POTENTIAL PHYTOCONSTITUENTS FROM NATURAL PRODUCTS FOR COMBATING AGAINST CORONAVIRUS DISEASE-19 (SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS-2) - A REVIEW

Coronavirus called as coronavirus diseases (COVID)-19 (severe acute respiratory syndrome coronavirus [SARS-CoV]-2) is a viral infection which is spreading to a great extent and affecting many people worldwide, many developed and developing countries are severely affected by the virus. The World Health Organization (WHO) is taking serious preventive measures to stop this viral infection worldwide. The coronavirus is a big threat to human beings and controlling the emerging viral infections is a global concern. Antiviral drug such as Remdesivir has been approved by the FDA, but combating against these viral infections is a great challenge to scientists and researchers with the available few antiviral drugs due to severe side effects and toxicity. Many drugs such as hydroxy chloroquin, Remdesivir, and vaccines have been recommended for combating this virus. Few Polyherbal formulations and Ayurvedic formulations containing antiviral phytoconstituents have been recommended to boost the immunity. Some drugs and phytoconstituents are under different phases of human clinical trials. The currently available synthetic drugs and vaccines for the treatment of viral infections have severe side effects. Medicinal plants play a critical role in treating viral infections by developing immunity against viral diseases. Some medicinal plants which were used as antipyretic, analgesic, and anti-inflammatory activity helped in treating various diseases and viral infections. Many plants contain flavonoids such as quercetin, luteolin, apigenin, and polyphenols such as thymoquinone, phytosteroids such as cucurbitacin and others which may likely to act as antioxidants and immunomodulatory that can fight against COVID-19. The current review provides information on phytochemical constituents present in medicinal plants, their mechanism of action, in silico molecular docking studies and human clinical trials to treat viral disorders.


INTRODUCTION
Coronavirus called as coronavirus diseases (COVID)-19 pandemic a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a viral infection which is spreading to a great extent and many people are affected with the virus worldwide. The WHO has taken various preventive measures and recommended countries and advised people to wear masks, use sanitizers, wash hands regularly, maintaining social distance and also advised to boost their immunity by taking nutritious food and Immunomodulators. Hence, many developed and developing countries are affected with this virus. Scientists and researchers around the globe are inventing new drugs and identifying new phytochemical compounds to fight against viral infections. Since viral diseases are spreading to a large extent worldwide, stopping the spreading of infections is a global concern. Since people nowadays do not have natural immunity, so increasing immunity is also a global concern [1]. Coronavirus a deadly virus killing many people in the world, this virus is an air borne virus which spreads in air either by coughing and sneezing and easily invades the lungs through nose or mouth. The virus invades the respiratory tract and creates difficulty in breathing. The virus takes a week and then invades the lower respiratory tract and slowly creates difficulty in breathing. The patient must be isolated for 2-3 weeks to avoid spreading of the virus to other people; it may take around 4 weeks for complete recovery from the viral infection [2]. People affected with Coronavirus can experience a mildto-moderate symptoms such as respiratory illness and recover without requiring hospitalization for treatment. However, this is not in the case with older people with chronic illness such as chronic respiratory illness, cardiovascular problem, diabetes, and cancer may experience serious symptoms. The symptoms for Coronavirus include fever, dry cough, tiredness, body pains, throat infection, diarrhea, conjunctivitis, headache, loss of taste or smell, skin rashes, and discoloration of fingers and toes. Difficulty in breathing, chest pain and loss of speech are the serious and severe symptoms. The virus can spread by coughing and sneezing, the spreading can be prevented by covering the nose and mouth [3]. Remdesivir is a prodrug a ribonucleotide analogue inhibitor of viral RNA polymerase. Remdesivir was approved by the FDA for the treatment of COVID-19 which has been recommended by the WHO. Remdesivir was developed for the treatment of hepatitis C, Ebola virus disease, and other viral infections. It has also been investigated for its in vitro activity against SARS-CoV-2. Remdesivir decreased the virus levels in the lungs and exhibited less lung damage in patients with COVID-19 [4].

