Potential Medicinal Plants for the Treatment of Dengue Fever and Severe Acute Respiratory Syndrome-Coronavirus

biomolecules Review Potential Medicinal Plants for the Treatment of Dengue Fever and Severe Acute Respiratory Syndrome-Coronavirus Mohammed S. M. Saleh and Yusof Kamisah * Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Center, Cheras 56000, Kuala Lumpur, Malaysia; [email protected] * Correspondence: [email protected]; Tel.: +60-3-9145-9575; Fax: +60-3-9145-9547 Abstract: While dengue virus (DENV) infection imposes a serious challenge to the survival of humans worldwide, severe acute respiratory syndrome-coronavirus (SARS-CoV) remains the most devastating pandemic in human history. A significant number of studies have shown that plant- derived substances could serve as potential candidates for the development of safe and efficacious remedies for combating these diseases. Different scientific databases were used to source for literature on plants used against these infections. Thirty-five studies described the traditional use of 25 species from 20 families for treating DENV infection with Carica papaya and Euphorbia hirta were the most widely used across different regions. 13 in vivo studies, 32 in vitro studies, and eight clinical studies were conducted on 30 species from 25 families against different DENV serotypes, while plants from 13 families were reported to inhibit different forms of SARS-CoV, all of which were investigated through in vitro studies. Phytoconstituents belonging to various chemical classes were identified to show a wide range of antiviral activity against these infections. Extensive studies on the potentials of medicinal plants are needed to confirm their efficacy. This paper reveals the capabilities of medicinal plants and their phytochemicals in inhibiting DENV and SARS-CoV infections. Keywords: dengue virus; medicinal plants; ethnobotany; pharmacology; phytochemical; SARS-CoV Citation: Saleh, M.S.M.; Kamisah, Y. Potential Medicinal Plants for the Treatment of Dengue Fever and 1. Introduction Severe Acute Respiratory According to the World Health Organization (WHO), infectious diseases remain the Syndrome-Coronavirus. Biomolecules 2021, 11, 42. https://doi.org/ sixth leading cause of deaths globally [1]. Emerging and reemerging infectious diseases 10.3390/biom11010042 have continued to be a persistent threat to human population. Among numerous infectious diseases, viral diseases caused by varieties of old and new viruses have imposed a serious Received: 15 December 2020 challenge to the survival of mankind. Viral infections remain one of the main causes of Accepted: 27 December 2020 death worldwide [2]. It is terrifying that the number of patients diagnosed with these infec- Published: 30 December 2020 tions keeps on increasing every year. Among the top perilous viral diseases are Ebola (over 11,000 deaths in 2019) [3], acquired immunodeficiency syndrome (AIDS) which accounted Publisher’s Note: MDPI stays neu- the deaths of 1.1 million people globally [4], influenza (300,000–500,000 deaths yearly) [5,6], tral with regard to jurisdictional clai- dengue fever (over 390 million, of which 96 million manifest clinically) [7], and severe ms in published maps and institutio- acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (also known as COVID-19 in the nal affiliations. 2019 outbreak) (over 60 million cases with approximately 1,416,292 deaths worldwide) [1]. With the emergence of new viral strains and increasing resistance to standard antiviral therapy, and the fact that most of the available antiviral therapies are non-specific for particular viruses [8], the key focus of medical research is therefore centered on the devel- Copyright: © 2020 by the authors. Li- censee MDPI, Basel, Switzerland. opment of specific and cost-effective antiviral regimens [9,10], which include alternative This article is an open access article treatment from herbal sources. At present, several antiviral vaccinations are available distributed under the terms and con- including human papilloma virus [11], hepatitis A and B virus [12], varicella, measles, ditions of the Creative Commons At- mumps, rubella [13], and rabies [14]. However, there are still no vaccines for a few other tribution (CC BY) license (https:// viral infections. creativecommons.org/licenses/by/ Dengue fever is a viral infection that has imposed serious economic burdens in both 4.0/). tropical and sub-tropical regions [15]. More than 300 million cases are recorded annually Biomolecules 2021, 11, 42. https://doi.org/10.3390/biom11010042 https://www.mdpi.com/journal/biomolecules Biomolecules 2021, 11, x FOR PEER REVIEW 2 of 26 mumps, rubella [13], and rabies [14]. However, there are still no vaccines for a few other viral infections. Biomolecules 2021, 11, 42 Dengue fever is a viral infection that has imposed serious economic2 burdens of 25 in both tropical and sub-tropical regions [15]. More than 300 million cases are recorded annually with nearly 22,000 deaths [16]. Globally, dengue fever affects approximately 2.5 billion with nearly 22,000people deaths with [an16 ].estimated Globally, 50–100 dengue million fever new affects cases approximately annually [17]. 