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Antiviral medicinal plants -

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Phytother Res 21 10 — Bonvicini F, Lianza M, Mandrone M, Poli F, Gentilomi GA, Antognoni F Hemidesmus indicus L. extract inhibits the early step of herpes simplex type 1 and type 2 replication.

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Int J Pharm Pharma Sci — Edziri HÁ, Smach MA, Ammar S, Mahjoub MA, Mighri Z, Aouni M, Mastouri M Antioxidant, antibacterial, and antiviral effects of Lactuca sativa extracts. Ind Crops Prod 34 1 — Lipipun V, Kurokawa M, Suttisri R, Taweechotipatr P, Pramyothin P, Hattori M, Shiraki K Efficacy of Thai medicinal plant extracts against herpes simplex virus type 1 infection in vitro and in vivo.

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Unfortunately, these synthetic drugs have been reported to produce countless adverse effects. In some cases, they may become ineffective on emerging viral resistant strains Kurokawa et al. Keeping in view the global burden of viral infections as well as medication cost, there is an urgent need to develop new strategies to search for affordable and effective antiviral drugs.

Ethnopharmacology has contributed immensely to the development of phytotherapeutics and the discovery of new drugs Heinrich and Gibbons, In recent time, medicinal plants and their bioactive metabolites have become one of the main focuses of interest to search for effective as well as affordable drugs to cope with the current necessities Perera and Efferth, Traditional herbal medicine from indigenous origin has an ancient history of curing numerous chronic and infective diseases.

Hence, the quest for novel antiviral agents focuses not only on synthetic combinations but also on the plant-derived metabolites.

A variety of plant metabolites can impede viral replication without affecting the host physiology or with limited side effects Martin and Ernst, ; Hussain et al. Along with direct interferences to viral replication process, these natural products may exhibit potentiality to modulate the immune responses of host against viral infections Kurokawa et al.

Researchers have reported that numerous medicinal plants with antiviral activities, such as Andrographis paniculata , Lindera chunii , Dioscorea bulbifera , Wistaria floribunda , Xanthoceras sorbifoli, and Aegle marmelos showed remarkable anti-HIV activity Kaur et al.

Moreover, a number of natural or plant-derived compounds belonging to different chemical groups have been reported for their potential anti-HBV activities Chou et al. There is much to gain and learn about remedial qualities of plants from the pre-existing knowledge of traditional medicines that may be evaluated for various applications as potential antiviral drugs.

It is convenient to find plants that can be researched upon; however, what is required is the traditional knowledge that must be translated into pharmaceutical application in formulating novel drugs, finally taking it from the laboratory bench to the bedside.

Even though numerous medicinal plants as well as plant derived metabolites have been reported for their antiviral effects, there lacks adequate combined substantial reports of pre-existing researches with mechanistic insights Martin and Ernst, In most of the cases, due to lack of any substantial compilation report, the researchers conducted the similar studies as preliminary screening prior to design the advanced stages of discovery of potent drug molecule from plant.

This is a complete loss of time, money and efforts. Only literatures written in English language were considered due to language barrier.

In this review, studies covering following types of data were included and extracted: medicinal plants with antiviral activity along with their distribution, availability, traditional and folklore use, in vitro and in vivo studies of plant extracts and isolated bioactive compounds, their structural activity relationship and mechanism of antiviral activities.

The focus of this review was on potential antiviral metabolites indigenous to and cultivated in Bangladesh. Due to lack of adequate scientific data regarding antiviral activities of medicinal plants collected from Bangladesh, available studies conducted on similar plant species in different countries are considered.

A total of 46 antiviral plants from 25 families were substantiated in Table 1. According to families, medicinal plants were categorized. About 36 bioactive metabolites with significant effects and their underlying mechanisms of these antiviral activities were summarized in Table 3.

TABLE 1. Overview of the effects of medicinal plants extracts on common viral infections. Acanthus ilicifolius L.

belonging to family Acanthaceae, is a mangrove plant with numerous medicinal properties, including anti-inflammatory, antioxidant and hepatoprotective activities. This medicinal plant exhibits potent antiviral activity against hepatitis B virus. A study performed on duck model revealed that alcoholic extract of whole plant is capable of reducing the viral load by interfering DNA replication, but the exact mechanism was not explained well Wei et al.

