Peruvian plants of traditional use as potential sources of molecules with activity against COVID-19

Peruvian plants of traditional use as potential sources of molecules with activity against COVID-19

Plantas peruanas de uso tradicional como fuente potencial de moléculas con actividad contra la COVID-19

About the authors:
  • 0000-0001-5769-8209 Delgado-Paredes, Guillermo E. 1 2 *
  • 0000-0002-3518-1847 Delgado-Rojas, Paulo R. 3
  • 0000-0003-3525-6711 Rojas-Idrogo, Consuelo 1 2
  • 1  Universidad Nacional Pedro Ruiz Gallo, Facultad de Ciencias Biológicas, Laboratorio de Cultivo de Tejidos Vegetales y Recursos Genéticos. Lambayeque, Perú.
  • 2  Vicerrectorado de Investigación (UNPRG), Laboratorio General de Biotecnología. Lambayeque, Perú.
  • 3  Universidad San Martín de Porres, Facultad de Medicina Humana, Filial Norte. Chiclayo. Perú.
Authors notes:
Corresponding author: guidelg2015@yahoo.es

The authors declare that there is no conflict of interest

Guillermo E. Delgado-Paredes: General design of the study. Interpretation and discussion of results.

Paulo R. Delgado-Rojas: Preparation of tables. Interpretation and discussion of results.

Consuelo Rojas-Idrogo: General design of the study. Interpretation and discussion of results.

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License

view the permissions of this license
RESUMEN
Introducción:

La situación actual de la COVID-19 es un gran problema para la población humana. En la actualidad, no hay medicamentos curativos disponibles en el mercado. Los investigadores están haciendo todo lo posible para producir fármacos con que luchar contra la enfermedad. Se están considerando varios esfuerzos basados en diferentes orientaciones del conocimiento científico y en las tecnologías para el tratamiento de la enfermedad. Desafortunadamente, ninguno de estos medicamentos funciona absolutamente contra la corriente pandémica. Por lo tanto, las moléculas bioactivas de plantas, animales y microorganismos podrían ser una mejor opción para tratar la COVID-19.

Objetivo:

Revisar la literatura sobre especies de la flora del Perú utilizadas en el tratamiento de enfermedades respiratorias y destacar las plantas con posible producción de metabolitos secundarios y lectinas vegetales potencialmente útiles como alternativa frente a la COVID-19.

Métodos:

Se revisaron artículos de literatura científica relacionados con el uso de la medicina tradicional en Perú, China e India para el tratamiento de enfermedades respiratorias, así como la información sobre lectinas vegetales y metabolitos secundarios con potencial utilidad contra la COVID-19.

Resultados:

Se presenta una amplia relación de géneros y especies de la flora del Perú con gran potencial contra la COVID-19. La mayoría de estas especies pertenecen a las familias Asteraceae, Loranthaceae, Piperaceae, Viscaceae y Zingiberaceae. Numerosas especies son endémicas del Perú.

Conclusiones:

La flora del Perú tiene más de 22 000 especies de plantas. Muchas de estas especies se utilizan tradicionalmente en el tratamiento de enfermedades respiratorias y pueden ser potencialmente útiles en el tratamiento de la COVID-19.

ABSTRACT
Introduction:

The current situation of COVID-19 is a big issue for the human population. At present, no healing drug is available in the market. Researchers are doing their best to produce drugs to fight the disease. Various efforts are being considered based on different directions of scientific knowledge and technologies for the treatment of the disease. Unfortunately, none of these drugs works absolutely against the pandemic. Therefore, bioactive molecules from plants, animals and microorganisms could be a better option to treat COVID-19.

Objective:

Review the literature about species of the flora of Peru used for the treatment of respiratory diseases and highlight the plants with potential in the production of secondary metabolites and plant lectins as an alternative against COVID-19.

Methods:

A review was conducted of scientific articles related to the use of traditional medicine in Peru, China, and India for the treatment of respiratory diseases, as well as information about plant lectins and secondary metabolites potentially useful against COVID-19.

Results:

A long list is presented of genera and species of the flora of Peru with great potential against COVID-19. Most of these species belong to the Asteraceae, Loranthaceae, Piperaceae, Viscaceae and Zingiberaceae families. Numerous species are endemic to Peru.

Conclusions:

The flora of Peru has more than 22 000 plant species. Many of these species are traditionally used in the treatment of respiratory diseases and are potentially useful for the treatment of COVID-19.

Keywords:
    • flora of Peru;
    • plant lectins;
    • respiratory diseases;
    • SARS-CoV-2;
    • secondary metabolites.
Palabras clave:
    • flora del Perú;
    • lectinas de plantas;
    • enfermedades respiratorias;
    • SARS-CoV-2;
    • metabolitos secundarios.

Introduction

Several epidemics and pandemics have afflicted humanity throughout its history causing the death of millions of people around the world. In the middle of the 14th century the Black Death or Pestilence caused by the bacterium Yersinia pestis killed 75-200 million people in Europe, Eurasia and North Africa, becoming the pandemic with the most deaths in human history1 In the 20th century, three pandemics: Spanish influenza (1918-1920), Asian influenza (1957) and Hong Kong influenza (1968) reported around 80 to 100 (according to recent estimates), two and four millions of death, respectively.2

The identification and characterization of a novel coronavirus associated with Severe Acute Respiratory Syndrome (SARS) have renewed interest in this Coronaviridae family.3 According to published reports, the SARS-Coronavirus 2 or SARS-CoV-2 (formerly named as 2019-nCoV) that causes the coronavirus disease 2019 (COVID-19) appeared for the first time in Wuhan (China) in December 2019 as a result of zoonotic transmission4 with probable bat origin.5 This disease shown a pneumonia outbreak has been declared a world pandemic by the World Health Organization,6 and until December 2020, more than 75.5 million infected and more than 1.67 million deaths have been reported worldwide.7