2.5The billion endemic disease people with anoccurs estimated in more 50–100 than million100 countries new casesincluding annually Africa, [ 17Asia,]. The America, endemic Eastern disease Mediterranean occurs in moreand than Western 100 countries Pacific including being the Africa,most affected Asia, America, regions [18] Eastern (Figure Mediterranean 1). Recently, the occur- and Western Pacificrence being of dengue the most has affected rapidly regionsincreased, [18 ]reaching (Figure1 the). Recently, pandemic the level occurrence [19]. More than 20 of dengue has rapidlyAfrican increased,countries were reaching affected the by pandemic an epidemic level between [19]. More 1960 than and 202017. African However, many countries were affectedoutbreaks by are an never epidemic officially between reported 1960 and[20]. 2017.Dengue However, fever is manycaused outbreaks by four distinct but are never officiallyantigenically reported related [20]. Dengue flavivirus fever serotypes is caused with by dengue four distinct virus (DENV) but antigenically type-2 (DENV-2) re- related flavivirusported serotypes to be more with deadly dengue than virus all (DENV)other sero type-2types [21]. (DENV-2) The disease reported is prevalent to be in urban more deadly thanand all semi-urban other serotypes areas [and21]. is The transmitted disease is by prevalent female Aedes in urban aegypti and mosquitoes semi-urban [22]. The in- areas and is transmittedcubation period by female afterAedes the virus aegypti getsmosquitoes into the human [22]. Thebody incubation varies from period 3–14 days, after after the virus getswhich into symptoms the human ranging body from varies mild from to severe 3–14 days, begin afterto manifest. which symptomsEarly symptoms may ranging from mildinclude to severeheadache, begin fever, to manifest.severe muscle, Early and symptoms joint pain may [23]. includeSevere cases headache, are characterized fever, severe muscle,by hemorrhagic and joint fever pain [syndrome,23]. Severe which cases may are characterizedresult in dengue by hemorrhagicshock syndrome [24]. Its fever syndrome,treatment which may includes result standard in dengue management shock syndrome of general [24]. fever Its treatment as well as includes other symptomatic standard managementtreatments of [25]. general Dengvaxia, feveras the well first as dengue other vaccine, symptomatic was licensed treatments a few [ 25years]. back for Dengvaxia, theclinical first dengue use [26]. vaccine, The safety was licensed of the vaccine a few years however, back foris still clinical questionable use [26]. due The to findings safety of the vaccinethat it however, could increase is still the questionable risk of dengue due fever to findings severity that in individuals it could increase with no the prior history risk of dengue feverof DENV severity infection in individuals [27]. with no prior history of DENV infection [27]. Europe North America Asia Africa South America Australia Figure 1. Global map showing the regions affected by dengue. Adapted from [28]. Figure 1. Global map showing the regions affected by dengue. Adapted from [28]. On the other hand,On the the other novel hand, COVID-19 the novel is currentlyCOVID-19 a is global currently health a global crisis health threatening crisis threatening the whole world.the whole It has world. swiftly It spreadhas swiftly across spread various across countries various countries from its from discovery its discovery in in Wu- Wuhan City, Hubeihan ProvinceCity, Hubei of ChinaProvince [29 of]. AsChina of 9 [29]. December As of 9 2020, December over 602020, million over cases60 million of cases of COVID-19 andCOVID-19 1,416,292 deathsand 1,416,292 have been deaths reported have been [1]. Therereported have [1]. been There two have incidents been two of incidents of transmission from animal β-coronaviruses to humans in the last two decades which had transmission from animal β-coronaviruses to humans in the last two decades which had resulted in serious diseases [30]: severe acute respiratory syndrome coronavirus (SARS- resulted in serious diseases [30]: severe acute respiratory syndrome coronavirus (SARS- CoV), which was passed from bats onto humans through palm civet cats (intermediary CoV), which was passed from bats onto humans through palm civet cats (intermediary host) host) in China in 2002–2003 [31], and Middle East respiratory syndrome coronavirus in China

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