Andrographis paniculata Burm. Nees belongs to Acanthaceae family as well. It possesses excellent neutralizing activity against the human immunodeficiency virus HIV.

Andrographolide is a phytochemical isolated from this plant which has been reported for antiviral activity against herpes simplex virus HSV , HIV, flaviviruses, and pestiviruses Jayakumar et al. Besides, this bioactive compound has been reported for inhibition of the expressions of HSV-I viral envelope glycoproteins D and C Wiart et al.

This compound is now under clinical trial phase-IV for treatment of bronchitis Table 2. Justicia adhatoda L. is another member of Acanthaceae family which is native to Bangladesh. It is known as malabar nut, adhatoda or vasaka and traditionally used in cold, cough and respiratory disorders from ancient times.

Methanolic extract of the leaves of this medicinal plant has been reported for inhibitory activities against influenza and herpes simplex virus HSV. Six alkaloids namely vasicoline, vasicolinone, vasicinone, vasicine, adhatodine and anisotine have been isolated from the leaves of J. In silico bioassay demonstrated that anisotine has significantly inhibited the main protease Mpro of SARS-CoV Mpro mediates the cleavage of polyprotein to get matured and acquire infectivity.

The assay has also suggested that inhibitory potential of this alkaloid is higher compared to the inhibitory activities of lopinavir and darunavir established antiviral drugs Ghosh et al.

Achyranthes aspera L. belonging to the family Amaranthaceae, is a medicinal plant of the Garo tribe population in the Madhupur forest region of Bangladesh. It is a well-known folk medicine not only in Bangladesh but also in Indian subcontinent. It contains a potent antiviral compound named oleanolic acid which has been reported to work against herpes simplex virus type-I, HSV-I EC 50 6.

Both the plant extract and oleanolic acid inhibited the early stage of multiplication, specifically 2—6 h of post infection of the viruses. Allium sativum L. In Bangladesh, it is cultivated all over the country as a fundamental spice used in cooking. A study has been documented that various extracts of A.

sativum have inhibitory activities against adenovirus-3 ADV-3 , adenovirus ADV Khanal et al. Numerous antiviral phytocompounds have been isolated from a number of extracts of the bulb of A. sativum including ajoene, allicin, alliin, allyl methyl thiosulfinate, allitridin, diallyl sulfide, garlicin, and lectins.

It also inhibits viral attachment to host cell and reverse transcriptase of HIV-I. Apart from these, it induces apoptosis of HCMV infected cells.

Allicin and allyl methyl thiosulfinate inhibit the entry of HSV-I and II, PIV-3, VV, VSV and HRV-2 by disrupting viral envelope and cell membrane.

Alliin, diallyl sulfide, and garlicin work against DENV by diminishing inflammation through suppressing oxidative stress. Allitridin has excellent multiple effects against HCMV. The underlying mechanisms of these activities include inhibition of viral DNA synthesis by interfering viral immediate-early antigen expression, inhibition of viral replication by suppressing viral IEG gene transcription, and enhancement of Treg expansion and Treg-mediated anti-HCMV immunosuppression Alejandria, ; Wang et al.

Mangifera indica L. is one of the most common plants for fruit considering as the king of all fruits in Bangladesh. It belongs to the family Anacardiaceae. This fruit is packed of antioxidants and other nutritious biomolecules.

The plant extract has been reported for its activity against influenza virus. Apart from this, it contains a bioactive compound named mangiferin having potential efficacy for inhibiting the duplication of HSV-I and antagonizing the cytopathic effects of HIV Al-Rawi et al.

Alstonia scholaris L. This plant is a rich source of total alkaloids having remarkable anti-inflammatory and antiviral activities. A study demonstrated that the total alkaloids present in this plant exhibited efficacy to fight against IAV. The mechanism of this antiviral activity involves inhibition of viral replication in A cells and Uderived macrophages , reduction of cytokine and chemokine generation at the mRNA and protein levels, as well as interfering the activation of pattern recognition receptor PRR - and IFN-activated signal transduction in A cells.