SARS-CoV-2, belongs Nidovirales order, of the Coronaviridae family. Its virion has a single (+) stranded RNA, with symmetric helical nucleocapsid8 that encodes several proteins including four main structural glycoproteins: spike (S); small envelope (E); membrane (M) and nucleocapsid phosphoprotein (N). Other proteins have non structural functions such as RNA dependent RNA polymerase (RdRp), coronavirus main protease (3CLpro), and papain-like protease (PLPro).9 These proteases are required for processing of the viral proteins.10) The hemagglutinin esterase (HE) is also a protein found in the SARS-CoV-2 envelope11,12 Patiens with COVID-19 pneumonia show a histopathological spectrum distinguished by variable patterns of epithelial damage, vascular complications, fibrosis and inflammation.13

Since the dawn of humanity, a variety of plant have been used as alternative methods to the treatments of diseases. Respiratory illness are specially treated with medicinal plants, thus they could be a good alternative to COVID-19 treatment. Particularly in a current context where there is not specific drug or vaccine against COVID-19. Recently studies has shown antiviral activity of medicinal plant extracts against virus such as Echovirus, a serotype of enteroviruses that infected millions of people,14 and Avian infectious bronchitis virus (IBV), a member of the coronavirus15 For this reason, potential applications of plant biotechnology against COVID-19, such as diagnostic reagents, vaccine candidates and antiviral drugs that inhibit the viral replication cycle, have been recently emphasized.16 The use of plant biomolecules, such as antibiotics and vaccines, is limited; however, an efficient combination of the synergistic antiviral effects against COVID-19 by plant-based molecules whit other potential drugs shows to be promising.17 These antiviral drugs include ritonavir and lopinavir, HIV protease inhibitors; ribavirin, faviparivir, and remdesivir, nucleoside analogs; galidesivir, adenosine analogue; and azvudine (reverse transcriptase inhibitor).18

Traditional Peruvian medicine has accumulated a wide range of knowledge on the use of plants for several millennia, for the treatment of various diseases. This knowledge has been transmitted only orally and there is no documentation about the traditional medicine practices used by pre-Columbian cultures such as Mochica, Chimu, Paracas, Nazca and others, or Inca civilization. Our main in this review is to show the international scientific community the potential of plant species of the flora of Peru in the treatment of respiratory diseases and in obtaining lectins and secondary metabolites, as well as the production of vaccines, against COVID-19.

Methods

It was reviewed the literature published regarding the use of traditional medicial plants for the treatment of respiratory diseases in Peru, China and India (Ayurvedic medicine). It was highlighted the information about the isolation of plant lectins and secondary metabolites, published between 2010 to 2020, with potential utility in the treatment of COVID-19, using the combination of words “plant lectins and plant secondary metabolites against Coronavirus or COVID-19”. The inclusion criteria were: manuscripts in all languages with English abstracts and full text online available, and plants used in traditional medicine in various countries in the treatment of respiratory diseases. In most cases the Scopus database was use. Book and scientific articles about the flora of Peru and the flora of North of Peru, published between 1993 to 2010, were also considered in the present work. Finally, a comparative study between these plant species with genera and species related to the flora of Peru, was showed.

Results

Use of Peruvian medicinal plants in the treatment of respiratory diseases

A first strategy is the use of Peruvian medicinal plants to treat respiratory diseases such as asthma, bronchitis, chest pain, chills, compulsive cough, cold with high mucus, colds, cough, flu, inflammation of the lungs, lungs, phlegm, pneumonia, pulmonary disease. In Peru, traditional and complementary alternative medicine is a practice developed by ancient pre-Columbian civilizations. This activity continues today and is mainly carried out by the rural population, sellers of medicinal plants in local markets (“remedieros”) and traditional healers (“curanderos”). However, there are no known studies on its application in the treatment against SARS-CoV-2.

According to a study published by Bussmann and Glenn (2010),19) a total of 91 plant species of Northern Peru belonging to 82 genera and 48 families were documented and identified as respiratory system herbal remedies. About 30% of these species correspond to three families, Asteraceae (15 species), Lamiaceae (8 species) and Fabaceae (5 species). However, not all reported species correspond to the native flora of northern Peru but rather are introduced species: Mangifera indica L. (mango), Medicago sativa L. (purple medic), Allium sativum L. (garlic), Zingiber officinale Rosc. (gingiber), among others. Although not all species have been tested on biological activity, the population uses them in the form of oral administration such as infusions of leaves, whole plants, stems, flowers, and other parts of the plant. This form of use is extremely important because no side effects or toxicity have been reported to date. In the same year, another study carried out by Vásquez et al. (2010)20 reported 130 species from Northern Peru of which 61 species (47%) are used in the treatment of respiratory diseases, highlighting the Asteraceae, Lamiaceae, and Fabaceae with 22, 6 and 6 species, respectively.20 A comparison between Bussmann and Glenn (2010)19 and Vásquez et al. (2010)20 studies, showed a high number of genera and species of the Asteraceae family used in the treatment of respiratory diseases. However, the isolation and identification of lectins and secondary metabolites in this family against COVID-19 were not reported.21,22,23).

