key: cord-0061168-ksxo5ytp
authors: Fongnzossie Fedoung, Evariste; Biwole, Achille Bernard; Nyangono Biyegue, Christine Fernande; Ngansop Tounkam, Marlene; Akono Ntonga, Patrick; Nguiamba, Véronique Priscille; Essono, Damien Marie; Forbi Funwi, Preasious; Tonga, Calvin; Nguenang, Guy Merlin; Kemeuze, Victor; Sonwa, Denis Jean; Tsabang, Nole; Bouelet, Isabelle Sandrine; Tize, Zra; Boum, Alexandre Teplaira; Momo Solefack, Marie Caroline; Betti, Jean Lagarde; Nouga Bissoue, Achille; Lehman, Leopold Gustave; Mapongmetsem, Pierre Marie; Nneme Nneme, Leandre; Ngono Ngane, Rosalie Annie; Ngogang Yonkeu, Jeanne
title: A review of Cameroonian medicinal plants with potentials for the management of the COVID-19 pandemic
date: 2021-03-26
journal: ADV TRADIT MED (ADTM)
DOI: 10.1007/s13596-021-00567-6
sha: c2c98bf4ffe2838099117a9d962617e31913db9c
doc_id: 61168
cord_uid: ksxo5ytp

Since the outbreak in December 2019, in Wuhan (China) of COVID-19, approved drugs are still lacking and the world is seeking effective treatment. The purpose of this article is to review the medicinal plants with potential to be used as complementary therapies against COVID-19. Bibliographic information was searched in several databases (Google Scholar, PubMed, Scopus, ScienceDirect, PROTA, ResearchGate and GLOBEinMED), to retrieve relevant papers on (1) plants used to manage common symptoms of COVID-19, (2) plant secondary metabolites with confirmed inhibitory effects on COVID-19 and (3) plants exhibiting pharmacological activities of relevance for COVID-19 management. A total of 230 species was recorded as potential source of ingredients for the fight against the 2019 novel corona virus. Of these species, 30 contain confirmed antiCOVID-19 secondary metabolites, 90 are used traditionally to manage at least 3 common symptoms of COVID-19, 10 have immunostimulant activity, 52 have anti-inflamatory activity, 14 have antiviral properties and 78 species are documented as used to treat malaria. A PCA analysis showing cluster formatting among the recorded species indicates 4 groups of species and an array of possibility of using individual species or a combination of species for their complementary effects. The authors argue that Cameroonian medicinal plants can be of potential contribution to the fight against COVID-19. Further applied research is needed to provide more scientific evidence for their efficacy, to establish standard formulations and clinical studies as part of efforts to develop therapies for COVID-19.

Corona viruses are well known in veterinary medicine. First discovered in the 1960s as parasites of infectious chicken bronchitis, they were later found to be responsible for serious epidemics in humans such as Severe Acute Respiratory Syndrome (SARS) in 2002/2003 and the Middle East Respiratory Syndrome (MERS) in 2012. Huang et al. (2020) reported in late December 2019, an outbreak of a mysterious pneumonia of unknown cause in the Huanan Seafood Wholesale Market, in Wuhan, Hubei, China. The causal agent of this disease was isolated and identified by Chinese scientists as a new strain of Corona virus, the SARS-CoV-2 or 2019 novel corona virus (2019-nCov) . Data obtained on patients with laboratory-confirmed 2019-nCoV infection in the hospital of Wuhan indicated that the common early symptoms of this disease were fever (98% of patients), cough (76%), and myalgia or fatigue (44%). Complications associated with this disease as observed in hospitalized patients included acute respiratory distress syndrome (29%), RNAaemia (15%), acute cardiac injury (12%) and secondary infections (10%).

Because this 2019-nCov is spread by human-to-human transmission via droplets or direct contact (Lai et al. 2020) , its emergence in China has caused a large global outbreak. According to the European Centre for Disease Prevention and Control, the worldwide situation update shows that since 31 December 2019 and as of 13 January 2021, a total of 84 532 824cases of COVID-19 have been reported worldwide, including 1,845,597 deaths (ECDC 2020) . During the same period, the African continent has reported 2,832,753 cases (26,846 cases reported for Cameroon and 448 deaths); the countries reporting with the greatest number of reported deaths included South Africa (29,577), Egypt (7805), Morocco (7485), Tunisia (4800) and Algeria (2772) .

