Artemisia annua, amodiaquine, artemisinin for COVID-19

As the world desperately searches for ways to treat the coronavirus disease 2019 (COVID-19) pandemic, a growing number of people are turning to herbal remedies. The Artemisia species, such as A. annua and A. afra, in particular, exhibit positive effects against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and COVID-19 related symptoms. A. annua is a source of artemisinin, which is active against malaria, and also exhibits potential for other diseases. This has increased interest in artemisinin’s potential for drug repurposing. Artemisinin-based combination therapies, so-called ACTs, have already been recognized as first-line treatments against malaria. Artemisia extract, as well as ACTs, have demonstrated inhibition of SARS-CoV-2. Artemisinin and its derivatives have also shown anti-inflammatory effects, including inhibition of interleukin-6 (IL-6) that plays a key role in the development of severe COVID-19. There is now sufficient evidence in the literature to suggest the effectiveness of Artemisia, its constituents and/or artemisinin derivatives, to fight against the SARS-CoV-2 infection by inhibiting its invasion, and replication, as well as reducing oxidative stress and inflammation, and mitigating lung damage.

Fighting against the emergent coronavirus disease (COVID-19) remains a big challenge at the front of the world communities. Recent research has outlined the potential of various medicinal herbs to counteract the infection. This study aimed to evaluate the interaction of artemisinin, a sesquiterpene lactone extracted from the Artemisia genus, and its derivatives with the SARS-CoV-2 main protease. To assess their potential use against COVID-19, the interactions of the main active principle of Artemisia with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) was investigated through in silico probing. Our results showed that artemesinin and its derivatives manifested good oral absorption and bioavailability scores (0.55). They potently bound to the Mpro site of action—specifically, to its Cys145 residue. The selected compounds established two to three conventional hydrogen bonds with binding affinities ranging between −5.2 and −8.1 kcal/mol. Furthermore, artemisinin interactions with angiotensin converting enzyme 2 (ACE2) were dependent on the ACE2 allelic variants. The best score was recorded with rs961360700. A molecular dynamic simulation showed sufficient stability of the artemisinin–Mpro complex on the trajectory of 100 ns simulation frame. These binding interactions, together with drug-likeness and pharmacokinetic findings, confirmed that artemisinin might inhibit Mpro activity and explain the ethnopharmacological use of the herb and its possible antiviral activity against SARS-CoV-2 infection inducing COVID-19. Nevertheless, it interacted differently with the various ACE2 allelic variants reported to bind with the SARS-CoV-2 spike protein.

Abstract Background Novel Corona Virus Disease 2019 (COVID-19) is closely associated with cytokines storms. The Chinese medicinal herb Artemisia annua L. (A. annua) has been traditionally used to control many inflammatory diseases, such as malaria and rheumatoid arthritis. We performed network analysis and employed molecular docking and network analysis to elucidate active components or targets and the underlying mechanisms of A. annua for the treatment of COVID-19. Methods Active components of A. annua were identified through the TCMSP database according to their oral bioavailability (OB) and drug-likeness (DL). Moreover, target genes associated with COVID-19 were mined from GeneCards, OMIM, and TTD. A compound-target (C-T) network was constructed to predict the relationship of active components with the targets. A Compound-disease-target (C-D-T) network has been built to reveal the direct therapeutic target for COVID-19. Molecular docking, molecular dynamics simulation studies (MD), and MM-GBSA binding free energy calculations were used to the closest molecules and targets between A. annua and COVID-19. Results In our network, GO, and KEGG analysis indicated that A. annua acted in response to COVID-19 by regulating inflammatory response, proliferation, differentiation, and apoptosis. The molecular docking results manifested excellent results to verify the binding capacity between the hub components and hub targets in COVID-19. MD and MM-GBSA data showed quercetin to be the more effective candidate against the virus by target MAPK1, and kaempferol to be the other more effective candidate against the virus by target TP53. We identified A. annua’s potentially active compounds and targets associated with them that act against COVID-19. Conclusions These findings suggest that A. annua may prevent and inhibit the inflammatory processes related to COVID-19.

COVID-19 is rapidly spreading and there are currently no specific clinical treatments available. The absence of an immediate available vaccine against SARS-CoV-2 made it hard for health professionals to tackle the problem. Thus, the need of ready to use prescription drugs or herbal remedies is urgent. SARS-CoV-2 main protease (Mpro) and Angiotensin Converting Enzyme2 (ACE2) protein structure are made available to facilitate finding solutions to the present problem. In this brief research, we compare the efficacy of some natural compounds against COVID-19 Mpro and ACE2 to that of Hydroxy-Chloroquine in silico.Molecular docking investigations were carried out using AutoDock. Virtual screening was performed using AutoDock Vina and the best ligand / protein mode was identified based on the binding energy. Amino Acids residues of ligands interactions were identified using PyMOL. According to present research results, Quercetin, Hispidulin, Cirsimaritin, Sulfasalazine, Artemisin and Curcumin exhibited better potential inhibition than Hydroxy-Chloroquine against COVID-19 main protease active site and ACE2. Our provided docking data of these compounds may help pave a way for further advanced research to the synthesis of novel drug candidate for COVID-19.

ABSTRACTOur COVID-19 drug candidate ARTIVeda™/PulmoHeal is a novel gelatin capsule formulation of the Artemisia extract Ayurveda for oral delivery of TGF-β targeting anti-malaria phytomedicine Artemisinin with documented anti-inflammatory and anti-SARS-CoV-2 activity. Here we report the safety and efficacy of ARTIVeda™ in adult COVID-19 patients with symptomatic mild-moderate COVID-19, who were treated in a randomized, open-label Phase IV study in Bangalore, Karnataka, India (Clinical Trials Registry India identifier: CTRI/2020/09/028044). ARTIVeda showed a very favorable safety profile, and the only ARTIVeda-related adverse events were transient mild rash and mild hypertension. Notably, ARTIVeda, when added to the SOC, accelerated the recovery of patients with mild-moderate COVID-19. While all patients were symptomatic at baseline (WHO score = 2-4), 31 of 39 (79.5%) of patients treated with ARTIVeda plus SOC became asymptomatic (WHO score = 1) by the end of the 5-day therapy, including 10 of 10 patients with severe dry cough 7 of 7 patients with severe fever. By comparison, 12 of 21 control patients (57.1%) treated with SOC alone became asymptomatic on day 5 (P=0.028, Fisher’s exact test). This clinical benefit was particularly evident when the treatment outcomes of hospitalized COVID-19 patients (WHO score = 4) treated with SOC alone versus SOC plus ARTIVeda were compared. The median time to becoming asymptomatic was only 5 days for the SOC plus ARTIVeda group (N=18) but 14 days for the SOC alone group (N=10) (P=0.004, Log-rank test). These data provide clinical proof of concept that targeting the TGF-β pathway with ARTIVeda may contribute to a faster recovery of patients with mild-moderate COVID-19 when administered early in the course of their disease.