Worldwide the traditional Chinese medicine (TCM) is widely applied in the treatment of various diseases. An example is a Chinese herbal mixture called Lianhuaqinqwen or Lian Hua Qing Wen, a mixture of 11 medicinal species, gypsum, and menthol, traditionally used to treat several respiratory diseases like cough, influenza, pneumonia, and bronchitis.24,25) Also, the Shu Feng Jie Du composition, composed of numerous plant species is used for the treatment of influenza and viral infections.22,26 Finally, a recent study showed that about 219 plants from 83 families exhibited antiviral activity of which 149 from 71 families were screened for the identification of secondary metabolites and their possible effect against COVID-19 pandemic.27

Use of medicinal plants due the presence of plant lectins and secondary metabolites

A second strategy was reviewed the literature related to the identification of lectins (Table 1) and secondary metabolites, used to the treatment of COVID-19, to compare them with the species and genera that occur in the flora of Peru (Table 2).

Plant lectins tested for their antiviral activity against SARS-CoV-2(21, 23, 35)

Potential use of Peruvian plant species in the treatment of COVID-19. Comparison with species reported in other parts of the world for the presence of plant lectins and secondary metabolites, tested for their antiviral activity against SARS-CoV-221,22,23,35

*Species of the flora of Peru.

Plant lectins

Plant lectins are a unique, natural, heterologous and ubiquitous group of proteins or carbohydrate-binding proteins with the ability to recognize and reversible bind to sugar structures present on the cell Surface.21,28,29 They are found in a wide range of organisms, from viruses to humans.30 In the pioneering study made by Keyaerts et al. (2007)21 thirty-three plants lectins isolated from 27 species of plants were tested for their antiviral activity against SARS-CoV and FIPV (Feline Infectious Peritonitis Virus). Among the total of plant lectins, the Mannose-specific agglutinins were highlighted. Other lectins are ML III, Nictaba and HHA, isolated from Viscum album L. “mistletoe” (Viscaceae), Nicotiana tabacum L. “tobacco” (Solanaceae) and Hippeastrum hybrid Hort. (Amaryllidaceae), respectively.21 The most potent lectins against the SARS-CoV were the plant lectin APA isolated from Allium porrum L., the plant lectin UDA isolated from Urtica dioica L., and the plant lectin Nictaba isolated from N. tabacum.21 Mistletoe lectins (ML I, ML II and ML III), isolated from V. album (European mistletoe), enhance immune responses to intranasally co-administered herpes simplex virus glycoprotein D2.31 In U. dioica, Urtica dioica agglutinin (UDA), was isolated showing efficacy on the replication of different SARS-CoV strains.32

In the flora of Peru, no species of the Viscum genus have been reported, however numerous species of the Dendrophthora and Phoradendron genera, belonging to the Viscaceae family, have been reported. These genera have 23 species each, as well 3 and 6 endemic species, respectively,33 and new studies allowed the incorporation of new species for both families, Loranthaceae, and Viscaceae, especially of the genus Phoradendron34 (Table 3).

Some families and genera of the flora of Peru with the greatest potential in plant lectins content for the treatment of COVID-1933,34

+ (No), addition of new species.34

[Number of genera (Endemic genera)].

Number of species, (Endemic species).

Genus (Number of species by genus).

Also, in the flora of Peru, 15 species of the genus Nicotiana, including N. tabacum, have been reported, of which 5 are endemic, as well as 538 species of Solanaceae with 162 endemic species. On the other hand, although H. hybrid has not been reported in the flora of Peru, there are 21 species of this genus as well as 135 species of Amaryllidaceae and 54 endemic species33 (Table 3). In the Urticaceae family, the flora of Peru registers the species U. dioica and 6 other species and one endemic, but no species of the Allium genus are reported33) (Table 2).

In a recent study, the antiviral activity of 4 lectins extracted and purified from the Northeastern Brazilian flora, from four Fabaceae species: Canavalia brasiliensis Mart. Ex. Benth. (ConBr), C. maritima Thouars. (ConM), Dioclea lasiocarpa Benth. (DLasiL) and D. scleroparpa Ducke (DSclerL) was reported. The lectins DSclerl y DLasilL showed potent antiviral activity against HIV-1 and respiratory sencitial virus (RSV), and ConBr and ConM against influenza A virus strain H3N2 and influenza B virus.35 In the flora of Peru, although only C. brasilienses have been reported, there are 12 species of the Canavalia genus with one endemic species and 12 species of the Dioclea genus (Table 2).33

Secondary metabolites

In the last decade (2010-2020) the scientific literature has been abundant in the discovery of numerous secondary metabolites with antiviral activity against SARS-CoV-2. This is the case of myricetin and scutellarein, which inhibited 90% of the ATPase activity of the SARS-CoV helicase (Nsp13), one of the non-structural proteins.36 Myricetin is a flavonoid with antioxidant properties, present in numerous plant species, and scutellarein is a flavone isolated in Scutellaria laterifolia L. (Lamiaceae) as well as in the fern Asplenium belangeri (Bory) Kunze (Aspleniaceae). In the flora of Peru, 15 species of Scutellaria have been reported and 5 species are endemic,33 as well as 65 species of Asplenium and 2 endemic species.37

Other objectives has been the discovery of natural products as ACE2 (Angiotensin-converting enzyme 2)-blockers, and targeting the TMPRSS2 (Transmembrane serine protease, serine 2), papain-like proteinase (PLpro) and chymotrypsin-like protease [3CL(pro)].22

In the case of ACE2-blockers, several species were identified such a Berberis integerrima Bunge (Berberidaceae), Crataegus microphylla K. Koch (Rosaceae), Onopordum acanthium L. (Asteraceae) and Quercus infectoria Olivier (Fagaceae),38 as well as Rheum officinale Baill. and Polygonum multiflorum Thunb., both Polygonaceae species that produce emodin, an anthraquinone that significantly blocked the S protein and ACE2 interaction,39 and inhibit the 3a ion channel of SARS-CoV and HCoV-OC43.40 Of these species in the flora of Peru, only the genera Berberis with 32 species and 18 endemic, Crateagus with 1 species and Polygonum wih 11 species and 1 endemic have been recorded.33