Despite the ongoing efforts to manage the disease, no antiviral drug currently exists for the prevention or treatment (Shio-Shin et al. 2020) , and many months may be required for their development. There are actually a number of COVID-19 candidate vaccines for which certain national regulatory authorities have authorized their evaluation or use. However, none have yet received WHO authorization (Calina et al. 2020) . However, the spread of the COVID-19 pandemic is very dynamic and growing around the world. In response to this outbreak, the World Health Organization, on January 30, 2020 declared that the pandemic constitutes a public health emergency of international concern and issued temporary recommendations under the International Health Regulations.

Currently, no approved drug for COVID-19 exists and treatments provided worldwide to the affected persons are symptom based. These include antiviral drugs so far used against major groups of viruses like human immunodeficiency virus (HIV), herpes, hepatitis, influenza, SARS-CoV and MERS-CoV, antimalaria drugs, imunostimulants, antiinflammatory drugs that may be effective against elevated levels of cytokines and useful in inhibiting viral infection (Vellingiri et al. 2020) .

Reviews by Vellingiri et al. (2020) , Liu et al. (2020) and Wu et al. (2020) reported that the current most clinically used drugs can be grouped into three categories: antiviral agents, supporting agents and miscellaneous agents and therapies (Table 1) .

Worldwide, a number of drugs which have so far been proven to be safe for humans, are currently being repurposed to be used for the management of this disease.

The 2019 novel coronavirus genome encodes several structural proteins, including the glycosylated spike (S) protein that functions as a major inducer of host immune responses. This S protein mediates host cell invasion via binding to a receptor protein called angiotensin-converting enzyme 2 (ACE2) located on the surface membrane of host cells. Hence, the interaction between viral S protein and ACE2 on the host cell surface is of significant interest in the therapeutic response process since it initiates the infection process.

Globally, herbal treatments have been proven effective to control contagious disease during the 2003 severe acute respiratory syndrome (SARS) outbreak (Zhang et al. 2020) . Therefore, since the outbreak of COVID-19, there has been great attention in investigating metabolites secreted by plants that may be developed as medicines for Historically, traditional medicine and local beliefs have always played a role in epidemics through time (Zhang 1996) . A review by Jassim and Naji (2003) reported numerous potentially useful medicinal plants that need to be evaluated and exploited for therapeutic applications against genetically and functionally diverse virus families. Keyaerts et al. (2007) identified a variety of plant lectins as antiviral compounds against the SARS-CoV. Lelesius et al. (2019) also showed that some extracts of plants including Thymus vulgaris and Desmodium canadense were effective against avian infectious bronchitis virus, a highly contagious respiratory disease in chickens caused by a corona virus that belongs to the Coronaviridae family. From all over the world, people are witnessing a deep attachment to popular medicine to protect themselves against COVID-19. This is because to date, herbal products have proven to be not only effective, but also widely available to consumers.

Africa is endowed with diverse environmental conditions and a diversity of pathogenic microbial species (bacteria, fungi, and viruses). These microbes are causal agents of a great number of diseases (Cunningham et al. 2008) , thus suggesting that African plants could accumulate Adapted from Vellingiri et al. (2020) , Liu et al. (2020) and Wu et al. (2020) Drug name/category Description

Remdesivir A broad-spectrum antiviral agent, anti-viral peptide that was used in treatments against Ebola, SARS-CoV and MERS-CoV Hydroxychloroquine and Chloroquine An anti-malarial drug, which has been effective in the treatment of avian influenza A;

Can inhibit the entry of SARSCoV-2 and prevent virus-cell fusion by interfering with glycosylation of the ACE2 receptor and its binding with spike protein; Anti-viral and immune modulating properties; Can reduce cytokine storm Lopinavir-Ritonavir

Lopinavir is a protease inhibitor with high specificity for HIV1 protease Ritonavir inhibits the enzymes that are responsible for lopinavir metabolism, and its co-administration improves antiviral activity Lopinavir was also used along with another flu drug, oseltamivir and resulted in complete recovery of patients showing signs of COVID-19 related pneumonia Umifenovir (Arbidol)

