scholarly journals Echinacea as a Potential Force against Coronavirus Infections? A Mini-Review of Randomized Controlled Trials in Adults and Children

2021 ◽  
Author(s):  
Simon Nicolussi ◽  
Karin Ardjomand-Woelkart ◽  
Rainer Stange ◽  
Giuseppe Gancitano ◽  
Peter Klein ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Echinacea Purpurea ◽  
Respiratory Pathogens ◽  
Virus Infections ◽  
Potential Force ◽  
Viral Loads ◽  
Enveloped Virus ◽  
Adults And Children ◽  
Coronavirus Infections

Echinacea purpurea was shown to broadly inhibit coronaviruses and SARS-CoV-2 in vitro. This review discusses the available clinical evidence from randomized, blinded and controlled human studies. Two RCTs with results on enveloped viruses, respectively coronavirus infections during prevention treatment were detected. Incidence and/or viral loads were measured by RT-PCR and symptom severity was recorded. Jawad et al. (2012) collected nasopharyngeal swabs from adults (N=755) over 4 months of continuous prevention. Overall, 24 and 47 enveloped virus infections occurred, including 21 and 33 coronavirus detections [229E; HKU1; OC43] with Echinaforce extract [2400mg daily] and placebo, respectively (p=0.0114). Ogal et al. (2021) administered the same extract [1200mg] or control for 4 months to children (4-12 years) (N=203). Echinacea reduced the incidence of enveloped virus infections from 47 to 29 (p=0.0038) whereas 11 and 13 coronavirus detections [229E, OC43, NL63] were counted (p>0.05). Respiratory symptoms during coronavirus infections were significantly lower with area-under-curve AUC=75.8 (+/-50.24) versus 27.1 (+/-21.27) score points (p=0.0036). Importantly, viral loads in nasal secretions were significantly reduced by 98.5%, with Ct-values 31.1 [95% CI 26.3; 35.9] versus 25.0 [95% CI 20.5; 29.5] (p = 0.0479). Results from clinical studies confirm the antiviral activity found for Echinacea in vitro, embracing enveloped respiratory pathogens and therefore coronaviruses as well. Substantiating results from a new completed study seems to extrapolate these effects to the prevention of SARS-CoV-2 infection. As hypothesized, the testified broad antiviral activity of Echinacea extract appears to be inclusive for SARS-CoV-2.

scholarly journals In Vitro Inhibition of Zika Virus Replication with Amantadine and Rimantadine Hydrochlorides

2021 ◽  
Vol 12 (3) ◽  
pp. 727-738
Author(s):  
Jorge L. Arias-Arias ◽  
Francisco Vega-Aguilar ◽  
Dihalá Picado-Soto ◽  
Eugenia Corrales-Aguilar ◽  
Gilbert D. Loría
Keyword(s):  
Antiviral Activity ◽  
Zika Virus ◽  
Influenza A ◽  
Yellow Fever Virus ◽  
Human Infection ◽  
Virus Infections ◽  
Drug Concentrations ◽  
Dose Dependent ◽  
Reference Strains

Zika virus (ZIKV) is a mosquito-borne flavivirus in which human infection became relevant during recent outbreaks in Latin America due to its unrecognized association with fetal neurological disorders. Currently, there are no approved effective antivirals or vaccines for the treatment or prevention of ZIKV infections. Amantadine and rimantadine are approved antivirals used against susceptible influenza A virus infections that have been shown to have antiviral activity against other viruses, such as dengue virus (DENV). Here, we report the in vitro effectiveness of both amantadine and rimantadine hydrochlorides against ZIKV replication, resulting in a dose-dependent reduction in viral titers of a ZIKV clinical isolate and two different ZIKV reference strains. Additionally, we demonstrate similar in vitro antiviral activity of these drugs against DENV-1 and yellow fever virus (YFV), although at higher drug concentrations for the latter. ZIKV replication was inhibited at drug concentrations well below cytotoxic levels of both compounds, as denoted by the high selectivity indexes obtained with the tested strains. Further work is absolutely needed to determine the potential clinical use of these antivirals against ZIKV infections, but our results suggest the existence of a highly conserved mechanism across flavivirus, susceptible to be blocked by modified more specific adamantane compounds.

scholarly journals SARS-CoV-2 Mpro inhibitors with antiviral activity in a transgenic mouse model