AbstractEthnopharmacological relevanceFor millennia in Southeast Asia,Artemisia annuaL. was used to treat “fever”. This medicinal plant is effective against numerous infectious microbial and viral diseases and is used by many global communities as a source of artemisinin derivatives that are first-line drugs to treat malaria.Aim of the StudyThe SARS-CoV-2 (Covid-19) global pandemic has killed millions and evolved numerous variants, with delta being the most transmissible to date and causing break-through infections of vaccinated individuals. We further queried the efficacy ofA. annuacultivars against new variants.Materials and MethodsUsing Vero E6 cells, we measured anti-SARS-CoV-2 activity of dried-leaf hot-waterA. annuaextracts of four cultivars, A3, BUR, MED, and SAM, to determine their efficacy against five fully infectious variants of the virus: alpha (B.1.1.7), beta (B.1.351), gamma (P.1), delta (B.1.617.2), and kappa (B.1.617.1).ResultsIn addition to being effective against the original wild type WA1,A. annuacultivars A3, BUR, MED and SAM were also potent against all five variants. IC50and IC90values based on measured artemisinin content ranged from 0.3-8.4 μM and 1.4-25.0 μM, respectively. The IC50and IC90values based on dried leaf weight (DW) used to make the tea infusions ranged from 11.0-67.7 μg DW and 59.5-160.6 μg DW, respectively. Cell toxicity was insignificant at a leaf dry weight of ≤50 μg in the extract of any cultivar.ConclusionsResults suggest that oral consumption ofA. annuahot-water extracts (tea infusions), could provide a cost-effective therapy to help stave off the rapid global spread of these variants, buying time for broader implementation of vaccines.

The rising threat of pandemic viruses, such as SARS-CoV-2, requires development of new preclinical discovery platforms that can more rapidly identify therapeutics that are activein vitroand also translatein vivo. Here we show that human organ-on-a-chip (Organ Chip) microfluidic culture devices lined by highly differentiated human primary lung airway epithelium and endothelium can be used to model virus entry, replication, strain-dependent virulence, host cytokine production, and recruitment of circulating immune cells in response to infection by respiratory viruses with great pandemic potential. We provide a first demonstration of drug repurposing by using oseltamivir in influenza A virus-infected organ chip cultures and show that co-administration of the approved anticoagulant drug, nafamostat, can double oseltamivir’s therapeutic time window. With the emergence of the COVID-19 pandemic, the Airway Chips were used to assess the inhibitory activities of approved drugs that showed inhibition in traditional cell culture assays only to find that most failed when tested in the Organ Chip platform. When administered in human Airway Chips under flow at a clinically relevant dose, one drug – amodiaquine - significantly inhibited infection by a pseudotyped SARS-CoV-2 virus. Proof of concept was provided by showing that amodiaquine and its active metabolite (desethylamodiaquine) also significantly reduce viral load in both direct infection and animal-to-animal transmission models of native SARS-CoV-2 infection in hamsters. These data highlight the value of Organ Chip technology as a more stringent and physiologically relevant platform for drug repurposing, and suggest that amodiaquine should be considered for future clinical testing.

Coronavirus disease (COVID-19) is still a severe concern, especially in Africa with suboptimal intention rates of vaccination. This flagged the requirement of plant-based remedies as an alternative treatment. In this study we integrated metabolomics and chemometrics approaches with In silico and In vitro approaches to accelerate and unravel compounds from commonly used South African plants that may inhibit SARS-CoV-2 main protease. The selected commonly used plants, Artemisia afra and Artemisia annua, were found to be non-toxic against Vero cells, as determined by the resazurin cell viability assay. Metabolites profiling revealed eighty-one compounds and the top three hit compounds, quercetin 3-O-(6“-acetyl-glucoside), 2”-O-acetylrutin, and quercetin 3-(6”-malonyl-glucoside), had binding affinities of -9.3 kcal/mol, -9.5 kcal/mol, and -9.3 kcal/mol, respectively. The 2”-O-acetyl group of the rutin moiety and quercetin moiety produces a hydrogen bond with the amide nitrogen of His41 and with the side chain carboxylate of Cys145, respectively. Molecular dynamics simulations revealed a stable binding of the docked complexes. In silico observations were validated by In vitro bioassay, which flagged the ability of these compounds to inhibit SARS-CoV-2 3CLpro. The collected analysed data of this study does not only draw special attention to the surfaced 2”-O-acetylrutin as the best suitable inhibitor of SARS-CoV-2 3CLpro, but also indirectly reveals the importance of integrating metabolomics and chemometrics approaches with In silico and In vitro approaches to accelerate and unravel compounds from South African commonly used plants.

There is currently no particular cure for coronavirus disease-19 (COVID-19). However, studies suggest that certain medicinal plants, fruits, and vegetables possess bioactive substances capable of ameliorating the disease. This review aims to articulate fruits, vegetables, and medicinal plants that have anti-coronavirus properties. Relevant articles were collected from reputable academic repositories, namely SpringerLink, PubMed, Google Scholar, and Scopus. Available information shows that alkaline-rich fruits and vegetables, such as mango, cabbage, lemon, onion, okra, carrot, cucumber, pepper, spinach, and avocado, have anti-coronavirus properties. The mentioned fruits and vegetables stimulate an unfavorable pH for the replication of the virus and normalize the acid-base imbalance induced in the lungs and kidneys of the infected. Fruits and vegetables also contain health-boosting substances such as proteins, amino acids, glycosides, vitamins, and minerals. Medicinal plants, including Clitoria ternatea L., Vitex trifolia L., Sphaeranthus indicus L., Clerodendrum inerme L. Gaertn., Glycyrrhiza glabra L., Strobilanthes cusia (Nees) Kuntze, Vitis vinifera var. aestivalis (Michx.) Kuntze, Hyoscyamus niger L., and Cedrela Sinensis Juss., also possess anti-coronavirus properties. Clitoria ternatea and Cedrela sinensis reduce the virus’s replication by shredding its receptor, called the angiotensin-converting enzyme 2 (ACE2). Vitex trifolia and Sphaeranthus indicus prevent hyper-inflammatory responses and cytokine storms. Glycyrrhiza glabra induces nitrous oxide synthase and blocks the virus’s replication. Clerodendrum inerme and Strobilanthes cusia inhibit the virus’s ribosome and protein translation. Vitis vinifera represses nucleocapsid protein and lowers apoptosis. Hyoscyamus niger inhibits Ca2+ channels and lessens breathing difficulties induced by the coronavirus. Thus, dietary supplements and drugs formulated with these medicinal plants, fruits, and vegetables may lessen the effects of COVID-19.