Along with these, increment of survival rate and reduction of the viral titer were observed in lethal PR8 mouse model Zhou et al. Another important species of Apocynaceae family is Calotropis gigantea L. Among them, the lignin glycoside was efficacious against H 1 N 1 strain of both of the subtypes A and B IC 50 value of Aloe vera L.

is a well-known medicinal plant belonging to Asphodelaceae family and found almost everywhere in Bangladesh. vera gel 0. This study has demonstrated that the gel is effective as topical treatment option for oral HSV-I infection Rezazadeh et al.

An in silico study revealed that treatment with ethanolic extract of A. vera significantly reduces of the replication of IAV along with inhibition of viral matrix protein 1 M1 , matrix protein 2 M2 , and hemagglutinin HA mRNA synthesis, and expressions of viral protein M1, M2, and HA.

Numerous potent antiviral bioactive compounds, such as quercetin, catechin hydrate, and kaempferol were isolated which have inhibited IAV H1N1 or H3N2 induced autophagy, M2 viral mRNA synthesis, and M2 protein expression. Apart from these, in silico docking simulation study stated that these bioactive compounds have higher binding affinity for M2 protein compared to established M2 protein inhibitors Choi et al.

Recently, COVID pandemic has created worldwide burden because of the unavailability of the suitable medical treatment option. Quercetin is under clinical trial for prophylaxis as well as management of the symptoms of this infection Table 2. Furthermore, A. vera has been reported to contain 9-dihydroxylO- z -cinnamoylmethoxy-aloesin, aloeresin and feralolide which showed potential to inhibit the main protease 3CLpro responsible for the replication of SARS-CoV-2 in an in silico investigation.

Eclipta prostrata L. is the only known member of Asteraceae family which has strong antiviral property. In Bangladesh, this valuable medicinal plant grows wildly in fallow lands and the cultivators consider them as weed.

This plant is known as kalo keshi and used as folklore medicine to treat snake bite and blood borne hepatitis. Coumestan is a phytosterol found in this plant which has been reported for excellent inhibiting activity against NS5B protein of HCV.

This protein is essential for viral RNA replication Kaushik-Basu et al. Therefore, this compound and its analogs might be targeted for development of novel replication inhibitors of HCV. Bombax ceiba L. It is also known as cotton tree because of producing cotton from flowers.

This flavonoid glycoside has been reported for having inhibitory activity on respiratory syncytial virus RSV Zhang et al.

This protein is crucial for expression of a cation-selective channel which regulates viral release mechanism Schwarz et al.

Anogeissus acuminata Roxb. ex DC. ex Guillem. This plant produces two dibenzylbutadiene lignans, namely anolignan A and anolignan B which showed significant inhibitory activity against HIV-I reverse transcriptase RT enzyme. Besides, both of the phytocompounds exerted a synergistic activity against this enzyme El-Ansari et al.

Cyperus rotundus L. belonging to family Cyperaceae, is considered as a troublesome and economically damaging weed found in almost all the croplands in Bangladesh. Surprisingly, this plant has numerous medicinal properties, including antidiarrheal, antioxidant, anti-inflammatory, antimutagenic, antiperiodic, anticonvulsant, anti-saturative, antipyretic, antifungal, antidiabetic, antimalarial, antilipidemic, antibacterial, antiviral, anti-tumoral, cardioprotective, and wound-healing properties Peerzada et al.

A study demonstrated that essential oil extracted from the rhizomes of this plant has inhibitory activity against HAV, HSV-I, and CVB. Humulene epoxide and caryophyllene oxide were identified as major bioactive compounds from this essential oil Samra et al. Caryophyllene oxide has been reported to exhibit very potent inhibitory activity against HSV-I which might be a prime lead for development of topical therapeutic agent to treat recurrent infection caused by HSV-I Astani et al.

Moreover, an in silico study demonstrated that humulene epoxide has remarkable binding affinity to four target proteins, such as spike glycoprotein, papain-like protease PLpro , 3-chymotrypsin-like protease 3CLpro , and RNA-dependent RNA polymerase RdRp which are crucial for regulation of lifecycle of SARS-CoV-2 Amparo et al.