A drug targeting S protein/ACE2, it is an inhibitor that may disrupt the binding of viral envelope protein to host cells, thus preventing viral entry to the target cell. It has been used earlier as influenza antiviral drug; An in vitro antiviral efficacy in widely spreading virus strains such as the Ebola virus, human herpesvirus 8 (HHV-8), hepatitis C virus (HCV), and Tacaribe arenavirus Favipiravir (Avigan)

A broad spectrum anti-viral drug, a purine nucleoside whose possible mechanism on COVID-19 is through its action as an alternate substrate leading to inaccurate viral RNA synthesis Oseltamivir (Tamiflu)

A drug approved for treatment of influenza A and B. It inhibits the spread of the influenza virus in the human body Ribavirin A broad-spectrum antiviral drug used in the treatment of hepatitis C, in combination with interferon α (IFN) Sofosbuvir A drug also used for the treatment of hepatitis C in combination with interferon or RBV Supporting agents Azithromycin An antibiotic used against many different types of infections caused by susceptible bacteria, It has been proven to be active in vitro against Zika and Ebola viruses and to prevent severe respiratory tract infections when administered to patients suffering viral infection Vitamin C (Ascorbic Acid) As a potent antioxidant agent, it neutralizes free radicals and helps to prevent or reverse cellular damage It has immunomodulatory activity An antiviral agent against influenza viruses Zinc Inhibits SARS-CoVand retrovirus RNA polymerase activity Enhances chloroquine intracellular uptake Corticosteroids Anti-inflammatory drug Prevent an extended cytokine response and may accelerate resolution of pulmonary and systemic inflammation in pneumonia Tocilizumab (Actemra) Immunosuppressive drug, emerged as an alternative treatment for COVID-19 patients with a risk of cytokine storms Sarilumab It inhibits IL-6 that might play a role in driving the inflammatory immune response that causes acute respiratory distress syndrome observed in patients with severe COVID-19 infection Interferon (IFN) Beta 1-Alpha) It has nonspecific antiviral as well as other complex effects on immunity and cell proliferation Miscellaneous Agents and Therapies Ibuprofen Activators of ACE2 receptors Indomethacin Antiviral activity against SARS-CoV and canine coronavirus (CCoV) chemopreventive substances more than plants from the northern hemisphere (Mahomoodally 2013) . Basically, more than 80% of the population in this continent is known to rely on traditional medicine for their primary health care needs. In Burkina Faso, the country's plan to respond to the COVID-19 pandemic does not rule out the use of herbal medicines, and clinical trials are underway on Apivirine, a phytomedicine from Benin which is alleged to be effective against the coronavirus (Sputniknews 2020).

In Algeria, to face the spread of this pandemic, consultation of herbalists in the search of traditional antiviral and anti-flu recipes have significantly increased (Le Point International 2020). Goothy et al. (2020) supported the possible role of medicinal plants in Ayurveda's medicine for the management of Corona virus disease . Sharma and Kaur (2020) showed that Jensenone from Eucalyptus essential oil was a potential inhibitor of 2019 corona virus.

In China, DU Hong-Zhi et al. (2020) argued that traditional chinese medicine is an effective treatment for the 2019 novel coronavirus pneumonia.

More recently, the Malagasy Institute for Applied Research developed an herbal tea based on Artemisia annua (COVID Organics), claiming preventive and curative properties against COVID-19 (Midi-Madagascar 2020) .

In China, herbal traditional medicine have been proven effective to control contagious disease during the 2003 severe acute respiratory syndrome (SARS) outbreak and a recent screening of a Chinese herbal medicine database have confirmed that herbal treatments classically used for treating viral respiratory infection contain chemical compounds that have potential anti-2019-nCoV activity (Zhang et al. 2020) .

In Nigeria, recent reviews on potential plants for treatment and management of COVID-19 have been carried out. The results presented up to a hundred Nigerian indigenous medicinal plants with therapeutic abilities which may serve as effective treatments for COVID-19 due to their antiviral, anti-inflammatory, antioxidant, antipyretic, immunomodulatory and cyto-protective properties (Oladele et al. 2020; Ikpa et al. 2020) .

In Cameroon, since the first case was reported in the country, several herbal recipes have been popularized in social media, as alleged solutions to manage COVID 19. According to a recent release from the Cameroon Radio and Television Corporation, the Archbishop of Douala, His grace Samuel Kleda, has made public an attempt at treating symptoms of COVID-19 with a herbal remedy, free of charge and the Ministry of Public Health is showing commitment to support the process of development and homologation of this treatment (Crtv 2020).