Science ◽  
2021 ◽  
pp. eabf1611
Author(s):  
Jingxin Qiao ◽  
Yue-Shan Li ◽  
Rui Zeng ◽  
Feng-Liang Liu ◽  
Rong-Hua Luo ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Transgenic Mouse Model ◽  
Global Public Health ◽  
Viral Loads ◽  
Main Protease ◽  
Pharmacokinetic Properties ◽  
Intraperitoneal Treatment

The COVID-19 pandemic caused by the SARS-CoV-2 virus continually poses serious threats to global public health. The main protease (Mpro) of SARS-CoV-2 plays a central role in viral replication. We designed and synthesized 32 new bicycloproline-containing Mpro inhibitors derived from either Boceprevir or Telaprevir, both of which are approved antivirals. All compounds inhibited SARS-CoV-2 Mpro activity in vitro with IC50 values ranging from 7.6 to 748.5 nM. The co-crystal structure of Mpro in complex with MI-23, one of the most potent compounds, revealed its interaction mode. Two compounds (MI-09 and MI-30) showed excellent antiviral activity in cell-based assays. In a SARS-CoV-2 infection transgenic mouse model, oral or intraperitoneal treatment with MI-09 or MI-30 significantly reduced lung viral loads and lung lesions. Both also displayed good pharmacokinetic properties and safety in rats.

scholarly journals Lambda Interferon (IFN-λ), a Type III IFN, Is Induced by Viruses and IFNs and Displays Potent Antiviral Activity against Select Virus Infections In Vivo

2006 ◽  
Vol 80 (9) ◽  
pp. 4501-4509 ◽  
Author(s):  
Nina Ank ◽  
Hans West ◽  
Christina Bartholdy ◽  
Kristina Eriksson ◽  
Allan R. Thomsen ◽  
...  
Keyword(s):  
Viral Load ◽  
Antiviral Activity ◽  
Encephalomyocarditis Virus ◽  
In Vitro Assays ◽  
Vaginal Mucosa ◽  
Virus Infections ◽  
Type Iii ◽  
Potent Antiviral Activity

ABSTRACT Type III interferons (IFNs) (interleukin-28/29 or lambda interferon [IFN-λ]) are cytokines with IFN-like activities. Here we show that several classes of viruses induce expression of IFN-λ1 and -λ2/3 in similar patterns. The IFN-λs were—unlike alpha/beta interferon (IFN-α/β)—induced directly by stimulation with IFN-α or -λ, thus identifying type III IFNs as IFN-stimulated genes. In vitro assays revealed that IFN-λs have appreciable antiviral activity against encephalomyocarditis virus (EMCV) but limited activity against herpes simplex virus type 2 (HSV-2), whereas IFN-α potently restricted both viruses. Using three murine models for generalized virus infections, we found that while recombinant IFN-α reduced the viral load after infection with EMCV, lymphocytic choriomeningitis virus (LCMV), and HSV-2, treatment with recombinant IFN-λ in vivo did not affect viral load after infection with EMCV or LCMV but did reduce the hepatic viral titer of HSV-2. In a model for a localized HSV-2 infection, we further found that IFN-λ completely blocked virus replication in the vaginal mucosa and totally prevented development of disease, in contrast to IFN-α, which had a more modest antiviral activity. Finally, pretreatment with IFN-λ enhanced the levels of IFN-γ in serum after HSV-2 infection. Thus, type III IFNs are expressed in response to most viruses and display potent antiviral activity in vivo against select viruses. The discrepancy between the observed antiviral activity in vitro and in vivo may suggest that IFN-λ exerts a significant portion of its antiviral activity in vivo via stimulation of the immune system rather than through induction of the antiviral state.

scholarly journals In Vitro and In Vivo Antiviral Activity of Nylidrin by Targeting the Hemagglutinin 2-Mediated Membrane Fusion of Influenza A Virus

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 581 ◽  
Author(s):  
Yejin Jang ◽  
Jin Soo Shin ◽  
Joo-Youn Lee ◽  
Heegwon Shin ◽  
Sang Jick Kim ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Membrane Fusion ◽  
Influenza A Virus ◽  
Influenza A ◽  
Intracellular Localization ◽  
Pharmacophore Modeling ◽  
Respiratory Pathogens ◽  
Antiviral Compound