Drug repurposing has emerged as a promising strategy in the rapid development of effective therapeutics for COVID-19. This approach leverages existing medications, previously approved for other indications, to target the pathophysiological mechanisms of SARS-CoV-2 infection. Several drugs were tested during the COVID-19 pandemic, developed originally for other purposes and under less-than-ideal conditions. Some of the most well-known include remdesivir, an Ebola drug approved by the FDA for emergency use to treat COVID-19, and dexamethasone, a corticosteroid that reduces death associated with severe infection through immunomodulation. However, while hydroxychloroquine and ivermectin, among others, showed very meager or no benefit, it is clear that such early promise must be subjected to firm testing. Despite such promises, drug repurposing may face several inconsistent clinical outcomes, questions over safety, and the inability to address all forms of COVID-19 pathology. Key candidates identified through high-throughput screening and computational methods include antiviral agents, anti-inflammatory drugs, and those targeting host cell pathways critical for viral replication. This review discusses the efficacy and mechanisms of these repurposed drugs, highlights ongoing clinical trials, and addresses challenges such as resistance and optimal dosing. Ultimately, drug repurposing represents a crucial component of the multi-faceted response required to combat the COVID-19 pandemic effectively.

The advantages of a treatment modality that combines two or more therapeutic agents with different mechanisms of action encourage the study of hybrid functional compounds for pharmacological applications. Molecular hybridization, resulting from a covalent combination of two or more pharmacophore units, has emerged as a promising approach to overcome several issues and has also been explored for the design of new drugs for COVID-19 treatment. In this review, we presented an overview of small-molecule hybrids from both natural products and synthetic sources reported in the literature to date with potential antiviral anti-SARS-CoV-2 activity.

Abstract The global efforts in the past year have led to the discovery of nearly 200 drug repurposing candidates for COVID-19. Gaining more insights into their mechanisms of action could facilitate a better understanding of infection and the development of therapeutics. Leveraging large-scale drug-induced gene expression profiles, we found 36% of the active compounds regulate genes related to cholesterol homeostasis and microtubule cytoskeleton organization. Following bioinformatics analyses revealed that the expression of these genes is associated with COVID-19 patient severity and has predictive power on anti-SARS-CoV-2 efficacy in vitro. Monensin, a top new compound that regulates these genes, was further confirmed as an inhibitor of SARS-CoV-2 replication in Vero-E6 cells. Interestingly, drugs co-targeting cholesterol homeostasis and microtubule cytoskeleton organization processes more likely present a synergistic effect with antivirals. Therefore, potential therapeutics could be centered around combinations of targeting these processes and viral proteins.

Background: Gabon faced COVID-19 with more than 49,000 individuals tested positive and 307 recorded fatalities since the first reported case in 2020. A popular hypothesis is that the low rate of cases and deaths in the country was attributed to the use of medicinal plants in prevention and treatment. This study aimed to document the plants used for remedial and preventive therapies by the Gabonese population during the COVID-19 pandemic and to pinpoint specific potential plant species that merit further investigation.Methods: An ethnobotanical survey involving 97 participants was conducted in Libreville. Traditional healers and medicinal plant vendors were interviewed orally using a semi-structured questionnaire sheet, while the general population responded to an online questionnaire format. Various quantitative indexes were calculated from the collected data and included the relative frequency of citation (RFC), use value (UV), informant consensus factor (ICF), relative importance (RI), and popular therapeutic use value (POPUT). One-way ANOVA and independent samples t-test were used for statistical analyses. p-values ≤0.05 were considered significant.Results: The survey identified 63 plant species belonging to 35 families. Prevalent symptoms treated included fever (18%), cough (16%), fatigue (13%), and cold (12%). The demographic data highlighted that 52.58% of male subjects (p > 0.94) aged 31–44 years were enrolled in the survey, of which 48.45% (p < 0.0001) and 74.73% (p < 0.99) of informants had university-level education. In addition, the results indicated that a total of 66% of the informants used medicinal plants for prophylaxis (34%), for both prevention and treatment (26%), exclusively for treatment (3%), and only for prevention (3%) while suffering from COVID-19, against 34% of the participants who did not use plants for prevention or treatment. Annickia chlorantha, Citrus sp., Alstonia congensis, Zingiber officinale, and Carica papaya emerged as the most commonly cited plants with the highest RFC (0.15–0.26), UV (0.47–0.75), and RI (35.72–45.46) values. Most of these plants were used either individually or in combination with others.Conclusion: The survey reinforces the use of traditional medicine as a method to alleviate COVID-19 symptoms, thereby advocating for the utilization of medicinal plants in managing coronavirus infections.

AbstractThe urgent need for safe, efficacious, and accessible drug treatments to treat coronavirus disease 2019 (COVID‐19) prompted a global effort to evaluate drug repurposing opportunities. Pyronaridine and amodiaquine are both components of approved antimalarials with in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). In vitro activity does not always translate to clinical efficacy across a therapeutic dose range. This study applied available, verified, physiologically based pharmacokinetic (PBPK) models for pyronaridine, amodiaquine, and its active metabolite N‐desethylamodiaquine (DEAQ) to predict drug concentrations in lung tissue relative to plasma or blood in the default healthy virtual population. Lung exposures were compared to published data across the reported range of in vitro EC50 values against SARS‐CoV‐2. In the multicompartment permeability‐limited PBPK model, the predicted total Cmax in lung mass for pyronaridine was 34.2 μM on Day 3, 30.5‐fold greater than in blood (1.12 μM) and for amodiaquine was 0.530 μM, 8.83‐fold greater than in plasma (0.060 μM). In the perfusion‐limited PBPK model, the DEAQ predicted total Cmax on Day 3 in lung mass (30.2 μM) was 21.4‐fold greater than for plasma (1.41 μM). Based on the available in vitro data, predicted drug concentrations in lung tissue for pyronaridine and DEAQ, but not amodiaquine, appeared sufficient to inhibit SARS‐CoV‐2 replication. Simulations indicated standard dosing regimens of pyronaridine‐artesunate and artesunate‐amodiaquine have potential to treat COVID‐19. These findings informed repurposing strategies to select the most relevant compounds for clinical investigation in COVID‐19. Clinical data for model verification may become available from ongoing clinical studies.