As the world is currently seeking treatment for COVID-19, there is an urgent need to boost up research so as to develop effective and affordable therapeutics.

In Cameroon, access to health care services is challenging. One out of every 1,000 patients is able to see a specialist and 3 out of 20 patients are able to buy prescribed drugs in hospitals (Kuete and Efferth 2010) . In this context, the COVID-19 situation is likely to worsen as the country moves into phase 2 of this pandemic marked by a shift from virus importation to intra-community transmission. Based on this situation, the Government prepared a COVID-19 Preparedness and Response Plan of US$600 million to respond to the crisis, under the leadership of the Ministry of Public Health and with the partnership of international organizations. This health response strategy has eight components:

• Multisectoral and international coordination, • Surveillance for early detection of cases, • Investigation and rapid intervention teams, • Laboratory capacities, • Infection prevention and control measures in hospitals and in the community, • Case management, • Risk communication and community engagement, and • Logistics.

Several treatment protocols including the Chloroquinebased treatment suggested by Professor Didier Raoult (Colson et al. 2020) are being tested with varying degree of effectiveness.

However, since the outbreak of this disease, ethnobotanical and ethnopharmacological research geared at bringing the potentials of traditional medical knowledge into the debate over the management of this disease has been lacking. Yet Cameroon is a biologically diverse country. This country is located in Central Africa, in the heart of the Congo Basin, the world's second largest rainforest after the Amazon. Its floristic potential scores more than 7850 plant species recorded at the national herbarium. This ranks Cameroon among the countries with the highest levels of biodiversity in Africa. Despite the inaccuracy of statistics, medicinal plants are important elements of health care services. However, access to such plants has so far been largely through traditional healers and herbal markets which are part of an informal economy. The huge volume of published research on medicinal plants in Cameroon surprisingly contrasts with the paucity of approved phytodrugs. Among the pressing challenges that must be tackled for acceptable use of traditional and alternative medicines in modern therapeutics in Cameroon are:

• the increasing use of traditional medicines and the general weakness in translating research into concrete drug discovery and development,

• the evolution of international regulations on access to genetic resources and the growing concern by stakeholders vis-à-vis the demands for patenting rights, evidence of safety, efficacy, good quality traditional medicinal products and a range of other ethical issues, • the shortage of essential infrastructure in both the public (universities and other governmental institutions) and private sectors, • the need for integrating and promoting the potential of medicinal plants as a source of health care. 

This review is part of the contribution of ethnobotany and ethnopharmacology sciences in the fight against COVID-19. It aims at providing a preliminary review of available literature on medicinal plants with potentials to be evaluated and developed for the management of COVID-19 in Cameroon. The findings of this review will provide other researchers with opportunities to identify the right medicinal plants to be evaluated from a perspective of developing new drugs to combat COVID-19.

The theoretical framework for the study is based on a 3-step review approach.

First, we acknowledge that the use of medicinal plants for the treatment of viral infections in our traditional societies is ancient. Meanwhile, COVID-19 is a novel disease and consequently not yet known in our traditional knowledge system on diseases. However, evidence from existing literature supports the management of symptoms similar to those of COVID-19 using a diversity of plant-based recipes. A recent review by Poudel Adhikari et al. (2020) presented the most commonly reported symptoms of COVID-19. Those considered in this review were: fever/malaria, runny nose, cough, myalgia or fatigue, body pains and sore throat. This review is based on the assumption that a plant that has been used to manage at least 3 common symptoms of COVID-19 is a potential source of anti-COVID-19 molecules.

Secondly, the inhibitory effect of some secondary metabolites from medicinal plants on the 2019 novel corona virus protease have been reported by Zhang et al. (2020) in China, Mohammadi and Shaghaghi (2020) in Iran and Khaerunnisa et al. (2020) in Indonesia. In this regard, the identification of Cameroonian medicinal plants with potentials as anti-COVID-19 was based on the investigations of their phytochemical profile to select those that are source materials for these secondary metabolites. Besides the metabolites cited by the above-mentioned studies, alkaloids are also a rich source of active components of plants that have already been fruitfully developed into various chemotherapeutic compounds comprising Chloroquine, an antimalarial drug reported to be effective for the treatment of COVID-19 and many other viral infections (Moradi et al. 2017; Colson et al. 2020; Gao et al. 2020) . The mechanism of the antiviral activity of alkaloids is based on the inhibition of replication of viruses. Hence, in this study, a plant known as an important source of alkaloid is also considered as potential anti-COVID-19. Similar bioactivity on 2019-nCov was also reported for hydrolysable tannins, natural polyphénols (Khalifa et al. 2020; Adem et al. 2020) and terpenoids (Shagaghi 2020). Therefore, we also consider of great potential for COVID-19 management, plants that are rich sources of these secondary metabolites.