Referent to targeting the TMPRSS2, several secondary plant metabolites have been identified. Thus, the flavonoides kaempherol, luteolin and quercetin, the most common flavonoids found in plants, such as olives, grapes, cauliflower, and others,41 significantly suppressed TMPRSS2 expression.42 Addittionally, sulforaphane [1-isothiocyanato-4-(methylsulfinyl)-butane], isolate from broccoli (Brassica oleraceae L.),43 downregulate the TMPRSS2 expression,44 and cryptotanshinone, the main active component in the root of Salvia miltiorrhiza Bunge (Lamiaceae)45,46 also shows anti-TMPRSS2 activity.47 In the flora of Peru B. oleraceae is not a native species although there are 4 reported native species of this genus, and although S. miltiorrhiza is not recorded there are 76 species of the genus Salvia with 35 endemic species.33

In the case of targeting papain-like proteinase (PLpro) six cinnamic amides were isolated from fruits from Tribulus terrestris L. (Zygophyllaceae), and among these terrestrimine showed the best inhibitory activity of SARS-CoV PLpro.48 Seven bioactive transhinones were isolated from S. miltiorrhiza, and the results showed that cryptotanshinone, tanshinone I and rosmariquinone were the most potent inhibitors of SARS-CoV PLpro.49 Likewise, nine diarylheptanoids were isolated from Alnus japonica (Thunb.) Steud. (Betulaceae), and among these hirsutenone showed the most significant inhibitory effect against SARS-CoV PLpro.50) In the flora of Peru, the Zygophyllaceae family registers 6 genera with 12 species and the Tribulus genus with 3 species: T. cistoides, T. longipetatalus and T. terrestris (Table 3). The Betulaceae family with a single genus (Alnus) and a single species, A. acuminata Kunth, and as already indicated, the Salvia genus registers 76 species with 36 endemic species.33

Referent, to targeting chymotrypsin-like protease [3CL(pro)] alkylated chalcones, specifically xanthoangelol E, isolated from Angelica keiskei (Miq.) Koidz., showed to be the most potent SARS-Co-V- 3CL(pro) inhibitor.51 Likewise, several tanshinones isolated from S. miltiorrhiza, specifically dihydrotanshinone I, showed the most potent SARS-Co-V- 3CL(pro) inhibitory effect52 Both plant species have also shown significant inhibitory effect against SARS-CoV PLpro.

Additionally, the effect of numerous flavonoids towards SARS-CoV-3CL(pro) was evaluated, observing that pectolinarin (isolated from Cirsium chanroenicum Nakai (Nakai), Asteraceae) showed the higher inhibitory effect.53 Only the Cirsium vulgare (Savi) Ten. species has been reported in the flora of Peru.33

In traditional Indian medicine (Ayurvedic and Siddha medicinal system) as well as in traditional Chinese medicine, numerous plant species used in the treatment of various diseases of the respiratory tract and of potential use against SARS-CoV-2 are reported.54 Among these species the following are mentioned: Piper nigrum L. and P. betle L. (Piperaceae), Cinchona officinalis L. (Rubiaceae), Zingiber officinale (Zingiberaceae), and others. Most of these species are not found in the flora of Peru. However, in the genus Piper 429 species have been registered with 302 endemic species, in the genus Cinchona, native to America, 18 species and 3 endemic species (C. delessertiana, C. glandulifera and C. nitida) and although Z. officinalis is not a native species, in the flora of Peru it is they have registered 6 genera of this family, 44 species and 7 endemic species (Table 4).33 In addition, in recent years new species of Peperomia (7), Piper (12) and Cinchona (8) have been added to the flora of Peru, highlighting the Rubiaceae family with a significant increase of 212 new species (Table 3).34) In the genus Piper, hundreds of secondary compounds have been isolated and identified showing different beneficial biological activities and medicinal properties.55,56 In C. officinalis, chloroquine, a synthetic form of quinine, isolated from cinchona bark, has been tested for its antiviral properties against SARS-CoV-1,21 and the Z. officinalis showed several chemical constituents, especially volatile oils, with antimicrobial activities for various bacteria, virus and fungus.57

Some families and genera of the flora of Peru with the greatest potential in plant secondary metabolites content for the treatment of COVID-1933,34

+ (No), addition of new species.34

[Number of genera (Endemic genera)].

Number of species, (Endemic species).

Genus (Number of species by genus).

*Endemic genus.

In the study by Bhuiyan et al. (2020)27 a wide list of species and genera that have potentially efficient secondary metabolites against SARS-CoV-2 is reported. About 68% of these species and genera are found in the flora of Perú,33 specifically the genera Baccharis, Capparis, Maytenus, Cyperus, Euphorbia, Acacia (Vachellia), Geranium, Strychnos, Ficus, Phyllanthus, Prunus and Viola, with more than 16 species/genus, as well as numerous endemic species. A special reference is for the Baccharis genus, widely distributed in the Neotropics with around 400 to 500 species, highlighting B. latifolia used in traditional medicine in Latin America for its anti-inflammatory properties.58 Other Baccharis species such as B. latifolia, B. genistelloides, and B. vacciniifolia are widely used in traditional Peruvian medicine as anti-inflammatory and in the treatment of respiratory diseases.20 As already indicated in the flora of Peru, 70 species of Baccharis have been registered with 20 endemic species.