The expected progress in SARS-CoV-2 vaccinations, as anticipated in 2020 and 2021, has fallen short, exacerbating global disparities due to a lack of universally recognized “safe and effective” vaccines. This study focuses on extracts of South African medicinal plants, Artemisia annua and Artemisia afra, to identify metabolomic bioactive compounds inhibiting the binding of the SARS-CoV-2 spike protein to ACE2 receptors. The extracts were monitored for cytotoxicity using a resazurin cell viability assay and xCELLigence real-time cell analyzer. Chemical profiling was performed using UPLC-MS/MS, orthogonal projection to latent structures (OPLS), and evaluated using principle component analysis (PCA) models. Identified bioactive compounds were subjected to in vitro SARS-CoV-2 enzyme inhibition assay using standard methods and docked into the spike (S) glycoprotein of SARS-CoV-2 using Schrodinger® suite followed by molecular dynamics simulation studies. Cell viability assays revealed non-toxic effects of extracts on HEK293T cells at lower concentrations. Chemical profiling identified 81 bioactive compounds, with compounds like 6″-O-acetylglycitin, 25-hydroxyvitamin D3-26,23-lactone, and sesaminol glucoside showing promising binding affinity. Molecular dynamics simulations suggested less stable binding, but in vitro studies demonstrated the ability of these compounds to interfere with SARS-CoV-2 spike protein’s binding to the human ACE2 receptor. Sesaminol glucoside emerged as the most effective inhibitor against this interaction. This study emphasizes the importance of multiplatform metabolite profiling and chemometrics to understand plant extract composition. This finding is of immense significance in terms of unravelling metabolomics bioactive compounds inhibiting the binding of the SARS-CoV-2 spike protein to ACE2 receptors and holds promise for phytotherapeutics against SARS-CoV-2.

Abstract Background In November 2019, the world faced a pandemic called SARS-CoV-2, which became a major threat to humans and continues to be. To overcome this, many plants were explored to find a cure. Methods Therefore, this research was planned to screen out the active constituents from Artemisia annua that can work against the viral main protease Mpro as this non-structural protein is responsible for the cleavage of replicating enzymes of the virus. Twenty-five biocompounds belonging to different classes namely alpha-pinene, beta-pinene, carvone, myrtenol, quinic acid, caffeic acid, quercetin, rutin, apigenin, chrysoplenetin, arteannunin b, artemisinin, scopoletin, scoparone, artemisinic acid, deoxyartemisnin, artemetin, casticin, sitogluside, beta-sitosterol, dihydroartemisinin, scopolin, artemether, artemotil, artesunate were selected. Virtual screening of these ligands was carried out against drug target Mpro by CB dock. Results Quercetin, rutin, casticin, chrysoplenetin, apigenin, artemetin, artesunate, sopolin and sito-gluside were found as hit compounds. Further, ADMET screening was conducted which represented Chrysoplenetin as a lead compound. Azithromycin was used as a standard drug. The interactions were studied by PyMol and visualized in LigPlot. Furthermore, the RMSD graph shows fluctuations at various points at the start of simulation in Top1 (Azithromycin) complex system due to structural changes in the helix-coil-helix and beta-turn-beta changes at specific points resulting in increased RMSD with a time frame of 50 ns. But this change remains stable after the extension of simulation time intervals till 100 ns. On other side, the Top2 complex system remains highly stable throughout the time scale. No such structural dynamics were observed bu the ligand attached to the active site residues binds strongly. Conclusion This study facilitates researchers to develop and discover more effective and specific therapeutic agents against SARS-CoV-2 and other viral infections. Finally, chrysoplenetin was identified as a more potent drug candidate to act against the viral main protease, which in the future can be helpful.

Desde o início da pandemia do novo coronavírus, houve grande preocupação diante de uma doença cujos possíveis impactos e morbidade ainda eram desconhecidos, iniciando, assim, uma corrida na descoberta de um tratamento para esta doença. Nesse sentido diversas pesquisas foram e estão sendo realizadas em busca de espécies vegetais passíveis de serem utilizadas na terapêutica da COVID-19. Portanto, esse estudo tem como objetivo realizar revisão de estudos etnodirigidos de espécies vegetais referenciadas na terapêutica e/ou prevenção da COVID-19. Foi realizada uma busca nas bases Scielo, LILACS e PubMed entre 2020 a 2022. Foram selecionados 32 artigos, predominando os de língua inglesa (n= 30), em 2021 (56,25%) e nos países Irã, Índia e Estados Unidos (15,62%); 86 espécies vegetais foram referidas, pertencentes a 51 famílias, com predomínio de Asteraceae e Laminaceae. As espécies mais referidas foram Glycyrrhiza glabra L. (4,65%) e Nigella sativa L. (3,48%), predominando o uso da raiz (29,4 %), preparadas como extrato aquoso (23,5%). Para futuros trabalhos, deve ser estimulada a continuidade dos estudos de validação com tais espécies, fundamentados na certificação de eficácia, segurança e qualidade; afim de minimizar os riscos do uso popular de produto inadequado e contribuir na pesquisa e desenvolvimento de um futuro bioproduto no tratamento do SARS-CoV-2.

In 2020, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) challenged the world with a global outbreak that led to millions of deaths worldwide. Coronavirus disease 2019 (COVID-19) is the symptomatic manifestation of this virus, which can range from flu-like symptoms to utter clinical complications and even death. Since there was no clear medicine that could tackle this infection or lower its complications with minimal adverse effects on the patients’ health, the world health organization (WHO) developed awareness programs to lower the infection rate and limit the fast spread of this virus. Although vaccines have been developed as preventative tools, people still prefer going back to traditional herbal medicine, which provides remarkable health benefits that can either prevent the viral infection or limit the progression of severe symptoms through different mechanistic pathways with relatively insignificant side effects. This comprehensive review provides scientific evidence elucidating the effect of 10 different plants against SARS-CoV-2, paving the way for further studies to reconsider plant-based extracts, rich in bioactive compounds, into more advanced clinical assessments in order to identify their impact on patients suffering from COVID-19.

The emergence of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected many countries throughout the world. As urgency is a necessity, most efforts have focused on identifying small molecule drugs that can be repurposed for use as anti-SARS-CoV-2 agents. Although several drug candidates have been identified using in silico method and in vitro studies, most of these drugs require the support of in vivo data before they can be considered for clinical trials. Several drugs are considered promising therapeutic agents for COVID-19. In addition to the direct-acting antiviral drugs, supportive therapies including traditional Chinese medicine, immunotherapies, immunomodulators, and nutritional therapy could contribute a major role in treating COVID-19 patients. Some of these drugs have already been included in the treatment guidelines, recommendations, and standard operating procedures. In this article, we comprehensively review the approved and potential therapeutic drugs, immune cells-based therapies, immunomodulatory agents/drugs, herbs and plant metabolites, nutritional and dietary for COVID-19.