STRUCTURE AND FUNCTIONS OF LUNGS
The lungs are present in the thoracic cavity, which is enclosed by the rib cage. The ribcage protects the lungs from injury. The diaphragm is a skeletal muscle sheet that runs from the base of the lungs to the top of the lungs. The diaphragm separates the stomach and intestines from the lungs. The diaphragm is controlled by the sympathetic nervous system, and its primary function is respiration. The upper and lower respiratory tracts make up the respiratory tract. The nose and nasal passages, as well as the pharynx and larynx, which are located above the vocal cords, make up the upper respiratory tract. The larynx, which is located below the vocal cords, as well as the trachea, bronchi, and bronchioles, make up the lower respiratory tract. The lungs, which are found in the lower respiratory tract, contain the respiratory bronchioles, alveolar ducts, alveolar sacs, and alveoli. The nasal cavity is where air initially enters the nose; the inner layer of the nose is made up of a layer of nasal mucosa that functions as a filter, preventing hazardous substances, and pollutants from entering. The air passes through the pharynx, which connects the esophagus and the larynx. The epiglottis is a unique layer of cartilage that covers the larynx. The epiglottis opens to allow air into the alveoli but shuts to keep food out of the airway. The air enters the larynx and travels to the trachea, where it splits into the right and left main bronchi. The bronchi are made up of smaller structures called bronchioles that eventually join with specialized microscopic structures. Each bronchi split into a secondary bronchus that rises into tertiary bronchi called alveoli; the main function of alveoli is gaseous exchange [5].

STEAM THERAPY FOR COVID-19
Steam therapy is a best alternative method to overcome the symptoms of COVID-19, steam therapy with volatile oil containing plants, cinnamon bark, Cinnamon zeylanicum, clove, Eugenia caryophyllus, garlic, Allium sativum, black pepper, Piper nigrum, Piper betle, ginger, Zingiber officinale, etc. Steam inhalation is the most extensively used homemade remedy in the nasal passages to get relief from respiratory infections such as common cold and sinus problems. In this method, water vapor from warm water passes into the mucus membrane into the nasal passages, throats, and lungs. The water vapor from steam can get rid of symptoms such as alleviate irritation in the mucous membrane, inflammation, swollen blood vessels, relaxation of throat muscles, soreness and inflammation and dilates blood vessels improving blood circulation congestion, and other respiratory symptoms. Steam therapy can be recommended for a blocked nose, inflammation in the blood vessels and acute upper respiratory infection such as a cold or sinus infection [6].
Many medicinal plants contain flavonoids such as quercetin, luteolin, apigenin, and polyphenols such as thymoquinone, phytosteroids such as cucurbitacin and others which may likely to act exhibiting antioxidant and immunomodulatory activity that can quell the cytokine storm in COVID-19. Virus replication is inhibited by zinc as zinc inhibits viral Rdrp enzyme. Zinc is to be taken into cell by zinc ionophore compounds such as quercetin (naturally present in red onion, guava leaves and fruit, blue berries, and grape seeds) and thymoquinone. As plants contain quercetin and thymoquinone, they take zinc into cell and inhibit viral Rdrp; hence, there is possibility of stopping viral replication of SARS-COV-2 virus. Cytokine storm can be stopped by either flavonoids such as quercetin or phytosterols present in plants.

THE ROLE OF HERBAL MEDICINE
The Indian system of medicine or alternative system of medicine which include Ayurveda, Siddha, Unani, and Homeopathy are effective against many diseases, including viral infections and cancer but potency, quality, and safety needs to be enhanced in certain stages of production. The associated adverse effects and side effects need to be reduced. A number of new herbal products are introduced in the global market every year. About 80% of the people in developed and developing countries in many parts of the world still rely on traditional herbal medicine and their products for their primary healthcare and living [7]. Phytoconstituents present in natural products have been used for the treatment of many chronic disease conditions [8,9]. Many drugs and phytoconstituents are obtained from plant-derived compounds [10]. Therapeutic efficacy needs to be improved at every stage of preparation to ensure the quality, safety, and potency without side effects and toxic effects. Hence, standardization protocols need to be improved to ensure the quality of products. Standardized herbal products of reliable quality and welldefined phytoconstituents are required for pre-clinical and clinical trials to produce beneficial therapeutic efficacy. Phytochemical compounds play a crucial role in the field of drug discovery and development of antiviral agents with significant pharmacological action [11,12]. Many anti-infective and anticancer drugs are derived from plant derived compounds [13]. Herbal practitioners used herbal medicine since ancient times to cure several human aliments [14]. Herbal remedies are used to treat innumerable inflictions and diseases [15]. Many phytochemical compounds obtained from herbs have been reported to have strong antiviral activity against many viral infections. These phytoconstituents must be subjected to preclinical studies and human clinical trials to determine their effectiveness and toxicity studies. Fig. 1 Represents the phytoconstituents from natural products.