In recent years, among the numerous secondary metabolites identified with activity against SAR-CoV-2, which have received more attention are: glycyrrhizin, baicalin, scutellarin, hesperetin, nicotinamide and quercetin that could have antiviral effect for their capacity for binding ACE2.59) The flavonoid glycyrrhizin is the major component in roots from licorice (Glycyrrhiza glabra L. and G. uralensis Fischer, Fabaceae), used in the traditional Chinese medicine for the treatment of bronchitis, with anti-oxidant and anti-inflammatory properties, and have been proven to inhibit infection of human respiratory syncitial virus (HRSV).60 Baicalin is a flavone glucoronide isolated from Scutellaria baicalensis Georgi (Lamiaceae), used in the Chinese medicine for its therapeutic effects, having exhibited antiviral activities for SARS coronavirus, and with potential to inhibit ACE in in vitro conditions.61 Recently it was reported that the extract of this species inhibited 3CLPro activity of the SARS-CoV virus-2 in vitro.62 Scutellarin is a glycosyloxyflavone isolated from Erigeron breviscapus (Vaniot) Hand. (Asteraceae) with broad pharmacological effects and widely used in Chinese medicine63) observing that it reduces the expression and activity of ACE in brain tissue in vivo and consequently could inhibit ACE2.64) Hesperetin, and to a lesser extent aloe emodin, are two phenolic compounds isolated from Isatis tinctoria var. indigotica L. (Brassicaceae) that inhibit cleavage activity of the 3CLPro of SARS-CoV-2.65 Hesperetin is a bioflavonoid abundant in Citrus aurantium L. and Citri Reticulate Pericarpium (Rutaceae, CRP), commonly called as Chenpi and widely used in traditional Chinese medicine.59 Quercetin is a flavonoid widely distributed in several species of Allium (Amaryllidaceae) such as onion (A. cepa L.), garlic (A. sativum) and leek (A. porrum) and in the latter species a significant potential in inhibition of ACE2 enzymes, has been observed, therefore of potential use against SARS-CoV-2.66 Other secondary metabolites such as betulinic acid, triterpenoid isolated from Betula pubescens Ehrh. (Betulaceae), showed the highest inhibitory effect on enzymatic activity of 3CLPro of SARS-CoV-2,67 and homoharringtonine, an alkaloid derived from Cephalotoxus fortuei Hook. (Cephalotaxaceae) showed potent antiviral activities against certain viruses such as rhabdovirus and coronavirus.68)

Conclusions

The flora of Peru is one of the richest and most varied in the world and with a high degree of endemism. Numerous species are used by traditional Peruvian medicine in the treatment of respiratory diseases. Species of the genera Baccharis (Asteraceae), Cinchona and Isertia (Rubiaceae) and Dendrophthora and Phoradendron (Viscaceae), are some that can be used against COVID-19, due to the potential presence of plant lectins and secondary metabolites.

Acknowledgment

  • The authors are grateful to Guillermo Uceda-Campos, Instituto de Química, Universidade de São Paulo, Brasil, for English improvement.