The outbreak of the new coronavirus (COVID-19) has been transferred exponentially. There are many articles that have found the inhibitory effect of plant extracts or plant compounds on the coronavirus family. In this study, we want to use systematic review and meta-analysis to answer the question of which herbal compound can be more effective against the coronavirus. The present study is based on the guidelines for conducting meta-analyzes. An extensive search was conducted in the electronic database, and based on the inclusion and exclusion criteria, articles were selected and data screening was performed. Quality control of articles was performed. Data analysis was carried out in STATA software. The results showed that alkaloid compounds had a good effect in controlling the coronavirus and reducing viral titer. Trypthantrin, Sambucus extract, S. cusia extract, Boceprevir and Indigole B, dioica agglutinin urtica had a good effect on reducing the virus titer but their selectivity index has not been reported and it is recommended to determine for these compounds. Also among the compounds that had the greatest effect on virus inhibition, including Saikosaponins B2, SaikosaponinsD, SaikosaponinsA and Phillyrin, had an acceptable selectivity index greater than 10. Andrographolide showed the highest selectivity index on SARS-COV2, while virus titration and virus inhibition were not reported. The small number of studies that used alkaloid compounds was one of the limitations and it is suggested to investigate the effect of more alkaloid compounds against the coronavirus for verifying its effect.

AbstractCOVID-19 is an emerging infectious disease and was recently declared as a pandemic by WHO. Currently, there is no vaccine or therapeutic available for this disease. Drug repositioning represents the only feasible option to address this global challenge and a panel of 48 FDA-approved drugs that have been pre-selected by an assay of SARS-CoV was screened to identify potential antiviral drug candidates against SARS-CoV-2 infection. We found a total of 24 drugs which exhibited antiviral efficacy (0.1 μM < IC50 < 10 μM) against SARS-CoV-2. In particular, two FDA-approved drugs - niclosamide and ciclesonide – were notable in some respects. These drugs will be tested in an appropriate animal model for their antiviral activities. In near future, these already FDA-approved drugs could be further developed following clinical trials in order to provide additional therapeutic options for patients with COVID-19.

AbstractDrug repurposing is a rapid approach to identifying therapeutics for the treatment of emerging infectious diseases such as COVID-19. To address the urgent need for treatment options, we carried out a quantitative high-throughput screen using a SARS-CoV-2 cytopathic assay with a compound collection of 8,810 approved and investigational drugs, mechanism-based bioactive compounds, and natural products. Three hundred and nineteen compounds with anti-SARS-CoV-2 activities were identified and confirmed, including 91 approved drug and 49 investigational drugs. Among these confirmed compounds, the anti-SARS-CoV-2 activities of 230 compounds, including 38 approved drugs, have not been previously reported. Chlorprothixene, methotrimeprazine, and piperacetazine were the three most potent FDA approved drugs with anti-SARS-CoV-2 activities. These three compounds have not been previously reported to have anti-SARS-CoV-2 activities, although their antiviral activities against SARS-CoV and Ebola virus have been reported. These results demonstrate that this comprehensive data set of drug repurposing screen for SARS-CoV-2 is useful for drug repurposing efforts including design of new drug combinations for clinical trials.

AbstractRepurposed drugs that block the interaction between the SARS-CoV-2 spike protein and its receptor ACE2 could offer a rapid route to novel COVID-19 treatments or prophylactics. Here, we screened 2701 compounds from a commercial library of drugs approved by international regulatory agencies for their ability to inhibit the binding of recombinant, trimeric SARS-CoV-2 spike protein to recombinant human ACE2. We identified 56 compounds that inhibited binding by <90%, measured the EC50 of binding inhibition, and computationally modeled the docking of the best inhibitors to both Spike and ACE2. These results highlight an effective screening approach to identify compounds capable of disrupting the Spike-ACE2 interaction as well as identifying several potential inhibitors that could serve as templates for future drug discovery efforts.

ABSTRACTCOVID-19 vaccines based on the Spike protein of SARS-CoV-2 have been developed that appear to be largely successful in stopping infection. However, vaccine escape variants might arise leading to a re-emergence of COVID. In anticipation of such a scenario, the identification of repurposed drugs that stop SARS-CoV-2 replication could have enormous utility in stemming the disease. Here, using a nano-luciferase tagged version of the virus (SARS-CoV-2- DOrf7a-NLuc) to quantitate viral load, we evaluated a range of human cell types for their ability to be infected and support replication of the virus, and performed a screen of 1971 FDA-approved drugs. Hepatocytes, kidney glomerulus, and proximal tubule cells were particularly effective in supporting SARS-CoV-2 replication, which is in- line with reported proteinuria and liver damage in patients with COVID-19. We identified 35 drugs that reduced viral replication in Vero and human hepatocytes when treated prior to SARS-CoV-2 infection and found amodiaquine, atovaquone, bedaquiline, ebastine, LY2835219, manidipine, panobinostat, and vitamin D3 to be effective in slowing SARS-CoV-2 replication in human cells when used to treat infected cells. In conclusion, our study has identified strong candidates for drug repurposing, which could prove powerful additions to the treatment of COVID.

AbstractThe ongoing pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), necessitates strategies to identify prophylactic and therapeutic drug candidates for rapid clinical deployment. Here, we describe a screening pipeline for the discovery of efficacious SARS-CoV-2 inhibitors. We screen a best-in-class drug repurposing library, ReFRAME, against two high-throughput, high-content imaging infection assays: one using HeLa cells expressing SARS-CoV-2 receptor ACE2 and the other using lung epithelial Calu-3 cells. From nearly 12,000 compounds, we identify 49 (in HeLa-ACE2) and 41 (in Calu-3) compounds capable of selectively inhibiting SARS-CoV-2 replication. Notably, most screen hits are cell-line specific, likely due to different virus entry mechanisms or host cell-specific sensitivities to modulators. Among these promising hits, the antivirals nelfinavir and the parent of prodrug MK-4482 possess desirable in vitro activity, pharmacokinetic and human safety profiles, and both reduce SARS-CoV-2 replication in an orthogonal human differentiated primary cell model. Furthermore, MK-4482 effectively blocks SARS-CoV-2 infection in a hamster model. Overall, we identify direct-acting antivirals as the most promising compounds for drug repurposing, additional compounds that may have value in combination therapies, and tool compounds for identification of viral host cell targets.

