sci USA 2004; 101(16): 6212-6.[http://dx.doi.org/10.1073/pnas.0400762101] [PMID: 15073334]
[18]
van der Hoek L, Pyrc K, Jebbink MF, et al. Identification of a new human coronavirus. Nat Med 2004; 10(4): 368-73.[http://dx.doi.org/10.1038/nm1024] [PMID: 15034574]
[19]
Hasoksuz M, Alekseev K, Vlasova A, et al. Biologic, antigenic, and full-length genomic characterization of a bovine-like coronavirus isolated from a giraffe. J Virol 2007; 81(10): 4981-90.[http://dx.doi.org/10.1128/JVI.02361-06] [PMID: 17344285]
[20]
Woo PC, Lau SKP, Yip CCY, et al. Comparative analysis of 22 coronavirus HKU1 genomes reveals a novel genotype and evidence of natural recombination in coronavirus HKU1. J Virol 2006; 80(14): 7136-45.[http://dx.doi.org/10.1128/JVI.00509-06] [PMID: 16809319]
[21]
Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020; 395(10223): 507-13.[http://dx.doi.org/10.1016/S0140-6736(20)30211-7] [PMID: 32007143]
[22]
Wu C, Liu Y, Yang Y, et al. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm Sin B 2020; 10: 766-88.[http://dx.doi.org/10.1016/j.apsb.2020.02.008] [PMID: 32292689]
[23]
Xu X, Chen P, Wang J, et al. 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): 457-60.[http://dx.doi.org/10.1007/s11427-020-1637-5] [PMID: 32009228]
[24]
El Sahly HM. Genomic Characterization of the 2019 Novel Coronavirus. N Engl J Med 2020; 2020(February)https://www.jwatch.org/na50823/2020/02/06/genomic-characterization-2019-novel-coronavirus
[25]
Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature 2020; 579(7798): 265-9.[http://dx.doi.org/10.1038/s41586-020-2008-3] [PMID: 32015508]
[26]
Song Z, Xu Y, Bao L, et al. From SARS to MERS, thrusting coronaviruses into the spotlight. Viruses 2019; 11(1): E59.[http://dx.doi.org/10.3390/v11010059] [PMID: 30646565]
[27]
Peiris JS, Guan Y, Yuen KY. Severe acute respiratory syndrome. Nat Med 2004; 10(12): S88-97.[http://dx.doi.org/10.1038/nm1143]
[28]
Cui J, Li F, Shi ZL. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol 2019; 17(3): 181-92.[http://dx.doi.org/10.1038/s41579-018-0118-9] [PMID: 30531947]
[29]
Wu A, Peng Y, Huang B, et al. Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China. Cell Host Microbe 2020; 27(3): 325-8.[http://dx.doi.org/10.1016/j.chom.2020.02.001] [PMID: 32035028]
[30]
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): 584-8.[http://dx.doi.org/10.1002/jmv.25719] [PMID: 32083328]
[31]
Zhang L, Shen FM, Chen F, Lin Z. Origin and evolution of the 2019 novel coronavirus. Clin Infect Dis 2020; 71(15): 882-3.[http://dx.doi.org/10.1093/cid/ciaa112] [PMID: 32011673]
[32]
Giovanetti M, Benvenuto D, Angeletti S, Ciccozzi M. The first two cases of 2019-nCoV in Italy: Where they come from? J Med Virol 2020; 92(5): 518-21.[http://dx.doi.org/10.1002/jmv.25699] [PMID: 32022275]
[33]
Paraskevis D, Kostaki EG, Magiorkinis G, Panayiotakopoulos G, Sourvinos G, Tsiodras S. Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event. Infect Genet Evol 2020; 79: 104212.[http://dx.doi.org/10.1016/j.meegid.2020.104212] [PMID: 32004758]
[34]