Thirdly, the use of biologics that stimulate immune responses was suggested by Zumla et al. (2020) as a way to help patients resist the invading virus. There is an abundant literature reporting the use of plants by traditional medicine practitioners to boost the immune system in people living with HIV/AIDS (Anywar et al. 2020) . In addition to the important role of boosting the immune system, evidence from the literature reveals the importance of antimalaria and antiviral drugs in the global therapeutics against COVID-19 (Vellingiri et al. 2020) . This is also the case for antiinflammatory drugs that may be effective against elevated levels of cytokines and useful in inhibiting viral infection. Hence, plants with immunostimulant, antiviral, anti-malaria and anti-inflammatory properties are considered in this study as of great potentials for COVID-19 management.

This review is based on data available in published literature. Bibliographic information on medicinal plants was searched in several databases including: Google Scholar, PubMed, Scopus, ScienceDirect, Researchgate, PROTA, GLOBEinMED, to retrieve all relevant papers. Key words used included among other, the symptoms of COVID-19 (fever/malaria, runny nose, cough, myalgia or fatigue, body pains and sore throat), immunostimulant, antiviral, antimalaria, anti-inflammatory, and secondary metabolites with confirmed inhibitory effect on the 2019 nCov (Allicin, Apigenin-7-glucoside, Catechin, Coumaroyltyramine, Curcumin, Desmethoxyreserpine, Diosmin, Epicatechin-gallate, Gingerol, Hesperidin, Kaempferol, Lignan, Luteolin-7-glucoside, Naringenin, Oleuropein, Pedunculagin, Punicalin, Quercetin, N-cis-feruloyltyramine, etc.).

A total of 119 papers were reviewed including books, journal articles, proceedings, preprints. The reference lists of some research articles were exploited to explore additional relevant studies. The database of the Global biodiversity Information Facility (GBIF) was searched to confirm the occurrences and distribution of the plant species recorded.

From the ethnobotanical and ethnomedical literature consulted, plants were selected and recorded based on their uses (focus on plants used to treat symptoms of COVID-19), their phytochemical composition (with a focus on plants rich in alkaloids, tannins, terpenoids and phenolics), their pharmacological activity (focused on plants with anti-inflammatory, immunomodulatory, antimalarial and anti-viral properties). All the plant species recorded were compiled in an Excel database.

The documented uses of each plant, the presence or absence of the targeted secondary metabolites and their documented pharmacological activity were used to generate a new data set which was analyzed by principal component analysis (PCA) to detect cluster formatting and the patterns of variability present in the data sets of the medicinal plant species recorded.

The main protease (Mpro)/chymotrypsin like protease (3CLpro) from the 2019 novel corona virus, is reported to be a potential target for the inhibition of its replication (Lu, 2020) . Khaerunnisa et al. (2020) showed that luteolin-7-glucoside, demethoxycurcumin, apigenin-7-glucoside, oleuropein, curcumin, catechin, and epicatechin-gallate appeared to have the best potential to act as COVID-19 Mpro inhibitors. Faheem Khan et al. (2020) showed that epigallocatechin gallate (EGCG), a major constituent of green tea (Camelia sinensis), was the lead compound that could fit well into the binding sites of docked proteins of SARS-CoV-2 and recommended this molecule as a drug candidate for the treatment of COVID-19. Mohammadi and Shaghaghi (2020) reported that secondary metabolites including kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, epicatechin-gallate, zingerol, gingerol, and allicin were potential inhibitor candidates for COVID-19 Mpro, with Curcumin showing the strongest interaction with the protease enzyme of COVID-19. A recent study by Zhang et al. (2020) has identified several Chinese medicinal plants classified as antiviral/antipneumonia-effective that directly inhibit the novel coronavirus, 2019-nCoV. The metabolites tested for this bioactivity were Betulinic acid, Coumaroyltyramine, Cryptotanshinone, Desmethoxyreserpine, Dihomo-c-linolenic acid, Dihydrotanshinone, Kaempferol, Lignan, Moupinamide, N-cis-feruloyltyramine, Quercetin, Sugiol, Tanshinone IIa. Khalifa et al. (2020) showed that the Pedunculagin, tercatain, and punicalin, three hydrolysable tannins, successfully inhibit the protease enzyme of 2019 novel Corona Virus. Adem et al. (2020) evaluated the efficacy of medicinal plant-based bioactive compounds against COVID-19 Mpro by a molecular docking study. They concluded that natural polyphénols including hesperidin, rutin, diosmin, apiin,