Introduction: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. No drug has been generally approved as safe and effective for the treatment of COVID-19. Several therapeutic agents such as COVID Organics® (CVO) have been explored as treatment options. CVO is an herbal tea composed of 62% of Artemisia annua and 38% of other plants. There is presently no existing scientific report and data on the safety and efficacy of CVO herbal drug. Thus, acute and subacute toxicity studies were undertaken to evaluate the safety and toxicity of CVO on short- and long-term usage in animal models. Materials and Methods: Phytochemical and nutritional compositions of CVO were determined using standard methods. Acute oral toxicity was investigated using female Swiss albino mice (three per group). While subacute oral toxicity was done using female and male Swiss albino rats (five per group). The animals were administered 2000 mg/kg, 5000 mg/kg, therapeutic dose; 5500 mg/kg and supratherapeutic dose; 11,000 mg/kg of CVO herbal product. The control group received water ad libitum. The oral toxicity studies were done in accordance with Organization for Economic Corporation and Development guidelines. The experimental protocol was approved by the Institutional Animal Care and Use Committee, Nigerian Institute of Medical Research (Ethics No. IRB/17/043). Results: CVO is rich in antioxidants: flavonoids (10.3%), tannins (29.1%), and phenolics (434.4 mg). It contains proteins (33.8%), carbohydrates (34.5%), fat (6.8%), and fiber (0.5%). In the acute toxicity study, no mortality was recorded in all the treated and untreated groups. The lethal dose of CVO is >5000 mg/kg body weight. The hematological, biochemical, lipid profile, and histologic parameters were all normal at therapeutic doses when compared to the control group. Conclusion: The acute and subacute oral toxicity studies revealed that CVO is not toxic. The specific organ toxicity evaluations also indicated that CVO has no toxic effects on blood parameters and vital organs structure and function at therapeutic dose. Thus, CVO is safe for short- and long-term usage. We recommend that CVO should be subjected to efficacy studies to investigate whether it is effective for COVID-19 treatment as claimed by the manufacturer.

Amid the SARS‐CoV‐2 pandemic, herbal medicines have received much attention in its evidence-based therapeutics. Scientists across the globe are integrating new research at an unprecedented fast pace for the discovery of novel molecules against this deadly viral disease. Ever since ancient times, phytochemicals have long been used traditionally for the cure of many viral diseases and lately many are being tested for their potential against the viral replications/transcriptions. The unmatched structural diversity of phytoconstituents may prove to be a gold mine for antiviral drug discovery. Many plants like Heteromorpha spp., Bupleurum spp, Scrophularia scorodonia, Artemisia annua, Pyrrosia lingua, Lycoris radiate, and Lindera agregata have also been reported to have antiviral potential against SARS-CoV. Recently many synthetic molecules like remdesivir, tocilizumab, favipirapir, dexamethasone, glucocorticoid, and hydroxychloroquine etc. have been extensively investigated for their potential against the SARS‐CoV‐2, likewise, various plant-based molecules such as scutellarein, silvestrol, tryptanthrin, saikosaponin B2, quercetin, myricetin, caffeic acid, psoralidin, isobavachalcone, and lectins-griffiths in were also found to be equally effective. Needless to mention that, the herbal medicines are a valuable and powerful source of chemical compounds which need further chemical modifications and appropriate in-vitro and in-vivo testings for establishing their safety and efficacy as potential drugs against the battle with coronavirus pandemic. In this review, we will try to highlight the potential phytochemicals candidates with their possible molecular targets against the SARS‐CoV‐2and demystify the myths behind the purported remedies such as herbal therapies, teas, essential oils, tinctures, and silver products such as colloidal silver that have no scientific evidence to prevent or cure COVID-19. Apart from that, this review will also de-fabricate the surgency of objectionable claims that are continuously reckoning towards the treatment of COVID-19 with hundred per cent surety and are propagated by several herbal firms.

Background The global pandemics of severe acute respiratory syndrome, Middle East respiratory syndrome, and COVID-19 have caused unprecedented crises for public health. Coronaviruses are constantly evolving, and it is unknown which new coronavirus will emerge and when the next coronavirus will sweep across the world. Knowledge graphs are expected to help discover the pathogenicity and transmission mechanism of viruses. Objective The aim of this study was to discover potential targets and candidate drugs to repurpose for coronaviruses through a knowledge graph–based approach. Methods We propose a computational and evidence-based knowledge discovery approach to identify potential targets and candidate drugs for coronaviruses from biomedical literature and well-known knowledge bases. To organize the semantic triples extracted automatically from biomedical literature, a semantic conversion model was designed. The literature knowledge was associated and integrated with existing drug and gene knowledge through semantic mapping, and the coronavirus knowledge graph (CovKG) was constructed. We adopted both the knowledge graph embedding model and the semantic reasoning mechanism to discover unrecorded mechanisms of drug action as well as potential targets and drug candidates. Furthermore, we have provided evidence-based support with a scoring and backtracking mechanism. Results The constructed CovKG contains 17,369,620 triples, of which 641,195 were extracted from biomedical literature, covering 13,065 concept unique identifiers, 209 semantic types, and 97 semantic relations of the Unified Medical Language System. Through multi-source knowledge integration, 475 drugs and 262 targets were mapped to existing knowledge, and 41 new drug mechanisms of action were found by semantic reasoning, which were not recorded in the existing knowledge base. Among the knowledge graph embedding models, TransR outperformed others (mean reciprocal rank=0.2510, Hits@10=0.3505). A total of 33 potential targets and 18 drug candidates were identified for coronaviruses. Among them, 7 novel drugs (ie, quinine, nelfinavir, ivermectin, asunaprevir, tylophorine, Artemisia annua extract, and resveratrol) and 3 highly ranked targets (ie, angiotensin converting enzyme 2, transmembrane serine protease 2, and M protein) were further discussed. Conclusions We showed the effectiveness of a knowledge graph–based approach in potential target discovery and drug repurposing for coronaviruses. Our approach can be extended to other viruses or diseases for biomedical knowledge discovery and relevant applications.

Drug repositioning is the only feasible option to immediately address the COVID-19 global challenge. We screened a panel of 48 FDA-approved drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which were preselected by an assay of SARS-CoV. We identified 24 potential antiviral drug candidates against SARS-CoV-2 infection. Some drug candidates showed very low 50% inhibitory concentrations (IC 50 s), and in particular, two FDA-approved drugs—niclosamide and ciclesonide—were notable in some respects.

There are no FDA-approved antivirals for any coronavirus, including SARS-CoV-2. Numerous drugs are already approved for human use that may have antiviral activity and therefore could potentially be rapidly repurposed as antivirals. Here, we present data assessing the antiviral activity of 20 FDA-approved drugs against SARS-CoV-2 that also inhibit SARS-CoV and MERS-CoV in vitro . We found that 17 of these inhibit SARS-CoV-2, suggesting that they may have pan-anti-coronaviral activity. We directly followed up seven of these and found that they all inhibit infectious-SARS-CoV-2 production. Moreover, we evaluated chloroquine and chlorpromazine in vivo using mouse-adapted SARS-CoV. We found that neither drug inhibited viral replication in the lungs, but both protected against clinical disease.