Influenza A virus, one of the major human respiratory pathogens, is responsible for annual seasonal endemics and unpredictable periodic pandemics. Despite the clinical availability of vaccines and antivirals, the antigenic diversity and drug resistance of this virus makes it a persistent threat to public health, underlying the need for the development of novel antivirals. In a cell culture-based high-throughput screen, a β2-adrenergic receptor agonist, nylidrin, was identified as an antiviral compound against influenza A virus. The molecule was effective against multiple isolates of subtype H1N1, but had limited activity against subtype H3N2, depending on the strain. By examining the antiviral activity of its chemical analogues, we found that ifenprodil and clenbuterol also had reliable inhibitory effects against A/H1N1 strains. Field-based pharmacophore modeling with comparisons of active and inactive compounds revealed the importance of positive and negative electrostatic patterns of phenyl aminoethanol derivatives. Time-of-addition experiments and visualization of the intracellular localization of nucleoprotein NP demonstrated that an early step of the virus life cycle was suppressed by nylidrin. Ultimately, we discovered that nylidrin targets hemagglutinin 2 (HA2)-mediated membrane fusion by blocking conformational change of HA at acidic pH. In a mouse model, preincubation of a mouse-adapted influenza A virus (H1N1) with nylidrin completely blocked intranasal viral infection. The present study suggests that nylidrin could provide a core chemical skeleton for the development of a direct-acting inhibitor of influenza A virus entry.

scholarly journals In vitro antiviral activity of Echinaforce®, an Echinacea purpurea preparation, against common cold coronavirus 229E and highly pathogenic MERS-CoV and SARS-CoV

2020 ◽  
Author(s):  
Johanna Signer ◽  
Hulda R. Jonsdottir ◽  
Werner C. Albrich ◽  
Marc Strasser ◽  
Roland Züst ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Common Cold ◽  
Natural Infection ◽  
Gastrointestinal Symptoms ◽  
Case Fatality ◽  
Echinacea Purpurea ◽  
Marginal Effect ◽  
Virus Propagation ◽  
Highly Pathogenic

Abstract Coronaviruses (CoVs) were long thought to only cause mild respiratory and gastrointestinal symptoms in humans but recent outbreaks of Middle Eastern Respiratory Syndrome (MERS)-CoV, Severe Acute Respiratory Syndrome (SARS)-CoV, and the newly identified SARS-CoV-2 have cemented their zoonotic potential and their capacity to cause serious morbidity and mortality, with case fatality rates ranging from 2 to 35%. Currently, no specific prophylaxis or treatment is available for CoV infections and therefore we investigated the antiviral potential of Echinacea purpurea (Echinaforce®) against human coronavirus (HCoV) 229E and the highly pathogenic MERS- and SARS-CoVs in vitro. We found that HCoV-229E was irreversibly inactivated when exposed to Echinaforce at 3.2µg/ml IC50. Pre-treatment of cell lines, however, did not inhibit infection with HCoV-229E and post-infection treatment had only a marginal effect on virus propagation at 50 µg/ml. However, we did observe a protective effect in an organotypic respiratory cell culture system by exposing pre-treated respiratory epithelium to droplets of HCoV-229E, imitating a natural infection. Finally, antiviral activity was not restricted to common cold coronaviruses, as the highly pathogenic SARS- and MERS-CoVs were inactivated at comparable concentrations. These results suggest that Echinacea purpurea preparations, such as Echinaforce, could be effective as prophylactic treatment for all CoVs, including newly occurring strains, such as SARS-CoV-2.

scholarly journals In vitro antiviral activity of Echinaforce®, an Echinacea purpurea preparation, against common cold coronavirus 229E and highly pathogenic MERS-CoV and SARS-CoV

2020 ◽  
Author(s):  
Johanna Signer ◽  
Hulda Run Jonsdottir ◽  
Werner C. Albrich ◽  
Marc Strasser ◽  
Roland Züst ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Protective Effect ◽  
Common Cold ◽  
Post Infection ◽  
Natural Infection ◽  
Gastrointestinal Symptoms ◽  
Echinacea Purpurea ◽  
Marginal Effect ◽  
Highly Pathogenic