prop-2-en-1-one, and β,β'-(4-Methoxy-1,3 phenylene)bis(2′-hydroxy-4′,6′-dimethoxyacrylophenone were effective inhibitors of this new Corona Virus.

From the research conducted by these authors, it is clear that Cameroonian medicinal plants can provide source materials for these secondary metabolites. The review of the phytochemical screening done on Cameroonian medicinal plant species shows that 32 species native or naturalized in Cameroon are source materials for most of the above-mentioned secondary metabolites (Table 1 ). There is also evidence from available literature indicating diverse pharmacological properties for these species including antimicrobial, antiviral, analgesic, anti-inflammatry, antipyretic, antioxidant, and more. (Table 2 ). Besides Curcumine from turmeric (Curcuma loonga), some of those local plant species are interesting as they contain many of those active secondary metabolites. This is the case of Zanthoxyllum heitzii containing both Apigenin-7-glucoside and Oleuropein, and Citrus spp, a rich source of Diosmin, Lignan, Naringenin and Quercetin that showed high inhibitory effect on 2019 corona virus.

The review yielded a total of 230 medicinal plants of potential for the management of COVID-19. From this general list 

Strong antimicrobial activity Mohammadi and Shaghaghi (2020) , Borlinghaus et al. (2014) Stimulates the activity of immune cells, Inhibits the release of TNFα-dependent pro-inflammatory cytokines Inhibits the migration of neutrophilic granulocytes into epithelia, which is a crucial process during inflammation Apigenin-7-glucoside, Zanthoxyllum heitzii exerts inhibitory effect on HL-60 cells through the reactive oxygen species (ROS) generation, loss of mitochondrial membrane potential and cell cycle destabilization Mohammadi and Shaghaghi (2020) , Khaerunnisa et al. (2020) , Pieme et al. (2014) Catechin Khaya grandifoliola n -hexane extract, crude and purified fractions are active antimalarial activities Mohammadi and Shaghaghi (2020) , Khaerunnisa et al. (2020) , Agbedahunsi et al. (1998) contains ingredients that showed invitro activity against hepatitis C virus 

Camellia sinensis Regular consumption of green tea decreases influenza infection rates and some cold symptoms, and gargling with tea catechins may protect against the development of influenza infection Mohammadi and Shaghaghi (2020) , Faheem Khan et al. (2020) , Khaerunnisa et al. (2020) , Isemura (2019) Laportea aestuans Antimicrobial effect of crude extract Mambe et al. (2016) (2020), Mehdi Sharifi-Rad et al. (2017) Hesperidin Acacia senegal Used in the management of cough

Mahomoodally (2013) Laportea aestuans Antimicrobial effect of crude extract

Increases antioxidant defenses, scavenges reactive oxygen species, modulates immune system activity Mohammadi and Shaghaghi (2020) , Salehi et al. (2019) Dose-dependent inhibitory effect against dengue virus, prevents intracellular replication of chikungunya virus, and inhibits assembly and long-term production of infectious hepatitis C virus particles in a dose-dependent manner of plants recorded, 90 species were selected for being mentioned as used to manage at least 3 symptoms of COVID-19, and the remaining species were excluded (Table 4) . These 90 species belong to 53 botanical families. The families with the greatest number of representatives are Rubiaceae (8 species), Asteraceae and Euphorbiaceae (6 species), Caesalpiniaceae and Meliaceae (5 species), Solanaceae (4 species), Apocynaceae, Combretaceae, Malvaceae, Sapotaceae and Verbenaceae (3 species). The greatest number of citations was recorded for three of the six symptoms investigated: fever/malaria, cough and myalgia/fatigue (Table 3) .