Repurposed drugs that block the interaction between the SARS-CoV-2 spike protein and its receptor ACE2 could offer a rapid route to novel COVID-19 treatments or prophylactics. Here, we screened 2,701 compounds from a commercial library of drugs approved by international regulatory agencies for their ability to inhibit the binding of recombinant, trimeric SARS-CoV-2 spike protein to recombinant human ACE2. We identified 56 compounds that inhibited binding in a concentration-dependent manner, measured the IC50of binding inhibition, and computationally modeled the docking of the best inhibitors to the Spike-ACE2 binding interface. The best candidates were Thiostrepton, Oxytocin, Nilotinib, and Hydroxycamptothecin with IC50’s in the 4–9 μM range. These results highlight an effective screening approach to identify compounds capable of disrupting the Spike-ACE2 interaction, as well as identify several potential inhibitors of the Spike-ACE2 interaction.

COVID-19 vaccines based on the Spike protein of SARS-CoV-2 have been developed that appear to be largely successful in stopping infection. However, therapeutics that can help manage the disease are still required until immunity has been achieved globally. The identification of repurposed drugs that stop SARS-CoV-2 replication could have enormous utility in stemming the disease. Here, using a nano-luciferase tagged version of the virus (SARS-CoV-2-ΔOrf7a-NLuc) to quantitate viral load, we evaluated a range of human cell types for their ability to be infected and support replication of the virus, and performed a screen of 1971 FDA-approved drugs. Hepatocytes, kidney glomerulus, and proximal tubule cells were particularly effective in supporting SARS-CoV-2 replication, which is in-line with reported proteinuria and liver damage in patients with COVID-19. Using the nano-luciferase as a measure of virus replication we identified 35 drugs that reduced replication in Vero cells and human hepatocytes when treated prior to SARS-CoV-2 infection and found amodiaquine, atovaquone, bedaquiline, ebastine, LY2835219, manidipine, panobinostat, and vitamin D3 to be effective in slowing SARS-CoV-2 replication in human cells when used to treat infected cells. In conclusion, our study has identified strong candidates for drug repurposing, which could prove powerful additions to the treatment of COVID.

Abstract Serious illnesses caused by viruses are becoming the world’s most critical public health issues and lead millions of deaths each year in the world. Thousands of studies confirmed that the plant-derived medicines could play positive therapeutic effects on the patients with viral diseases. Since thousands of antiviral phytochemicals have been identified as lifesaving drugs in medical research, a comprehensive database is highly desirable to integrate the medicinal plants with their different medicinal properties. Therefore, we provided a friendly antiviral phytochemical database AVPCD covering 2537 antiviral phytochemicals from 383 medicinal compounds and 319 different families with annotation of their scientific, family and common names, along with the parts used, disease information, active compounds, links of relevant articles for COVID-19, cancer, HIV and malaria. Furthermore, each compound in AVPCD was annotated with its 2D and 3D structure, molecular formula, molecular weight, isomeric SMILES, InChI, InChI Key and IUPAC name and 21 other properties. Each compound was annotated with more than 20 properties. Specifically, a scoring method was designed to measure the confidence of each phytochemical for the viral diseases. In addition, we constructed a user-friendly platform with several powerful modules for searching and browsing the details of all phytochemicals. We believe this database will facilitate global researchers, drug developers and health practitioners in obtaining useful information against viral diseases.

The ongoing COVID-19 pandemic has resulted in a global panic because of its continual evolution and recurring spikes. This serious malignancy is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the outbreak, millions of people have been affected from December 2019 till now, which has led to a great surge in finding treatments. Despite trying to handle the pandemic with the repurposing of some drugs, such as chloroquine, hydroxychloroquine, remdesivir, lopinavir, ivermectin, etc., against COVID-19, the SARS-CoV-2 virus continues its out-of-control spread. There is a dire need to identify a new regimen of natural products to combat the deadly viral disease. This article deals with the literature reports to date of natural products showing inhibitory activity towards SARS-CoV-2 through different approaches, such as in vivo, in vitro, and in silico studies. Natural compounds targeting the proteins of SARS-CoV-2—the main protease (Mpro), papain-like protease (PLpro), spike proteins, RNA-dependent RNA polymerase (RdRp), endoribonuclease, exoribonuclease, helicase, nucleocapsid, methyltransferase, adeno diphosphate (ADP) phosphatase, other nonstructural proteins, and envelope proteins—were extracted mainly from plants, and some were isolated from bacteria, algae, fungi, and a few marine organisms.

Despite the fact that coronavirus disease 2019 (COVID-19) treatment and management are now considerably regulated, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still one of the leading causes of death in 2022. The availability of COVID-19 vaccines, FDA-approved antivirals, and monoclonal antibodies in low-income countries still poses an issue to be addressed. Natural products, particularly traditional Chinese medicines (TCMs) and medicinal plant extracts (or their active component), have challenged the dominance of drug repurposing and synthetic compound libraries in COVID-19 therapeutics. Their abundant resources and excellent antiviral performance make natural products a relatively cheap and readily available alternative for COVID-19 therapeutics. Here, we deliberately review the anti-SARS-CoV-2 mechanisms of the natural products, their potency (pharmacological profiles), and application strategies for COVID-19 intervention. In light of their advantages, this review is intended to acknowledge the potential of natural products as COVID-19 therapeutic candidates.

AbstractThe recent outbreak of the COVID-19 pandemic caused by severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2) has shown the necessity for fast and broad drug discovery methods to enable us to react quickly to novel and highly infectious diseases. A well-known SARS-CoV-2 target is the viral main 3-chymotrypsin-like cysteine protease (Mpro), known to control coronavirus replication, which is essential for the viral life cycle. Here, we applied an interaction-based drug repositioning algorithm on all protein-compound complexes available in the protein database (PDB) to identify Mpro inhibitors and potential novel compound scaffolds against SARS-CoV-2. The screen revealed a heterogeneous set of 692 potential Mpro inhibitors containing known ones such as Dasatinib, Amodiaquine, and Flavin mononucleotide, as well as so far untested chemical scaffolds. In a follow-up evaluation, we used publicly available data published almost two years after the screen to validate our results. In total, we are able to validate 17% of the top 100 predictions with publicly available data and can furthermore show that predicted compounds do cover scaffolds that are yet not associated with Mpro. Finally, we detected a potentially important binding pattern consisting of 3 hydrogen bonds with hydrogen donors of an oxyanion hole within the active side of Mpro. Overall, these results give hope that we will be better prepared for future pandemics and that drug development will become more efficient in the upcoming years.