EXTRACTION OF PHYTOCONSTITUENTS FROM NATURAL PRODUCTS
Extraction of phytoconstituents from medicinal plants and natural products can be extracted by maceration and hot continuous percolation or Soxhlet extraction method. The powdered plant material is extracted with solvents such as non-polar solvents, mid polar solvents, and polar solvents. Non-polar solvents include petroleum ether or benzene or hexane mainly to remove the fat soluble constituents such as fixed oils, fats, and waxes. Then extracted with solvents such as chloroform, to separate alkaloids and other secondary metabolites and mid polar solvents or lower alcohols ethanol and methanol to separate glycosides and tannins and then finally extracted with water to remove water soluble constituents. The extract obtained after extraction is subjected to evaporation/concentration using a rotary evaporator. The extract can be further subjected to isolation of phytoconstituents by column chromatography. The extract can be used for identification of active constituents by preliminary phytochemical analysis by subjecting to various chemical tests to identify alkaloids, carbohydrates, glycosides, terpenoids, tannins, flavonoids, phytosterols, phenolic compounds, steroids, etc. The concentrated product can be stored or preserved in a desiccator or refrigerator. The isolated compound can be further subjected for chromatography by thin-layer chromatography, highperformance thin-layer chromatography (HPTLC), high-performance liquid chromatography (HPLC), etc., the compound can be characterized by spectroscopic methods which include ultraviolet-Visible spectroscopy, infrared spectroscopy, NMR spectroscopy, and MASS spectroscopy methods. The characterized compound can be used for pharmacological screening by in vitro and in vivo methods using animals for preclinical evaluation and human clinical trials. The efficacy and potency of the drugs can be evaluated to know the toxicity and side effects of the compounds. The toxicity of the compound can be tested according to OECG guidelines [16]. Table 1 specifies potent active constituents against COVID-19. Fig. 2 represents the Extraction of Phytoconstituents from Medicinal Plants.

Anti-viral activity of Z. officinale
Anti-viral activity of Z. officinale Ginger ingredients against the Chikungunya virus was investigated [32]. Fresh ginger Z. officinale has anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines [33]. Molecular docking studies of the phytocompounds of C. medica and Z. officinale were studied to find out whether these compounds could inhibit the receptor binding of SARS-CoV-2 spike protein (S protein) as well as the angiotensinconverting enzyme 2 (ACE-2), as evidenced from their docking into binding/active sites [34]. Molecular docking studies were performed on 27 phytocompounds derived from P. nigrum, Syzygium aromaticum, and Z. officinale roscoe was studied against protease of COVID-19. Out of 27 selected phytocompounds guaiol and gingeronone A has displayed significant inhibitory potential against coronavirus's selected targets [35]. The two compounds Tellimagrandin-II from S. aromaticum L. and O-Demethyl-demethoxy-curcumin from Curcuma longa L. were found to be highly potential due to their higher binding affinity and significant binding free energy (MM-PBSA), along with favorable ADMET properties and stable intermolecular interactions with hotspots (including the ASN343 glycosylation site) [36].

Anti-viral activity of Andrographis paniculata
A. paniculata extract and its major component andrographolide were optimized with a high-content imaging platform and the plaque Chandrasekar et al. T. cordifolia: Tinospora cordifolia assay for viral output study using the legitimate model of human lung epithelial cells, Calu-3, to determine anti-SARS-CoV-2 activity [37]. Andrographolide from A. paniculata as a potential inhibitor of the main protease of SARS-COV-2 (Mpro) through in silico studies such as molecular docking, target analysis, toxicity prediction, and ADME prediction were evaluated [38].

Anti-viral activity of Justicia adhatoda
Synergistic antiviral effects against SARS-CoV-2 by plant-based molecules were investigated [40]. The alkaloids from leaf extracts of J. adhatoda have also been reported to possess anti-viral activity [41]. Three compounds such as anisotine and vasicoline of J. adhatoda and Pemirolast are very good inhibitors and effective against protease inhibitor and replicase inhibitor of COVID-19 virus using COVID-19 Docking Server [42]. The acetone and methanol extracts of Moringa oleifera, Adhatoda vasica, and Cassia fistula were tested against sputum samples of 120 patients suffering from respiratory tract infection (RTI), tuberculosis infection, and multidrug resistant (MDR) isolates. MDR strains, showed remarkable sensitivity against all the three plants [43].
The study revealed that Plectranthus amboinicus as the inhibitor of novel coronavirus (COVID-19) targets, that is, 3CLpro, PLpro, and spike protein, through in silico molecular docking and other computational approaches against COVID-19 [44].
Saussurea costus has immunomodulatory effects on cytokine release and has complement-inhibitor substances helpful in the treatment of some diseases related to marked activation of the complement system, like respiratory distress [45].