Hui KPY, Cheung MC, Perera RAPM, et al. Tropism, replication competence, and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: an analysis in ex-vivo and in-vitro cultures. Lancet Respir Med 2020; 8(7): 687-95.[http://dx.doi.org/10.1016/S2213-2600(20)30193-4] [PMID: 32386571]
[35]
Lin L, Lu L, Cao W, Li T. Hypothesis for potential pathogenesis of SARS-CoV-2 infection-a review of immune changes in patients with viral pneumonia. Emerg Microbes Infect 2020; 9(1): 727-32.[http://dx.doi.org/10.1080/22221751.2020.1746199] [PMID: 32196410]
[36]
de Wit E, van Doremalen N, Falzarano D, Munster VJ. SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol 2016; 14(8): 523-34.[http://dx.doi.org/10.1038/nrmicro.2016.81] [PMID: 27344959]
[37]
Hoffmann M, Kleine-Weber H, Schroeder S, et al. 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]
[38]
Millet JK, Whittaker GR. Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein. Proc Natl Acad Sci USA 2014; 111(42): 15214-9.[http://dx.doi.org/10.1073/pnas.1407087111] [PMID: 25288733]
[39]
Dan H, Maureen G, Richard B, et al. Quantitative mRNA expression pro¢ling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS 2002; 532: 107-10.[http://dx.doi.org/10.1016/S0014-5793(02)03640-2]
[40]
Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol 2020; 5(4): 562-9.[http://dx.doi.org/10.1038/s41564-020-0688-y] [PMID: 32094589]
[41]
Chen X, Zhao B, Qu Y, et al. Detectable Serum Severe Acute Respiratory Syndrome Coronavirus 2 Viral Load (RNAemia) Is Closely Correlated With Drastically Elevated Interleukin 6 Level in Critically Ill Patients With Coronavirus Disease 2019. Clin Infect Dis 2020.[http://dx.doi.org/10.1093/cid/ciaa449] [PMID: 32301997]
[42]
Wang K, Chen W, Zhou YS, et al. SARS-CoV-2 invades host cells via a novel route: CD147-spike protein. bioRxiv 2020.[http://dx.doi.org/10.1101/2020.03.14.988345]
[43]
Shanmugaraj B, Siriwattananon K, Wangkanont K, Phoolcharoen W. Perspectives on monoclonal antibody therapy as potential therapeutic intervention for Coronavirus disease-19 (COVID-19). Asian Pac J Allergy Immunol 2020; 38(1): 10-8.[PMID: 32134278]
[44]
Wen CC, Kuo YH, Jan JT, et al. Specific plant terpenoids and lignoids possess potent antiviral activities against severe acute respiratory syndrome coronavirus. J Med Chem 2007; 50(17): 4087-95.[http://dx.doi.org/10.1021/jm070295s] [PMID: 17663539]
[45]
Zhuang M, Jiang H, Suzuki Y, et al. Procyanidins and butanol extract of Cinnamomi Cortex inhibit SARS-CoV infection. Antiviral Res 2009; 82(1): 73-81.[http://dx.doi.org/10.1016/j.antiviral.2009.02.001] [PMID: 19428598]
[46]
Yang CW, Lee YZ, Kang IJ, et al. Identification of phenanthroindolizines and phenanthroquinolizidines as novel potent anti-coronaviral agents for porcine enteropathogenic coronavirus transmissible gastroenteritis virus and human severe acute respiratory syndrome coronavirus. Antiviral Res 2010; 88(2): 160-8.[http://dx.doi.org/10.1016/j.antiviral.2010.08.009] [PMID: 20727913]
[47]
Mitchell CA, Ramessar K, O’Keefe BR. Antiviral lectins: Selective inhibitors of viral entry. Antiviral Res 2017; 142: 37-54.[http://dx.doi.org/10.1016/j.antiviral.2017.03.007] [PMID: 28322922]