Referencias bibliográficas
  • 1. Valtueña AA, Mittnik A, Key FM, Haak W, Allmäe R, Belinskij A, et al. The stone age plague and its persistence in Eurasia. Curr Biol. 2017;27:3683-91.e8. Doi: https://doi.org/10.1016/j.cub.2017.10.025
  • 2. AtlasMagazine. 20th and 21st century’s major pandemics. Atlas-mag.net 2020[acceso: 03/12/2020]. Disponible en: Disponible en: https://www.atlas-mag.net/en/article/20th-and-21st-century-s-major-pandemics
  • 3. Rota PA, Oberste MS, Monroe SS, Nix WA, Campagnoli R, Icenogle JP, et al. Characterization of a novel coronavirus associated with severe acute respiratory síndrome. Science. 2003;300:1394-9. Doi: https://doi.org/10.1126/science.1085952
  • 4. Mackenzie JS, Smith DW. COVID-19: a novel zoonotic disease caused by a coronavirus from China: what we know and what we don’t. Microbiol Aust. 2020;41:45-50. Doi: https://doi.org/10.1071/MA20013
  • 5. Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579:270-3. Doi: https://doi.org/10.1038/s41586-020-2951-z
  • 6. WHO (World Health Organization). WHO announces COVID-19 outbreak a pandemic. March 2020 [acceso: 27/12/2020]. Disponible en: Disponible en: https://www.euro.who.int/en/health-topics/health-emergencies/coronavirus-covid-19/news/news/2020/3/who-announces-covid-19-outbreak-a-pandemic
  • 7. JHU CSSE (Johns Hopkins University Center for Systems Science and Engineering, SandData/COVID-19) [acceso: 19/12/2020]. Disponible en: Disponible en: https://coronavirus.jhu.edu/map.html
  • 8. Khan S, Siddique R, Shereen MA, Ali A, Liu J, Bai Q, et al. Emergence of a novel coronavirus, severe acute respiratory sindrome coronavirus 2: biology and therapeutic options. J Clin Microbiol. 2020;58:e00187-e00120. Doi: https://doi.org/10.1128/JCM.00187-20
  • 9. Chen Y, Pan Y, Zhao ZJ. Structure analysis of the receptor binding of 2019-nCoV. Biochem Biophy Res Commun. 2020;525:135-40. https://doi.org/10.1016/j.bbrc.2020.02.071
  • 10. Báez-Santos YM, St John SE, Mesecar AD. The SARS-coronavirus papain-likenprotease: Structure, function and inhibition by designed antiviral compounds. Antivir Res. 2015;115:21-38. Doi: https://doi.org/10.1016/j.antiviral.2014.12.015
  • 11. Wang C, Zheng X, Gai W, Zhao Y, Wang H, Wang H. MERS-CoV virus-like particles produced in insect cells induce specific humoral and cellular immunity in rhesus macaques. Oncotarget. 2017;8:12686-694. Doi: https://doi.org/10.18632/oncotarget.8475
  • 12. Walls AC, Park YJ, Tortorice MA, Wall A, McGuire AT, Veesler D. Structure, function and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell. 2020;180:281-92. Doi: https://doi.org/10.1016/j.cell.2020.02.058
  • 13. von der Thüsen J, van der Eerden M. Histopathology and genetic susceptibility in COVID-19 pneumonia. Eur J Clin Invest. 2020;50:e13259. Doi: https://doi.org/10.1111/eci.13259
  • 14 . Ogbole OO, Toluwanimi EA, Según PA, Faleye TC, Adeniji AJ. In vitro antiviral activity of twenty-seven medicinal plant extracts from Southwest Nigeria against three serotypes of echoviruses. Virol J. 2018;15:110. Doi: https://doi.org/10.1186/s12985-018-1022-7
  • 15. Lelešius R, Karpovaitė A, Mickienė R, Drevinskas T, Tiso N, Ragažinskienė O, et al. In vitro antiviral activity of fifteen plant extracts against avian infectious bronchitis virus. BMC Vet Res. 2019;15:178. Doi: https://doi.org/10.1186/s12917-019-1925-6
  • 16. Capell T, Twyman RM, Armario-Najera V, Ma JK-C, Schillberg S, Christou P. Potential applications of plant biotechnology against SARS-CoV-2. Trends in Plant Science 2020;25(7). Doi: https://doi.org/10.1016/j.tplants.2020.04.009
  • 17. Prasad A, Muthamilarasan M, Prasad M. Synergistic antiviral effects against SARS-CoV-2 by plant-based molecules. Plant Cell Rep. 2020;39:1109-14. Doi: https://doi.org/10.1007/s00299-020-02560-w
  • 18. Li G, De Clercq E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov. 2020;19:149-50. Doi: https://doi.org/10.1038/d41573-020-00016-0
  • 19. Bussmann RW, Glenn A. Medicinal plants used in Peru for the treatment of respiratory disorders. Rev Peru Biol. 2010;17:331-46.
  • 20. Vásquez L, Escurra J, Aguirre R, Vásquez G, Vásquez LP. Plantas medicinales del norte del Perú. Fondo de Innovación, Ciencia y Tecnología (FINCyT) y Universidad Nacional Pedro Ruiz Gallo, Lambayeque (Perú). 2010. p. 382 .
  • 21. Keyaerts E, Li S, Vijgen L, Pannecouque C, Van Damme E, Peumans W, et al. Plant lectins are potent inhibitors of coronavirus by interfering with two targets in the viral replication cycle. Antivir Res. 2007;75:179-87. Doi: https://doi.org/10.1016/j.antiviral.2007.03.003
  • 22. Benarba B, Pandiella A. Medicinal plants as sources of active molecules against Covid-19. Front Pharmacol. 2020;11:1189. Doi: https://doi.org/10.3389/fphar.2020.01189
  • 23. Yonesi M, Rezazadeh A. Plants as a prospective source of natural anti-viral compounds and oral vaccines against COVID-19 coronavirus. Preprint - April 2020. Doi: https://doi.org/10.20944/preprints202004.0321.v1
  • 24. Ding Y, Zeng L, Li R, Chen Q, Zhou B, Chen Q, et al. The Chinese prescription lianhuaqingwen capsule exerts anti-influenza activity through the inhibition of viral propagation and impacts immune frunction. BMC Complement Altern Med. 2017;17:130. Doi: https://doi.org/10.1186/s12906-017-1585-7