Abstract Background: Coronaviruses (CoVs) were long thought to only cause mild respiratory and gastrointestinal symptoms in humans but recent outbreaks of Middle Eastern Respiratory Syndrome (MERS)-CoV, Severe Acute Respiratory Syndrome (SARS)-CoV, and the newly identified SARS-CoV-2 have cemented their zoonotic potential and their capacity to cause serious morbidity and mortality, with case fatality rates ranging from 2 to 35%. Currently, no specific prophylaxis or treatment is available for CoV infections and therefore we investigated the antiviral potential of Echinacea purpurea (Echinaforce®) against human coronavirus (HCoV) 229E and the highly pathogenic MERS- and SARS-CoVs in vitro.Methods:To evaluate the antiviral potential of Echinaforce we pre-treated virus particles and cells and evaluated remaining infectivity by limited dilution. Furthermore, we exposed cells to the extract post-infection to further estimate its potential as a prophylaxis and treatment against coronaviruses. We also determined the protective effect of Echinaforce in re-constituted nasal epithelium.Results:We found that HCoV-229E was irreversibly inactivated when exposed to Echinaforce at 3.2mg/ml IC50. Pre-treatment of cell lines, however, did not inhibit infection with HCoV-229E and post-infection treatment had only a marginal effect on virus propagation at 50 mg/ml. However, we did observe a protective effect in an organotypic respiratory cell culture system by exposing pre-treated respiratory epithelium to droplets of HCoV-229E, imitating a natural infection. Finally, antiviral activity was not restricted to common cold coronaviruses, as the highly pathogenic SARS- and MERS-CoVs were inactivated at comparable concentrations.Conclusions:These results suggest that Echinacea purpurea preparations, such as Echinaforce, could be effective as prophylactic treatment for all CoVs, including newly occurring strains, such as SARS-CoV-2.

scholarly journals Potencial uso terapéutico de las plantas medicinales y sus derivados frente a los coronavirus

2020 ◽  
Vol 5 (3) ◽  
pp. 1
Author(s):  
Marco Orlando Fuel Herrera ◽  
Sandra Cangui Panchi
Keyword(s):  
Medicinal Plants ◽  
Antiviral Activity ◽  
Traditional Medicine ◽  
Urtica Dioica ◽  
Chemical Diversity ◽  
Cochrane Library ◽  
Economic Losses ◽  
Scientific Publications ◽  
Coronavirus Infections

  Las pandemias causadas por los coronavirus afectan a la población y han cobrado miles de vidas y pérdidas económicas en todo el mundo, hasta la presente fecha no hay medicamentos antivirales, vacunas o terapias con anticuerpos monoclonales clínicamente aprobados para tratar sus infecciones. Por otro lado, los compuestos derivados de plantas poseen una gran diversidad química que incluye actividad antiviral por lo que pueden tener utilidad como agentes terapéuticos contra las infecciones por coronavirus. El objetivo fue identificar las plantas medicinales y sus derivados que presentan actividad antiviral in vitro frente a infecciones por coronavirus para lo cual se llevó a cabo una revisión y análisis bibliométrico de las publicaciones científicas de cuatro bases de datos (Medline, Web of Sciense, Scopus y Cochrane Library). Se consideró como adecuado el uso de los descriptores: plantas medicinales, medicina tradicional, fitoquímicos, medicina a base de hierbas, coronavirus, SARS o MERS y se ajustó adecuadamente la ecuación en cada una de ellas. De los 1483 estudios recuperados, tras aplicar los criterios de inclusión y exclusión se seleccionaron 32 artículos, en la mayoría de los estudios se describió el efecto protector por parte de los extractos y sus derivados, destacándose los compuestos: ácido cafeico, xantoangelol B, isobavachalcona, psoralidina, hirsutenona, hirsutanonol, 3β-friedelanol, silvestrol, amentoflavona, ferruginol, savinin, ácido betulínico, urtica dioica, griffithsia, taraxerol, ácido clorogénico por sus propiedades para inhibir proteínas estructurales y de unión a los receptores del huésped, así como la inhibición de proteasas importantes en la división y replicación del virus.   Palabra clave: Plantas medicinales, medicina tradicional, agentes antivirales, coronavirus.   Abstract Pandemics caused by coronaviruses affect the population and have claimed thousands of lives and economic losses worldwide. To date, there are no antiviral drugs, vaccines, or monoclonal antibody therapies clinically approved to treat their infections. On the other hand, plant-derived compounds have a great chemical diversity that includes antiviral activity and therefore may be useful as therapeutic agents against coronavirus infections. The objective was to identify the medicinal plants and their derivatives that present antiviral activity in vitro against coronavirus infections. A bibliometric review and analysis of the scientific publications of four databases (Medline, Web of Science, Scopus, and Cochrane Library) was carried out, and the use of the descriptors was considered appropriate: medicinal plants, traditional medicine, phytochemicals, herbal medicine, coronavirus, SARS or MERS and the equation in each of them was adjusted accordingly. Of the 1483 studies retrieved, after applying the inclusion and exclusion criteria, 32 articles were selected. In most of the studies, the protective effect by the extracts and their derivatives was described, highlighting the compounds: caffeic acid, xanthoangelol B, isobavachalcone, psoralidin, hirsutenone, hirsutanonol, 3β-friedelanol, silvestrol, amentoflavone, ferruginol, savinin, betulinic acid, urtica dioica, griffithsia, taraxerol, chlorogenic acid for their properties to inhibit structural and host receptor binding proteins, as well as the inhibition of important proteases in virus division and replication.   Keywords: Medicinal plants, traditional medicine, acting antiviral agents, coronavirus.  