[48]
Ho TY, Wu SL, Chen JC, Li CC, Hsiang CY. Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction. Antiviral Res 2007; 74(2): 92-101.[http://dx.doi.org/10.1016/j.antiviral.2006.04.014] [PMID: 16730806]
[49]
Lau KM, Lee KM, Koon CM, et al. Immunomodulatory and anti-SARS activities of Houttuynia cordata. J Ethnopharmacol 2008; 118(1): 79-85.[http://dx.doi.org/10.1016/j.jep.2008.03.018] [PMID: 18479853]
[50]
Ulasli M, Gurses SA, Bayraktar R, et al. The effects of Nigella sativa (Ns), Anthemis hyalina (Ah) and Citrus sinensis (Cs) extracts on the replication of coronavirus and the expression of TRP genes family. Mol Biol Rep 2014; 41(3): 1703-11.[http://dx.doi.org/10.1007/s11033-014-3019-7] [PMID: 24413991]
[51]
Kim DE, Min JS, Jang MS, et al. Natural Bis-Benzylisoquinoline Alkaloids-Tetrandrine, Fangchinoline, and Cepharanthine, inhibit human Coronavirus OC43 infection of MRC-5 human lung cells. Biomolecules 2019; 9(11): 696.[http://dx.doi.org/10.3390/biom9110696] [PMID: 31690059]
[52]
Chen CN, Lin CPC, Huang KK, et al. Inhibition of SARS-CoV 3C-like protease activity by Theaflavin-3,30-digallate (TF3). Evid Based Complement Alternat Med 2005; 2(2): 209-15.[http://dx.doi.org/10.1093/ecam/neh081] [PMID: 15937562]
[53]
Park JY, Kim JH, Kim YM, et al. Tanshinones as selective and slow-binding inhibitors for SARS-CoV cysteine proteases. Bioorg Med Chem 2012; 20(19): 5928-35.[http://dx.doi.org/10.1016/j.bmc.2012.07.038] [PMID: 22884354]
[54]
Park JY, Yuk HJ, Ryu HW, et al. Evaluation of polyphenols from Broussonetia papyrifera as coronavirus protease inhibitors. J Enzyme Inhib Med Chem 2017; 32(1): 504-15.[http://dx.doi.org/10.1080/14756366.2016.1265519] [PMID: 28112000]
[55]
Yu MS, Lee J, Lee JM, et al. Identification of myricetin and scutellarein as novel chemical inhibitors of the SARS coronavirus helicase, nsP13 Bioorganic Med Chem Let 2012; 22: 4049-54.[http://dx.doi.org/10.1016/j.bmcl.2012.04.081]
[56]
Ryu YB, Jeong HJ, Kim JH, et al. Biflavonoids from Torreya nucifera displaying SARS-CoV 3CL(pro) inhibition. Bioorg Med Chem 2010; 18(22): 7940-7.[http://dx.doi.org/10.1016/j.bmc.2010.09.035] [PMID: 20934345]
[57]
Lin CW, Tsai FJ, Tsai CH, et al. Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and plant-derived phenolic compounds. Antiviral Res 2005; 68(1): 36-42.[http://dx.doi.org/10.1016/j.antiviral.2005.07.002] [PMID: 16115693]
[58]
Cheng PW, Ng LT, Chiang LC, Lin CC. Antiviral effects of saikosaponins on human coronavirus 229E in vitro. Clin Exp Pharmacol Physiol 2006; 33(7): 612-6.[http://dx.doi.org/10.1111/j.1440-1681.2006.04415.x] [PMID: 16789928]
[59]
Shen L, Niu J, Wang C, et al. High-throughput screening and identification of potent broadspectrum inhibitors of coronaviruses. J Virol 2019; 93(12): e00023-19.[http://dx.doi.org/10.1128/JVI.00023-19] [PMID: 30918074]
[60]
Müller C, Schulte FW, Lange-Grünweller K, et al. Broad-spectrum anti-viral activity of the eIF4A inhibitor silvestrol against corona-and picornaviruses Anti-viral Res 2018; 150: 123-9.