Various plant parts are used in the different treatments reported in the literature. However, leaves, fruits and bark were the most used parts, indicating that their utilization may not severely affect the sustainability of the resource base (Fig. 1) .

Available data on the phytochemical screening of these selected species shows that the most distributed secondary metabolite in this selected sample of plants was alkaloids (36%) (Fig. 2) . Previous studies by Ntié-Kang et al. (2013) also confirmed the greater distribution of terpenoids (26%), flavonoids (19.6%) and alkaloids (11.2%) in Cameroon's medicinal plants. (2020), Mohammadi and Shaghaghi (2020, Zhang et al. (2020) , Khalifa et al. (2020) and Adem et al. 

Evidence from research conducted on SARS-COV and COVID-19 shows that the weakening of the immune system is one of the major contributing factors to the increased incidence of COVID complications like pneumonia and mortality in affected patients (Curbelo et al. 2017; Taghizadeh-Hesary and Akbari 2020; Prompetchara et al. 2020) . These authors argued that improving the immune system response may be effective in reducing the incidence of pneumonia, and reduction of inflammation may be effective in reducing the mortality rates due to pneumonia. From the literature data compiled, about 10 species have been documented for their beneficial effect in boosting the immune system. Among these species, 3 were also cited to treat at least 3 symptoms of COVID-19: Azadirachta indica and Momordica charantia and Vernonia amygdalina ( Overall, the leaves, bark and roots are the most used plant parts as noted below (Fig. 3) .

Overall, these species belongs to 53 different botanical families. The families with a higher number of representatives are Caesalpiniaceae (10 species), Asteraceae (3 species), Cucurbitaceae and Apocynaceae (3 species), Euphorbiaceae, Lamiaceae, Meliaceae, Acanthaceae, Combretaceae, Euphorbiaceae, Meliaceae and Mimosaceae (2 species). Of the 230 species recorded, 102 are already documented for their traditional use to manage at least 3 common symptoms of COVID-19. The PCA analysis separated 4 groups of medicinal plant species with axis 1 and 2 explaining 65.7% of the variability within the sample (Fig. 4) .

The first group consists of plants treating at least three symptoms of COVID 19, containing key phytochemicals reported as being of interest for COVID management (alkaloids, phenolics, tannins and terpenoids) and having antimalaria properties. Representative species include Abelmoschus esculentus, Artemisia annua, Capsicum annun, Curcuma longa, Eucalyptus camaldulensis, Eremomastax speciosa, Kalenchoe crenata, Lippia multiflora, Morinda lucida, Senna alata, Solanum torvum, etc.

The second group consists of highly promising species like Azadirachta indica, Harungana madagascariensis, Mangifera indica, Momordica charantia, Picralima nitida, Trichilia emetica. This consists of plants used to treat COVID-19 symptoms which, at the same time are sources of the key phytochemicals and also have relevant pharmacological activities (antiviral, anti-inflammatory, immunostimulant, or containing secondary metabolites with confirmed anti-SARSCOV2 activity). Even when used alone, they can be evaluated and developed as potential remedies, while the other species may be used in association to each other for their complementary effects.

The third group consists of potential anti-malaria agents based on the species Allium sativum, Psidium guajava, Phyllanthus muellerianus, Occimum gratissimum, Stereospermom acuminatissimum, etc. The fourth group consists of immunostimulants, antiinflamatory, antiviral agents and plants containing some secondary metabolites with confirmed anti-COVID-19 properties, with representative species like Moringa oleifera, Panda oleosa, Tapinanthus globuliferus, Zanthoxyllum heitzii, and Vernonia amygdalina.

Overall, the recorded medicinal plant species offers an array of possibility of using individual species or combinations of species for their complementary effects, based on the clinical symptoms showed by the patients and the therapeutic objective to be achieved.

In developing countries with poor access to health facilities like Cameroon, medicinal plants are the richest and most available sources for use and even for drug discovery. In such situations when our societies are desperate to discover cures for new and deadly disease like COVID-19, the contribution of herbal medicine in early response strategies should be promoted. Though the country's pharmaceutical potentials are immense, constraints and challenges however exist at all levels. To effectively address these shortcomings, a strong political-will and support of the Cameroonian government will be crucial.