Albizia procera Roxb. It is very popular traditional medicinal plant whose bark decoction is used to manage rheumatism, hemorrhage, and stomach-ache Sivakrishnan and Swamivelmanickam, This plant has potent antiviral activity against IAV.

A study showed that ethanolic, ethyl acetate, aqueous and hexane-chloroform extracts of the bark of A. procera have inhibited the integrase enzyme of IVA with IC 50 value of Butea monosperma Lam.

In Ayurvedic, Unani and Homeopathic medicine, this plant has numerous medicinal uses. However, scientific literature demonstrated that aqueous extract of various parts of this plant like bark, flowers, fruit, leaves, and roots showed significant inhibition of EV BrCr Panda et al.

Flacourtia indica Burm. is a tropical species of family Flacourtiaceae with broad geographical distributions covering Bangladesh. It is an edible wild fruit species used by the traditional medical practitioners for treating snakebite. This medicinal plant has been reported for inhibitory activity against chikungunya CHIKV and dengue DENV viruses.

Ethyl acetate extract of stem bark of this plant has inhibited CHIKV. Swertia angustifolia var. pulchella D. Don Burkill belonging to the family Gentianaceae, is a medicinal plant of Bangladesh which is mainly distributed in the mountainous regions.

It is known as Ayurvedic herb and is usually used to treat malaria and diabetes. Besides, local populations use this herb as folklore medicine to manage hepatitis, inflammation, and digestive disorders. Crude extract of this herb has been reported for exhibiting activity against HSV-I Verma et al.

Species of this genus exhibit numerous medicinal properties and have been used from ancient time as folklore medicines. The genus is actually the biggest sources of antiviral phytocompounds Tshilanda et al.

About 8 species of this genus are found in Bangladesh, namely Ocimum tenuiflorum L. which have been reported extensively for diverse antiviral activities. This medicinal plant is found almost every yard of people in Bangladesh. It produces a number of antiviral bioactive compounds, such as ursolic acid, eugenol, 1,8-cineole, and rosmarinic acid which exhibit potential to inhibit HSV-I and II Caamal-Herrera et al.

basilicum , known as sweet basil, contains 1,8-cineole, camphor, thymol, eugenol, eugenol epoxide, apigenin, linalool, and ursolic acid which have been reported to work against HIV-I, HSV, ADV-3, 8, 11, HVB, EV, and CVB-I Behbahani et al.

gratissimum is an aromatic herb which is commonly known as African basil. Essential oil of this basil leaves contains two alcohols namely eugenol and thymol.

Eugenol inhibits replication of HSV-I and II while thymol destructs the virion of HSV-I Benencia and Courreges, ; Maria das Graças et al. β-caryophyllene and 1,8-cineole have been isolated from O.

campechianum which exhibit anti-HSV-I and II activities as well as inhibit infectious bronchitis virus IBV Maria das Graças et al. americanum , recognized as American basil, is a medicinal plant which can produce essential oils and found in Bangladesh. Rosmarinic acid and oleanolic acid are the essential oils isolated from this herb.

Oleanolic acid inhibits HIV-I protease whereas rosmarinic acid inhibits internal ribosome entry site of EV Aluko et al. africanum produces caffeic acid which inhibits the multiplication HSV-I. Beside, linalool has also been isolated from the essential oil of this medicinal plant havinganti-ADV activity Romeilah et al.

forsskaolii is known as wild Amazonian basil which produces ursolic acid which exhibits anti-HCV activity. Moreover, O. carnosum showed anti-HSV-I and II activities due to presence of trans-anethole which inhibits multiplication of HSV-I and II Tshilanda et al.

Azadirachta indica A. This medicinal plant has a lot of medicinal properties and so, has been used for health management from ancient time in folklore, Ayurvedic, and Unani medicinal systems.

indica bark remarkably blocked the entry of HSV-I into host cells. Virucidal activity against CVB-B4 was observed by the extract of A. indica leaves Alzohairy, Gedunin and pongamol are the antiviral biocompounds extracted from A. indica having activity against DENV. Gedunin showed significant binding affinity to NS3 RNA polymerase and NS3 protease helicase mediate the synthesis of DENV proteins and genetic materials in the host cell as well as capsid and envelope proteins required for entry of DENV into host cells Rao and Yeturu, Melia azedarach L.

is another antiviral medicinal plant from Meliaceae family which has been reported for inhibitory activities against vesicular stomatitis VSV and HSV-I. A meliacarpin named limonoid 1-cinnamoyl-3,dihydroxymeliacarpin has been isolated from ethyl acetate extract of the leaves of this plant which showed inhibitory activities against VSV IC 50 values of 6 μM and HSV-1 IC 50 values of 20 μM Alché et al.