The rapid spread of the new coronavirus disease (COVID-19) caused by SARS-CoV-2 has become a global pandemic. Although specific vaccines are available and natural drugs are being researched, supportive care and specific treatments to alleviate symptoms and improve patient quality of life remain critical. Chinese medicine (CM) has been employed in China due to the similarities between the epidemiology, genomics, and pathogenesis of SARS-CoV-2 and SARS-CoV. Moreover, the integration of other traditional oriental medical systems into the broader framework of integrative medicine can offer a powerful approach to managing the disease. Additionally, it has been reported that integrated medicine has better effects and does not increase adverse drug reactions in the context of COVID-19. This article examines preventive measures, potential infection mechanisms, and immune responses in Western medicine (WM), as well as the pathophysiology based on principles of complementary medicine (CM). The convergence between WM and CM approaches, such as the importance of maintaining a strong immune system and promoting preventive care measures, is also addressed. Current treatment options, traditional therapies, and classical prescriptions based on empirical knowledge are also explored, with individual patient circumstances taken into account. An analysis of the potential benefits and challenges associated with the integration of complementary and Western medicine (WM) in the treatment of COVID-19 can provide valuable guidance, enrichment, and empowerment for future research endeavors.

According to the World Health Organization (WHO), in the second half of 2022, there are about 606 million confirmed cases of COVID-19 and almost 6,500,000 deaths around the world. A pandemic was declared by the WHO in March 2020 when the new coronavirus spread around the world. The short time between the first cases in Wuhan and the declaration of a pandemic initiated the search for ways to stop the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or to attempt to cure the disease COVID-19. More than ever, research groups are developing vaccines, drugs, and immunobiological compounds, and they are even trying to repurpose drugs in an increasing number of clinical trials. There are great expectations regarding the vaccine’s effectiveness for the prevention of COVID-19. However, producing sufficient doses of vaccines for the entire population and SARS-CoV-2 variants are challenges for pharmaceutical industries. On the contrary, efforts have been made to create different vaccines with different approaches so that they can be used by the entire population. Here, we summarize about 8162 clinical trials, showing a greater number of drug clinical trials in Europe and the United States and less clinical trials in low-income countries. Promising results about the use of new drugs and drug repositioning, monoclonal antibodies, convalescent plasma, and mesenchymal stem cells to control viral infection/replication or the hyper-inflammatory response to the new coronavirus bring hope to treat the disease.

COVID-19 pandemic caused by the novel SARS-CoV-2 has impacted human livelihood globally. Strenuous efforts have been employed for its control and prevention; however, with recent reports on mutated strains with much higher infectivity, transmissibility, and ability to evade immunity developed from previous SARS-CoV-2 infections, prevention alternatives must be prepared beforehand in case. We have perused over 128 recent works (found on Google Scholar, PubMed, and ScienceDirect as of February 2023) on medicinal plants and their compounds for anti-SARS-CoV-2 activity and eventually reviewed 102 of them. The clinical application and the curative effect were reported high in China and in India. Accordingly, this review highlights the unprecedented opportunities offered by medicinal plants and their compounds, candidates as the therapeutic agent, against COVID-19 by acting as viral protein inhibitors and immunomodulator in (32 clinical trials and hundreds of in silico experiments) conjecture with modern science. Moreover, the associated foreseeable challenges for their viral outbreak management were discussed in comparison to synthetic drugs.

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a profound impact on the world’s health and economy. Although the end of the pandemic may come in 2023, it is generally believed that the virus will not be completely eradicated. Most likely, the disease will become an endemicity. The rapid development of vaccines of different types (mRNA, subunit protein, inactivated virus, etc.) and some other antiviral drugs (Remdesivir, Olumiant, Paxlovid, etc.) has provided effectiveness in reducing COVID-19’s impact worldwide. However, the circulating SARS-CoV-2 virus has been constantly mutating with the emergence of multiple variants, which makes control of COVID-19 difficult. There is still a pressing need for developing more effective antiviral drugs to fight against the disease. Plants have provided a promising production platform for both bioactive chemical compounds (small molecules) and recombinant therapeutics (big molecules). Plants naturally produce a diverse range of bioactive compounds as secondary metabolites, such as alkaloids, terpenoids/terpenes and polyphenols, which are a rich source of countless antiviral compounds. Plants can also be genetically engineered to produce valuable recombinant therapeutics. This molecular farming in plants has an unprecedented opportunity for developing vaccines, antibodies, and other biologics for pandemic diseases because of its potential advantages, such as low cost, safety, and high production volume. This review summarizes the latest advancements in plant-derived drugs used to combat COVID-19 and discusses the prospects and challenges of the plant-based production platform for antiviral agents.

Context: The whole universe is facing a coronavirus catastrophe, and prompt treatment for the health crisis is primarily significant. The primary way to improve health conditions in this battle is to boost our immunity and alter our diet patterns. A common bulb veggie used to flavor cuisine is garlic. Compounds in the plant that are physiologically active are present, contributing to its pharmacological characteristics. Among several food items with nutritional value and immunity improvement, garlic stood predominant and more resourceful natural antibiotic with a broad spectrum of antiviral potency against diverse viruses. However, earlier reports have depicted its efficacy in the treatment of a variety of viral illnesses. Nonetheless, there is no information on its antiviral activities and underlying molecular mechanisms. Objectives: The bioactive compounds in garlic include organosulfur (allicin and alliin) and flavonoid (quercetin) compounds. These compounds have shown immunomodulatory effects and inhibited attachment of coronavirus to the angiotensin-converting enzyme 2 (ACE2) receptor and the Mpro of SARS-CoV-2. Further, we have discussed the contradictory impacts of garlic used as a preventive measure against the novel coronavirus. Method: The GC/MS analysis revealed 18 active chemicals, including 17 organosulfur compounds in garlic. Using the molecular docking technique, we report for the first time the inhibitory effect of the under-consideration compounds on the host receptor ACE2 protein in the human body, providing a crucial foundation for understanding individual compound coronavirus resistance on the main protease protein of SARS-CoV-2. Allyl disulfide and allyl trisulfide, which make up the majority of the compounds in garlic, exhibit the most potent activity. Results: Conventional medicine has proven its efficiency from ancient times. Currently, our article's prime spotlight was on the activity of Allium sativum on the relegation of viral load and further highlighted artificial intelligence technology to study the attachment of the allicin compound to the SARS-CoV-2 receptor to reveal its efficacy. Conclusions: The COVID-19 pandemic has triggered interest among researchers to conduct future research on molecular docking with clinical trials before releasing salutary remedies against the deadly malady.