[61]
Wu CY, Jan JT, Ma SH, et al. Small molecules targeting severe acute respiratory syndrome human coronavirus. Proc Natl Acad Sci USA 2004; 101(27): 10012-7.[http://dx.doi.org/10.1073/pnas.0403596101] [PMID: 15226499]
[62]
Cao J, Forrest JC, Zhang X. A screen of the NIH Clinical Collection small molecule library identifies potential anti-coronavirus drugs. Antiviral Res 2015; 114: 1-10.[http://dx.doi.org/10.1016/j.antiviral.2014.11.010] [PMID: 25451075]
[63]
Chiow KH, Phoon MC, Putti T, Tan BK, Chow VT. Evaluation of antiviral activities of Houttuynia cordata Thunb. extract, quercetin, quercetrin and cinanserin on murine coronavirus and dengue virus infection. Asian Pac J Trop Med 2016; 9(1): 1-7.[http://dx.doi.org/10.1016/j.apjtm.2015.12.002] [PMID: 26851778]
[64]
Kim DW, Seo KH, Curtis-Long MJ, et al. Phenolic phytochemical displaying SARS-CoV papain-like protease inhibition from the seeds of Psoralea corylifolia. J Enzyme Inhib Med Chem 2014; 29(1): 59-63.[http://dx.doi.org/10.3109/14756366.2012.753591] [PMID: 23323951]
[65]
Tahir Khan M, Arif A, Qiankun W, Muhammad I, et al. Marine natural compounds as potents inhibitors against the main protease of SARSCoV-2. A molecular dynamic study. J Biomol Struct Dyn 2020.[http://dx.doi.org/10.1080/07391102.2020.1769733]
[66]
Wen CC, Shyur LF, Jan JT, et al. Traditional Chinese medicine herbal extracts of Cibotium barometz, Gentiana scabra, Dioscorea batatas, Cassia tora, and Taxillus chinensis inhibit SARS-CoV replication. J Tradit Complement Med 2011; 1(1): 41-50.[http://dx.doi.org/10.1016/S2225-4110(16)30055-4] [PMID: 24716104]
[67]
Li SY, Chen C, Zhang HQ, et al. Identification of natural compounds with antiviral activities against SARS-associated coronavirus. Antiviral Res 2005; 67(1): 18-23.[http://dx.doi.org/10.1016/j.antiviral.2005.02.007] [PMID: 15885816]
[68]
Hassan STS. Shedding Light on the Effect of Natural Anti-Herpesvirus Alkaloids on SARS-CoV-2: A Treatment Option for COVID-19. Viruses 2020; 12(4): 476.[http://dx.doi.org/10.3390/v12040476] [PMID: 32340120]
[69]
ul Qamar MT, Alqahtani SM, Alamri MA, Chen L-L. Structural basis of SARS-CoV-2 3CLpro and anti-COVID-19 drug discovery from medicinal plants J PharmaAnal 2020; 10(4): 313-19.
[70]
Chen F, Chan KH, Jiang Y, et al. In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds. J Clin Virol 2004; 31(1): 69-75.[http://dx.doi.org/10.1016/j.jcv.2004.03.003] [PMID: 15288617]
[71]
Kim JY, Kim YI, Park SJ, Kim IK, Choi YK, Kim SH. Safe, high-throughput screening of natural compounds of MERS-CoV entry inhibitors using a pseudovirus expressing MERS-CoV spike protein. Int J Antimicrob Agents 2018; 52(5): 730-2.[http://dx.doi.org/10.1016/j.ijantimicag.2018.05.003] [PMID: 29772395]
[72]
Skariyachan S, Gopal D, Muddebihalkar A, Uttarkar A, Niranjan V. Natural lead molecules probably act as potential inhibitors against prospective targets of SARS-CoV-2: Therapeutic insight for COVID-19 from computational modelling, molecular docking and dynamic simulation studies. Research Square [http://dx.doi.org/10.21203/rs.3.rs-33180/v1]
[73]
Zhang CH, Wang YF, Liu XJ, et al. Antiviral activity of cepharanthine against severe acute respiratory syndrome coronavirus in vitro. Chin Med J (Engl) 2005; 118(6): 493-6.[PMID: 15788131]


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VOLUME: 26
ISSUE: 41
Year: 2020
Published on: 03 September, 2020
Page: [5278 - 5285]
Pages: 8
DOI: 10.2174/1381612826666200903122536
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