Ficus religiosa L. belongs to the family Moraceae which is used in traditional Ayurvedic and Unani medicines for healing cough, wheezing and asthma as well as sexually transmitted infections like gonorrhea and genital ulcers.

This medicinal plant exhibits numerous antiviral activities. A study demonstrated that ethanolic extract of the bark of F. religiosa inhibited Human rhinoviruses HRV EC 50 value: 5.

Aqueous extract showed inhibitory activity against respiratory syncytial virus RSV EC 50 value: 2. Another study stated that aqueous and chloroform extracts of bark were active against HSV-II and acyclovir-resistant strain.

The underlying mechanism of the aqueous extract involved direct inactivation of viral activity whereas chloroform extract suppressed the attachment and entry of virus to host cell membrane along with inhibition of viral progeny formation Ghosh et al. Artocarpus genus is another source of antiviral medicinal plant species.

Artocarpus integer Thunb. Zorn Fosberg are the species of this genus which have antiviral activity. integer has been reported to have activity against rotavirus simian rotavirus, SA11 and human rotavirus, HCR3 strains Gonçalves et al. Another study showed that dichloromethane extract of the leaves of A.

heterophyllus showed strong anti-HCV IC 50 value: 1. altilis and A. camansi showed moderate anti-HCV activities IC 50 values: 6. The underlying mechanism of such potent anti-HCV activity of A.

heterophyllus involved synergistic effects such as direct virucidal activity inhibition of viral entry and inhibition of replication of RNA and expression of viral protein at higher concentration Hafid et al. Phyllanthus niruri L.

This plant possesses antiviral activity as well. Aqueous extract of whole plant has been reported to inhibit endogenous DNA polymerase of HBV and woodchuck hepatitis virus WHV Tan et al. Another study stated that ethanolic extract of P.

niruri has Anti-HCV activity IC 50 value: 4. Apart from this, it showed synergistic activity 4-fold with an established drug, a NS3 protease inhibitor named simeprevir. Phyllanthin and hypophyllantin have been identified from this plant which showed binding to a protein, 4GAG required for entry of HCV to host cells in a in silico molecular docking assay Wahyuni et al.

Piper longum L. and Piper nigrum L. are the two most common species of Piperaceae family which are cultivated in Bangladesh as spices of cooking. Both of these species exhibit a number of medicinal properties and thus, are used as folklore and traditional medicines from primordial times.

Seeds of these medicinal plants have been reported for inhibitory activities on vesicular stomatitis indiana virus VSV-IN and human para influenza virus PIV Priya and Saravana Kumari, longum contains piperine which is a potent anti-HBV compound functioning against the secretion of HBsAg Selectivity Index, SI: Furthermore, P.

nigrum contains guaiol which has been reported by an in silico study to possess inhibitory potential to 6LU7 and 7JTL crucial targets of coronavirus Pandey et al. Cynodon dactylon L. is a non-toxic and edible grass belonging to Poaceae family which is known as durva grass or Bermuda grass It is found all over the countryside of Bangladesh and used as expectorant, emetic, laxative, coolant, analgesic, aphrodisiac, alexipharmic, emmenagogue, and so others.

This medicinal plant is very effective against bovine coronavirus infection BCoV which functions by inhibiting protease enzyme. As this viral strain has some common features with SARS-CoV and SARS-CoV-2, it can be used as dietary intervention of COVID Nalanagula, Rosa centifolia L.

The leave of this plant has antiviral activity. Methanolic extract of the leaves of R. centifolia L showed anti-HIV activity Palshetkar et al. Hedyotis scandens Roxb.

is a medicinal plant of Rubiaceae family found in tribal hill area of Bangladesh. This plant is used as folklore medicine in Chakma tribe. Two antiviral bioactive compounds have been isolated from ethanolic extract of the whole plant namely maltol b-D-apiofuranosyl-b-D-glucopyranoside, and grevilloside G.