Anti-viral activity of Tinospora cordifolia
Based on the therapeutic significance, the chemical constituents from the extract of T. cordifolia belonging to various classes such as alkaloids, lignans, steroids, and terpenoids are investigated as potential drug candidates for COVID-19 [46]. In silico molecular docking studies were performed on T. cordifolia containing five compounds such as berberine, β-sitosterol, coline, tetrahydropalmatine, and octacosanol, 3CL pro is used to study drug:3CL pro interactions and thus to investigated to be used as an anti-viral drug against SARS-CoV-2 [47]. Molecular docking study showed six probable inhibitors against SARS-CoV-2 M pro (Main protease), two from Withania somnifera (Ashwagandha) Withanoside V and Somniferine, one from T. cordifolia (Giloy) (Tinocordiside), and three from Ocimum sanctum (Tulsi) (Vicenin, Isorientin 4′-O-glucoside 2″-O-p-hydroxybenzoagte and Ursolic acid) [48]. In silico molecular docking approach has been carried out to dock the ligands (various secondary metabolites from T. cordifolia) to the target (SARS-CoV-2 main protease) and compared its efficacy against standard drugs (Azithromycin, Chloroquine, Hydroxychloroquine, Favipiravir, and Remdesivir). Columbin, Tinosporide, N-trans-feruloyl-tyraminediacetate, Amritoside C, Amritoside B, Amritoside A, Tinocordifolin, Palmatoside G, Palmatoside F, and Maslinic acids are other molecules considered to be the key molecules based on their docking score [49]. The aqueous extracts of T. cordifolia (willd.) Hook. f. and Thomson in the form of Giloy Ghanvati, as a means of treatment to the SARS-CoV-2 spike-protein induced disease phenotype in a humanized zebrafish model were evaluated [50].
The molecular docking studies of 200 ligands were studied out of them best ten were selected based on drug discovery parameters such as S-score, ligand interactions, hydrophobic interactions, and drug likeness. The ten best selected ligands were found to be verbenalin, epigallocatechin, swertisin, nobiletin, pinoresinol, caftaric acid, hesperetin, islandicin, neochlorogenic acid, and sesamin that exploit the potency as antagonists of viral protein. Among binding interactions of all ligands, Arg339 centered as the main interacting residue among almost all the ligands [52].
A molecular docking analysis was carried out using 171 essential oil components with SARS-CoV-2 main protease. The compound with the best normalized docking score to SARS-CoV-2 M pro was the sesquiterpene hydrocarbon (E)-β-farnesene. Essential oils may potentiate other antiviral agents, or they may provide some relief of COVID-19 symptoms [53]. The structures of bioactive phytoconstituents are depicted in Fig. 3.