Effects of Plant-Derived Polysaccharides on Murine Cytomegalovirus and Encephalomyocarditis Virus Infections in Mice

1995 ◽  
Vol 6 (6) ◽  
pp. 385-390 ◽  
Author(s):  
D. F. Smee ◽  
A. J. Verbiscar
Keyword(s):  
Body Weight ◽  
Antiviral Activity ◽  
Mouse Models ◽  
Encephalomyocarditis Virus ◽  
Murine Cytomegalovirus ◽  
Virus Infections ◽  
Virus Inoculation ◽  
Antiviral Effects ◽  
Sterculia Urens

Polysaccharides from three plant species, Astragalus brachycentrus (AV222), Astragalus echidnaeformis (AV224) and Sterculia urens (AV223), which are devoid of in vitro antiviral activity, were evaluated in mouse models of murine cytomegalovirus and encephalomyocarditis virus infections. AV223 and AV224 were very potent agents, protecting mice from mortality at intraperitoneal doses between 3.2 and 100 mgkg−1 day−1 treatments. Treatment with compounds needed to be started one day prior to virus inoculation for maximum protective benefit. Treatments starting after virus inoculation were ineffective. No detectable toxicity was apparent in mice treated with up to 100 mg of each polysaccharide per kg of body weight. Interferon was not detected in mouse sera from polysaccharide-treated mice, suggesting a different mode of immuno-enhancement may be responsible for the antiviral effects observed.

scholarly journals In Vitro Inhibition of Zika Virus Replication with Amantadine and Rimantadine Hydrochlorides

2021 ◽  
Author(s):  
Jorge L. Arias-Arias ◽  
Francisco Vega-Aguilar ◽  
Dihalá Picado-Soto ◽  
Eugenia Corrales-Aguilar ◽  
Gilbert D. Loría
Keyword(s):  
Antiviral Activity ◽  
Zika Virus ◽  
Influenza A ◽  
High Selectivity ◽  
Yellow Fever Virus ◽  
Human Infection ◽  
Virus Infections ◽  
Drug Concentrations ◽  
Dose Dependent

Zika virus (ZIKV) is a mosquito-born flavivirus which human infection became relevant dur-ing recent outbreaks in Latin America, due to its unrecognized association with fetal neurologi-cal disorders. Currently there are no approved effective antivirals or vaccines for treatment or prevention of ZIKV infections. Amantadine and rimantadine are approved antivirals used against susceptible influenza A virus infections, that have been shown to have antiviral activity against other viruses, such as dengue virus (DENV). Here, we report the in vitro effectiveness of both amantadine and rimantadine hydrochlorides against ZIKV replication, resulting in a dose-dependent reduction in viral titers of a ZIKV clinical isolate and two different ZIKV refer-ence strains. Additionally, we demonstrate similar in vitro antiviral activity of these drugs against DENV-1 and yellow fever virus (YFV), although at higher drug concentrations for the later. ZIKV replication was inhibited at drug concentrations well below cytotoxic levels of both compounds, as denoted by the high selectivity indexes obtained with the tested strains. Further work is absolutely needed to determine a potential clinical use of these antivirals against ZIKV infections, but our results suggest the existence of a highly conserved mechanism across fla-vivirus, susceptible to be blocked by modified more specific adamantane compounds.

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