These phytocompounds showed anti-RSV activity. Aegle marmelos L. Corrêa, a member of Rutaceae family, is a food producing plant which is found everywhere in Bangladesh. It is commonly known as bael or stone apple or wood apple. In Ayurveda, various parts of this plant are used because of having antidiarrhoeal, antimicrobial, antiviral, radioprotective, anticancer, chemopreventive, antipyretic, ulcer healing, antigenotoxic, diuretic, antifertility, and anti-inflammatory properties.

This plant produces a bioactive compound named seselin having activity against multiple targets of SARS-CoV In silico molecular docking study showed that seselin has inhibitory potential to the receptors SARS-CoV-2S protein binding energy: 6. A number of citrus fruits producing medicinal plants namely Citrus limon L.

Osbeck, Citrus sinensis L. Osbeck, and Citrus paradisi Macfad. are also found in this family which are commonly known as lemon, orange and grapefruit sequentially.

All of them are very rich sources of vitamin C which fastens healing of COVID by boosting immunity Bellavite and Donzelli, Essential oils extracted from the fruits of these medicinal plants have been reported for having inhibitory potential to HAV Battistini et al. Potent antiviral compounds named hesperidin and luteolin have been isolated from fruit of C.

An in silico study has demonstrated that hesperidin showed efficacy to inhibit spike protein and Mpro that modulate the immature proteins pp1a and ppa1b to the complex and functional one to progress replication process of SARS-CoV-2 Bellavite and Donzelli, Furthermore, luteolin has also been reported for having inhibitory activities against ACE2 receptor both of the subtypes AT1 and AT2 and RdRp enzyme by an in silico assay Goyal et al.

Camellia sinensis L. Kuntze belonging to the family Theaceae is known as tea or green tea which is considered as the most popular drink in worldwide. In Bangladesh, this plant is cultivated in two fairly divergent ecological zones such as Surma valley in greater Sylhet and Halda valley in Chittagong Mamun, The novel antiviral bioactive compounds namely epigallocatechingallate EGCG , epicatechin gallate ECG and epicatechin EC have been isolated from the leaves of this plant.

EGCG has been reported for surprising and divergent antiviral activities. It binds to virion surface proteins and blocks the attachment of HSV-I to heparan sulfate of host cells. It inhibits RNA and DNA synthesis as well as antigen expression in HBV.

It has broad-spectrum antiviral activities on HCV, IAV, murine cytomegalovirus mCMV , vesicular stomatitis virus VSV , and reovirus as well. Apart from these, EGCG showed potency to inhibit HIV reverse transcriptase by downregulation of the expression of the HIV p24 antigen.

Jassim, M. Intermittent fasting and hormonal balance Body toning diet plant and herb species that have Antiviral medicinal plants as novel Antivirap agents Ativiral been pants, with surprisingly little overlap. Antibiral wide variety Antivirak active phytochemicals, including the flavonoids, terpenoids, lignans, sulphides, polyphenolics, coumarins, saponins, furyl compounds, alkaloids, polyines, thiophenes, proteins and peptides have been identified. Some volatile essential oils of commonly used culinary herbs, spices and herbal teas have also exhibited a high level of antiviral activity. However, given the few classes of compounds investigated, most of the pharmacopoeia of compounds in medicinal plants with antiviral activity is still not known. Viral infections affect three to Antivirak million patients annually. While commonly used Hydrating beauty products often Body toning diet limited meidcinal and serious Antivral effects, herbal extracts have been Body toning diet medicjnal for medicinal purposes since Body toning diet times and are known for their antiviral properties and more tolerable side effects. Thus, naturally based pharmacotherapy may be a proper alternative for treating viral diseases. With that in mind, various pharmaceutical formulations and delivery systems including micelles, nanoparticles, nanosuspensions, solid dispersions, microspheres and crystals, self-nanoemulsifying and self-microemulsifying drug delivery systems SNEDDS and SMEDDS have been developed and used for antiviral delivery of natural products. These diverse technologies offer effective and reliable delivery of medicinal phytochemicals.