Research in ethnobotany, ethnopharmacology and bioactive components of medicinal plants of Cameroon has been ongoing for quite some time by University laboratories, by the Institute of Medical Research and Medicinal Plants Studies (IMPM) and by independent researchers. However, a systematic and concerted approach to this activity has been lacking. Much of this research has been academic and the concept of applied research in plant-based drug development has not received much attention. Although enough has been done in propagation of medicinal plants, research in support of industrial development, appropriate processing technologies to improve quality and yield, new formulations to new products and the marketing of finished products is still poorly developed. Actually, many medicinal plants sourced from Cameroon were involved in patents, most of which are owned by foreign entities (Oldham et al. 2013) .

Capacity building and financial support are a necessity at all level in order to stimulate active research on natural medicinal products at the local level. Specifically, efforts have to be geared towards developing and sponsoring applied research on natural products and drug discovery. It is indeed paradoxical that with the country's medicinal plant potentials, herbal drug discovery has not yet reached the expected performance.

One of the main problems facing the use of herbal medicines is the proof requirement of their usefulnes, safety and effectiveness. Unfortunately, research and training activities for traditional medicine practitioners have not received due support and attention. As a result, the quantity, quality, safety and efficacy of herbal preparations are far from sufficient to meet demand. These weaknesses could be corrected by capacity building and low-cost technologies for the industrial production of traditional medicines to make them more effective, stable, reproducible, controlled, and in galenic forms that can easily be transported. Capacity building will be vital for also organizing the stakeholders and integrating their practices into the perspectives of modern research and development continuum. By so doing, the indiscriminate sale and advertisement of herbal products in all forms of media without compliance to the existing regulations would be discouraged. 

In the face of the current risk of deforestation and degradation, conservation of medicinal plants must be a central focus. In this regard, one of the challenges is the lack of a complete and conserved knowledge repository on the national pharmacopoeia and the immense medicinal metabolite diversity among these plants. Such a repository will be vital in providing the scientific community with comprehensive knowledge about metabolite diversity and exploitation in early response strategies for emerging diseases. Because of the growing environmental degradation and the rapid loss of the natural habitat for some of these plants due to anthropogenic activities, it is becoming increasingly urgent to reinforce medicinal plants conservation and documentation of their uses.

To ensure the sustainability of the resource base and to address potential risk of overexploitation that may result from excessive commercialization and unsustainable practices, conservation measures for medicinal plants will also be required. The effectiveness of the future sustainability of local natural ecosystems that harbour these medicinal plants will depend upon conservation management approaches that value the importance of involving local communities. In this light, there are lessons learned from Prunus africana management in the Mount Cameroon area that can fuel our steps forward in the establishment of such a medicinal plant conservation strategy.

The ratification by Cameroon of the Nagoya protocol on access to genetic resources and benefit sharing opens new and promising avenues to achieve the objectives of 

conserving local medicinal plants, ensuring their sustainable utilization and improving their contribution in livelihoods improvement and economic development.

There has so far been only very poor participation of the local private pharmaceutical industries in the field of herbal drug development in Cameroon. There should be incentives developed to attract and stimulate their investment in traditional medicine research, development and commercialization.

The purpose of this stock-taking study was to provide a preliminary review on Cameroonian medicinal plants with the potential to be evaluated and developed as remedies for the management of COVID-19. It appears that the country's medicinal plants potential is immense and a promising resource from a perspective of novel drug development against this pandemic. Based on the present findings it can be concluded that medicinal plants can be promising resources for the management of COVID-19 in African herbal medicine in general and Cameroon in particular.

Despite the great potential of local medicinal plants, it is unfortunate that they are still pejoratively refered to as "grand-mother recipes". More than ever, there is a need for applied research to provide more scientific evidence for the efficacy, to establish the standard formulation using the preliminary check list presented in this review and further clinical studies as part of the response strategy for the management of COVID-19.

Funding The authors declare that they did not receive any funding for carrying out this research. 

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Šalomskas A (2019) In vitro antiviral activity of fifteen plant extracts against avian infectious bronchitis virus

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Kuete V (2016) Antibacterial activities of methanol extracts from Alchornea cordifolia and four other Cameroonian plants against MDR phenotypes

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The authors are grateful to Carol J. Pierce Colfer (Center for International Forestry Research in Bogor, Indonesia and Cornell University in Ithaca, New York, United States of America) for the valuable comments during the writing of the paper and for proofreading the final manuscript.