Antiviral activity of two important Siddha Polyherbal formulations Kaba Sura Kudineer and Nilaveembu Kudineer (NVK)
The efficacy of NVK as an antiviral formulation against CHIKV and DENV was undertaken. This study provides insights to the possible mode of action of NVK in in vitro condition during CHIKV and DENV infection [57]. The phytoconstituents present in medicinal plants with therapeutic uses and pharmacological activity are represented in Table 2. The chemical structures of active phytoconstituents are depicted in Fig. 4.
The effectiveness of the KSK and NVK along with standard Allopathy Treatment was determined to compared with Placebo (Decaffeinated Tea) with standard Allopathy Treatment in the management of Symptomatic COVID-19 patients and also in reduction of Hospital Stay Time and Changes in Immunological (IL6) and Bio Chemical Markers (Ferritin, CRP, D-Dimer and LDH) [58].
The interaction of 47 active components identified from the ten different medicinal plants was investigated against the structural targets of SARS-CoV-2 (Mpro and spike protein) and human ACE2 receptor was explored through molecular docking analysis. The bioactive ligands such as Cucurbitacin E, Orientin, Bis-andrographolide, Cucurbitacin B, Isocucurbitacin B, Vitexin, Berberine, Bryonolic acid, Piperine, and Magnoflorine targeted the hotspot residues of SARS-CoV-2 main protease. The study emphasized that Cucurbitacin E and orientin could serve as a promising scaffold for developing anti-COVID-19 drug [59].
The in silico computational studies of phytoconstituents of Siddha official formulation Kabasura Kudineer and novel herbal preparation -JACOM could be affective against the ongoing pandemic novel coronavirus disease SARS-CoV-2. Totally, 37 compounds were screened, of these nine compounds showed high binding affinity against SARS-CoV-2 spike protein. Based on these, the new formulation called as "SNACK-V" was proposed. Based on further experiments and clinical trials, these formulations could be used for effective treatment of COVID-19 [60].  Table 3 The chemical structures of phytoconstituents are depicted in Fig. 5.
Agele marmelos bael fruit ethanolic extract have shown antiviral activity against Ranikhet disease virus. Marmilide is the most effective viricidal agent interfering with early events of replicating cycle. Thus, bael fruit has better viricidal potential and may be exploited as a potent antiviral agent in near future [80].
E. jambolana cold and hot aqueous extracts of bark and hot aqueous extract of leaves showed significant virucidal activity against H5N1 virus (100% inhibition) which was further confirmed in virus yield reduction assay (−98-99% reduction) and by egg based in vivo assay [81].

Vetiveria Zizanioides
Poaceae α-vetivone α-Vetivone is an organic compound that is classified as a sesquiterpene. It is a major component of the oil of vetiver, which is used to prepare certain high value perfumes [54]

Santalum Album
Santalaceae Santalol White sandalwood is used for treating the common cold, cough, bronchitis, fever, and sore mouth and throat. It is also used to treat urinary tract infections, liver disease, gallbladder problems, heatstroke, gonorrhea, headache, and conditions of the heart and blood vessels [

Antiviral activity of Azardirachta indica
Molecular docking studies identified three potential compounds from leaf extracts of neem (Nimbaflavone, Rutin, and Hyperoside) against Influenza virus strains having perfect binding with reported conserved residues (ASP302, SER50) of influenza virus nucleoprotein that is involved in the binding of drugs. Hyperoside from neem leaf extract along with drugs LGH, Naproxen, BMS-885838, and BMS-883559 showed best interactions with conserved residues of nucleoprotein [82]. The aqueous extract preparation from the barks of neem plant A. indica acts as a potent entry inhibitor against herpes simplex virus type-1 (HSV-1) infection into natural target cells [83]. Antibacterial as well as antiherpes virus activity of sulfonoquinovosyldiacylglyceride, a glycolipid, isolated from the leaves of A. indica has been described [84]. A total of 70 compounds from (A. indica or Neem) were virtually screened against these two proteins and further analyzed with molecular dynamics simulations, which resulted in the identification of a few common compounds with strong binding to both structural proteins. The compounds bind to biologically critical regions of M and E, indicating their potential to inhibit the functionality of these components. The computational approach may result in the identification of effective inhibitors of SARS-CoV-2 assembly [85]. The inhibitory activity of Neem extracts on Papain like protease (PLpro) of the novel coronavirus SARS-CoV-2 was examined. Desacetylgedunin (DCG) found in Neem seed showed the highest binding affinity toward PLpro. The significant effect of DCG on PLpro may help in therapeutic efforts against SARS-CoV-2 [86].
The possible effects of Nigella sativa were determine on immuneresponse and pathogenesis of H9N2 avian influenza virus in turkeys [87].

Antiviral activity of C. longa
The antiviral activity of curcumin and its new derivatives such as gallium-curcumin and Cu-curcumin on replication of HSV-1 in cell culture was designed. The study was performed as an in vitro study in which the antiviral activity of different concentrations of three substances including curcumin, Gallium-curcumin, and Cu-curcumin was tested on HSV-1. The cytotoxicity of the tested compounds was also evaluated on the Vero cell line. Curcumin and its new derivatives have remarkable antiviral effects on HSV-1 in cell culture [88]. The antiviral activity of C. longa Linn (CLL) against HBV replication in liver cells was investigated. Aqueous extract of CLL was prepared and used to analyze its antiviral activity against HBV replication in HepG 2.2.15 cells, which contain HBV genomes. CLL extract can be used as a safe and specific drug for patients with liver diseases caused by HBV infection [89].