  • 25. Runfeng L, Yunlong H, Jicheng H, Weiqy P, Qinhai M, Yongxia S, et al. Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2). Pharmacol Res. 2020;156:e104761. https://doi.org/10.1016/j.phrs.2020.104761
  • 26. Yang Y, Islam MS, Wang J, Li Y, Chen X. Traditional Chinese medicine in the treatment of patients infected with 2019-new coronavirus (SARS-CoV-2): A review and perspective. International J Biol Sci. 2020;16:1707-08. Doi: https://doi.org/10.7150/ijbs.45538
  • 27. Bhuiyan FR, Howlader S, Raihan T, Hasan M. Plants metabolites: Possibility of natural therapeutics against the COVID-19 pandemic. Front Med. 2020;7:e444. Doi: https://doi.org/10.3389/fmed.2020.00444
  • 28. Santos AFS, da Silva MDC, Napoleão TH, Paiva PMG, Correia MTS, Coelho LCBB. Lectins: function, structure, biological properties and potential applications. Curr Top Pept Protein Res. 2014 [acceso: 27/12/2020];15:41-62. Disponible en: Disponible en: http://hd1.handle.net/1822/43440 Disponible en: http://hd1.handle.net/1822/43440https://www.researchgate.net/publication/277708908_Lectins_Function_structure_biological_properties_and_potential_applications
  • 29. Mazalovska M, Kouakam JC. Lectins as promising therapeutics for the prevention and treatments of HIV and other potential coinfections. Hindawi BioMed Res Int. 2018; 2018:e3750646. Doi: https://doi.org/10.1155/2018/3750646
  • 30. Mitchell CA, Ramessar K, O’Keefe BR. Antiviral lectins: selective inhibitors of viral entry. Antivir Res . 2017;142:37-54. Doi: https://doi.org/10.1016/j.antiviral.2017.03.007
  • 31. Lavelle EC, Grant G, Pusztai A, Pfüller U, Leavy O, McNeela E, et al. Mistletoe lectins enhance immune responses to intranasally co-administered herpes simplex virus glycoprotein D2. Immunology. 2002;107:268-74. Doi: https://doi.org/10.1046/j.1365-2567.2002.01492.x
  • 32. Kumaki Y, Wandersee MK, Smith AJ, Zhou Y, Simmons G, Nelson NM, et al. Inhibitions of severe acute respiratory sindrome coronavirus replication in a lethal SARS-CoV BALB/c mouse model by stinging nettle lectin, Urtica dioica agglutinin. Antivir Res. 2011;90:22-32. Doi: https://doi.org/10.1016/j.antiviral.2011.02.003
  • 33. Brako L, Zarucchi J. Catálogo de las Angiospermas y Gimnospermas del Perú. Monogr. Syst Bot Missouri Bot. 1993;45.
  • 34. Ulloa C, Zarucchi JL, León B. Diez años de Adiciones a la Flora del Perú: 1993-2003. Arnaldoa (Edic. Esp.). 2004:1-242.
  • 35. Gondim ACS, da Silva SR, Mathys L, Noppen S, Liekens S, Sampaio AH, et al. Potent antiviral activity of carbohydrate-specific algal and leguminous lectins from the Brazilian biodiversity. Med Chem Commun. 2019;10:390. Doi: https://doi.org/10.1039/c8md00508g
  • 36. Yu MS, Lee J, Lee J, Kim Y, Chin YW, Jee JG, et al. Identification of myricetin and scutellarein as novel chemical inhibitors of the SARS coronavirus helicase, nsP13. Bioorg Med Chem Lett. 2012;22:4049-54. Doi: https://doi.org/10.1016/j.bmcl.2012.04.081
  • 37. León B. Aspleniaceae del Perú. Rev Peru Biol . Número especial 13:896s. En: León B, Roque J, Ulloa, Pitman N, Jørgensen PM, Cano A (eds). El libro rojo de las plantas endémicas del Perú. Facultad de Ciencias Biológicas, UNMSM, Lima, Perú. 2006. p. 45. [acceso: 27/12/2020]. Disponible en: Disponible en: https://sisbib.unmsm.edu.pe/BVRevistas/biologia/v13n2/pdf/a151.pdf
  • 38. Sharifi N, Souri E, Ziai SA, Amin G, Amanlou M. Discovery of new angiotensin converting enzyme (ACE) inhibitors from medicinal plants to treat hypertension using an in vitro assay. Daru. 2013;21:74. Doi: https://doi.org/10.1186/2008-2231-21-74
  • 39. Ho TY, Wu SL, Chen JC, Li CC, Hsiang CY. Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction. Antivir Res. 2007;74:92-101. https://doi.org/10.1016/j.antiviral.2006.04.014
  • 40. Schwarz S, Wang K, Yu WJ, Sun B, Schwarz W. Emodin inhibits current through SARS-associated coronavirus 3a protein. Antiviral Res. 2011;90:64-69. Doi: https://doi.org/10.1016/j.antiviral.2011.02.008
  • 41. Kozłowska A, Szostak-Wegierek D. Flavonoids - food sources and health benefits. Roczniki Państwowego Zakładu Higieny. 2014;68:79-85.
  • 42. Mamouni K, Zhang S, Li X, Chen Y, Yang Y, Kim J, et al. A novel flavonoid composition targets androgen receptor signaling and inhibits prostate cáncer growth in periclinal models. Neoplasia. 2018;20:789-99. Doi: https://doi.org/10.1016/j.neo.2018.06.003
  • 43. Naser S, Amiri-Beshelib B, Sharifi-Mehra S. The isolation and determination of sulforaphane from broccoli tissues by reverse phase-high performance liquid chromatography. J Chin Chem Soc. 2011;58:906-10. Doi: https://doi.org/10.1002/jccs.201190143
  • 44. Meyer M, Jaspers I. Respiratory protease/antiprotease balance determines susceptibility to viral infection and can be modified by nutritional antioxidants. Am. J. Physiol. Lung Cell Mol Physiol. 2015;308:1189-201. Doi: https://doi.org/10.1152/ajplung.00028.2015
  • 45. Zeng J, Fan Y-J, Tan B, Su H-Z, Li Y, Zhang L-L, et al. Charactering the metabolism of cryptotanshinone by human P450 enzymes and uridine diphosphate glucoronosyltransferases in vitro. Acta Pharmacol Sin. 2018;39:1393-404. Doi: https://doi.org/10.1038/aps.2017.144
  • 46. Wu Y-H, Wu Y-R, Li B, Yan Z-Y. Crytotanshinone: A review of its pharmacology activities and molecular mechanisms. Fitoterapia. 2020;145:104633. Doi: https://doi.org/10.1016/j.fitote.2020.104633