Antiviral activity of Piper longum and P. nigrum
The ethanolic extract of P. longum Linn was screened against in vitro anti-HBV activity by using Hep G 2.2.15 cell line. The compound piperine (7) possessed remarkable inhibitory HBV activity, against the secretion of hepatitis B virus surface antigen and hepatitis B virus e antigen with the Selectivity Index values of 15.7 and 16.8, respectively [90]. Ten piperamides from P. nigrum were isolated from a combined methanol/ dichloromethane extract (PNE) of black pepper fruits, and investigated for (1) their antiviral properties against three viruses related to the upper RTIs, and (2) their anti-proliferative activity in vascular smooth muscle cells, which is a key element in the prevention of restenosis. The extract of P. nigrum was found to inhibit coxsackie virus type B3 [91].  (5)) [92].

Antiviral activity of Phyllanthus niruri
The antiviral activity of the aqueous extract of four Phyllanthus species was evaluated against HSV-1 and HSV-2 in Vero cells by quantitative PCR [93]. P. niruri ethanol extract was evaluated for its anti-HCV activities. Anti-HCV activity was determined by in vitro culture cells of Huh 7it. Docking analysis was performed to predict the interaction phyllanthin and hypophyllantin, known compounds of P. niruri against HCV receptor. The ethanol extract of P. niruri may be good candidates for the development of anti-HCV drugs [94]. In vitro antiviral activity against HSV-1 was evaluated, 28 extracts corresponding to 24 plant species and 4 alga species were assayed. Six of the methanolic extracts inactivated viral particles by direct interaction and 14 presented antiviral activity when incubated with cells already infected. Most interesting antiviral   [95]. Four species of Phyllanthus were evaluated against anti-dengue agent (P. amarus, P. niruri, P. urinaria, and P. watsonii) and their polyphenolic compounds were identified through HPLC and LC-MS/MS analysis. MTS assay was then carried out to determine the maximal non-toxic dose of the extracts, followed by screening of the in vitro antiviral activity of aqueous cocktail extracts against DENV2 by means of time-of-addition (pre-, simultaneous, and post-) using RT-qPCR. Several active compounds including gallic acid, geraniin, syringin, and corilagen were identified. Phyllanthus showed strongest inhibitory activity against DENV2 with more than 90% of virus reduction in simultaneous treatment [96].
The anti-hepatitis C virus activity was evaluated in the Eclipta alba extract, bioassay based fractionation and identify anti-HCV phytochemicals from the active fractions were performed. Eclipta alba extract strongly inhibited RNA dependent RNA polymerase (RdRp) activity of HCV replicase in vitro. The identified compounds were wedelolactone, luteolin, and apigenin Bioassay-based fractionations [97].
Antioxidative, cytoprotective properties, and anti-HSV-1 activity were studied, antiviral activity was studied in Vero cells. Results highlighted different compositions of the extracts, with chlorogenic acid and delphinidin-3-rutinoside as the major constituents [98].

CONCLUSION AND FUTURE PERSPECTIVES
Preclinical studies in laboratory animal models and clinical studies are needed to prove the efficacy of these phytocompounds in inhibiting coronavirus. Conducting human clinical trials and observing the efficacy to reduce the multiplication of the virus. The introduction of plant products should be incorporated in food as nutraceuticals, because these are preparations from natural products, obtained from plants can act as immunomodulators. It is also necessary to conduct preclinical studies in vitro and in vivo on animals and clinical trials on patients to confirm their effectiveness in inhibiting COVID-19. The development of phytopharmaceuticals as an alternative approach could be seen as a potential treatment option against SARS-CoV-2 in current COVID-19 pandemic. Scarcity of the drugs and specific treatments for COVID-19 till date motivate the researchers to search for new alternatives for successfully combating the virus. The low toxicity and decreased side effects of herbal medicines and an easy development process provide additional advantages in their fast and wide usage. This review presents the essential information of plant extracts and phytoconstituents in the development of formulations with phytochemical compounds obtained from medicinal plants. Further investigation for future studies is recommended on naturally derived plant products alone or in integration with western medicine. However, further in vivo and in vitro studies need to be done to confirm the bioactivity of these compounds against COVID-19. The article was compiled from various literatures and it was an easy access to collect information from most of the articles published on COVID-19, since many articles were from open access journals.

ACKNOWLEDGMENTS
Declared none.

AUTHOR CONTRIBUTION
All the authors have equally contributed to the article.