  • 47. Xu D, Lin TH, Li S, Da J, Wen XQ, Ding J, et al. Cryptotanshinone suppresses androgen receptor-mediated growth in androgen dependent and castration resistant prostate cancer cells. Cancer Lett. 2012;316:11-22. Doi: https://doi.org/10.1016/jcanlet.2011.10.006
  • 48. Song YH, Kim DW, Curtis-Long MJ, Yuk HJ, Wang Y, Zhuang N, et al. Papain-like protease (PLpro) inhibitory effects of cinnamic amides from Tribulus terrestris fruits. Biol Pharm Bull. 2014;37:1021-8. Doi: https://doi.org/10.1248/bpb.b14-00026
  • 49. Park JY, Kim JH, Kim YM, Jeong HJ, Kim DW, Park KH, et al. Tanshinones as selected and slow-binding inhibitors for SARS-CoV cysteine proteases. Bioorg Med Chem. 2012a;20:5928-35. Doi: https://doi.org/10.1016/j.bmc.2012.07.038
  • 50. Park J-Y, Jeong HJ, Kim JH, Kim YM, Park S-J, Kim D, et al. Diarylheptanoids from Alnus japonica inhibitor papain-like protease of severe acute respiratory sindrome coronovairus. Bioorg Med Chem. 2012b;5:2036-42. Doi: https://doi.org/10.1248/bpb.b12-00623
  • 51. Park JY, Ko JA, Kim DW, Kim YM, Kwon H-J, Jeong HJ, et al. Chalcones isolated from Angelica keiskei inhibit cysteine proteases of SARSCoV. J Enzyme Inhib Med Chem. 2016;31:23-30. Doi: https://doi.org/10.3109/14756366.2014.1003215
  • 52. Park OK, Choi JH, Park JH, Kim IH, Yan BC, Ahn JH, et al. Comparison of neuroprotective effects of five major lipophilic diterpenoids from Danshen extract against experimentally induced transient cerebral ischemic damage. Fitoterapia. 2012;83:1666-74. Doi: https://doi.org/10.1016/j.fitote.2012.09.020
  • 53. Jo S, Kim S, Shin DH, Kim MS. Inhibition of SARS-CoV 3CL protease by flavonoids. J Enzyme Inhib Med. Chem. 2020;35:145-51. Doi: https://doi.org/10.1080/14756366.2019.1690480
  • 54. Srivastava AK, Chaurasia JP, Khan R, Dhand C, Verma S. Role of medicinal plants of traditional use in recuperating devasting COVID-19 situation. Medicinal Aromat Plants. 2020;9:359. Doi: https://doi.org/10.35248/2167-0412.20.9.359
  • 55. Parmar VS, Jain SC, Bisht KS, Jain R, Taneja P, Jha A, et al. Phytochemistry of the genus Piper. Phytochemistry. 1997;46:597-673. https://doi.org/10.1016/S0031-9422(97)00328-2
  • 56. Salehi B, Zakaria ZA, Gyawali R, Ibrahim SA, Rajkovic J, Shinwari ZK, et al. Piper species: A comprehensive review on their phytochemistry, biological activities and applications. Molecules. 2019;24:1364. Doi: https://doi.org/10.3390/molecules24071364
  • 57. Mao QQ, Xu XY, Cao SY. Bioactive compounds and bioactivities of ginger (Zingiber officinale Roscoe). Foods. 2019;8:185. Doi: https://doi.org/10.3390/foods8060185
  • 58. Prada J, Orduz-Díaz L, Coy-Barrera E. Baccharis latifolia: A lowly-valued asteraceous plant with chemical and medicinal potential in neotropics. Revista de la Facultad de Ciencias Básicas (Universidad Militar Nueva Granada). 2016;12:92-105. Doi: http://dx.doi.org/10.18359/rfcb.1858
  • 59. Chen H, Du Q. Potential natural compounds for preventing 2019-n-CoV infection. Preprints, 2020. Doi: https://doi.org/10.20944/preprints202001.0358.v3
  • 60. Yeh CF, Wang KC, Chiang LC, Shieh DE, Yen MH, San Chang J. Water extract of licorice had anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines. J Ethnopharmacol. 2013;148:466-473. Doi: https://doi.org/10.1016/j.jep.2013.04.040
  • 61. Deng YF, Aluko RE, Jin Q, Zhang Y, Yuan LJ. Inhibitory activities of baicalin against renin and angiotensin-converting enzyme. Pharm Biol. 2012;50:401-06. Doi: https://doi.org/10.3109/13880209.2011.608076
  • 62. Liu FY, Sun Q, Liang H, Li C, Lu R, Huang B, et al. Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro. bioRxiv. 2020:e35824. Doi: https://doi.org/10.1101/2020.04.10.035824
  • 63. Wang L, Ma Q. Clinical benefits and pharmacology of scutellarin: A comprehensive review. Pharmacol Ther. 2018;190:105-27. Doi: https://doi.org/10.1016/j.pharmthera.2018.05.006
  • 64. Wang W, Ma X, Han J, Zhou M, Ren H, Pan Q, et al. Neuroprotective Effect of Scutellarin on Ischemic Cerebral Injury by Down-Regulating the Expression of Angiotensin-Converting Enzyme and AT1 Receptor. PLoS One. 2016;11(1):e0146197. Doi: https://doi.org/10.1371/journal.pone.0146197
  • 65. Lin C-W, Tsai F-J, Tsai CH, Lai C-C, Wan L, Ho T-Y, et al. Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and plant-derived phenolic compounds. Antiviral Res. 2005;68:36-42. Doi: https://doi.org/10.1016/j.antiviral.2005.07.002
  • 66. Thuy BTP, My TTA, Hai NTT, Hieu LT, Hoa TT, Loan HTP, et al. Investigations into SARS-Co-2 resistance of compounds in garlic essential oil. ACS Omega. 2020;5:8312-20. Doi: https://doi.org/10.1021/acsomega.0c00772
  • 67. Wen CC, Kuo YH, Jan JT, Liang PH, Wang SY, Liu HG, et al. Specific plant terpenoids and lignoids possess potent antiviral activities against severe acute respiratory syndrome coronavirus. J Med Chem. 2007;50:87-4095. Doi: https://doi.org/10.1021/jm070295s
  • 68. Choy K, Wong AY, Kaewpreedee P, Sia SF, Chen D, Hui KPY, et al. Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro. Antiviral Res. 2020;178:e104786. Doi: https://doi.org/10.1016/j.antiviral.2020.104786
History:
  • » Received: 21/01/2021
  • » Accepted: 09/03/2021
  • » Publicado : 01/12/2021

Enlaces refback

  • No hay ningún enlace refback.


Bookmark and Share


Copyright (c) 2022 Guillermo Eduardo Delgado Paredes, Paolo Delgado Rojas, Consuelo Rojas Idrogo

Licencia de Creative Commons
Esta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial 4.0 Internacional.