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[2 Duckets]

Hypericum perforatum and Its Ingredients Hypericin and Pseudohypericin Demonstrate an Antiviral Activity against SARS-CoV-2

Fakry F Mohamed 1 2, Darisuren Anhlan 1, Michael Schöfbänker 1, André Schreiber 1, Nica Classen 3, Andreas Hensel 3, Georg Hempel 4, Wolfgang Scholz 5, Joachim Kühn 6, Eike R Hrincius 1, Stephan Ludwig 1

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• PMID: 35631357
•  
• PMCID: PMC9146521
•  
• DOI: 10.3390/ph15050530

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Abstract

For almost two years, the COVID-19 pandemic has constituted a major challenge to human health, particularly due to the lack of efficient antivirals to be used against the virus during routine treatment interventions. Multiple treatment options have been investigated for their potential inhibitory effect on SARS-CoV-2. Natural products, such as plant extracts, may be a promising option, as they have shown an antiviral activity against other viruses in the past. Here, a quantified extract of Hypericum perforatum was tested and found to possess a potent antiviral activity against SARS-CoV-2. The antiviral potency of the extract could be attributed to the naphtodianthrones hypericin and pseudohypericin, in contrast to other tested ingredients of the plant material, which did not show any antiviral activity. Hypericum perforatum and its main active ingredient hypericin were also effective against different SARS-CoV-2 variants (Alpha, Beta, Delta, and Omicron). Concerning its mechanism of action, evidence was obtained that Hypericum perforatum and hypericin may hold a direct virus-blocking effect against SARS-CoV-2 virus particles. Taken together, the presented data clearly emphasize the promising antiviral activity of Hypericum perforatum and its active ingredients against SARS-CoV-2 infections.

 

[2 Duckets]

Identification of Hypericin as a Candidate Repurposed Therapeutic Agent for COVID-19 and Its Potential Anti-SARS-CoV-2 Activity

Aline da Rocha Matos 1, Braulia Costa Caetano 1, João Luiz de Almeida Filho 2, Jéssica Santa Cruz de Carvalho Martins 1, Michele Gabrielle Pacheco de Oliveira 1, Thiago das Chagas Sousa 1, Marco Aurélio Pereira Horta 3, Marilda Mendonça Siqueira 1, Jorge Hernandez Fernandez 2

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• PMID: 35222340
•  
• PMCID: PMC8866965
•  
• DOI: 10.3389/fmicb.2022.828984

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Abstract

The COVID-19 pandemic has had an unprecedented impact on the global economy and public health. Its etiologic agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmissible, pathogenic and has a rapid global spread. Currently, the increase in the number of new confirmed cases has been slowed down due to the increase of vaccination in some regions of the world. Still, the rise of new variants has influenced the detection of additional waves of rising cases that some countries have experienced. Since the virus replication cycle is composed of many distinct stages, some viral proteins related to them, as the main-protease (Mpro) and RNA dependent RNA polymerase (RdRp), constitute individual potential antiviral targets. In this study, we challenged the mentioned enzymes against compounds pre-approved by health regulatory agencies in a virtual screening and later in Molecular Mechanics/Poisson-Bolzmann Surface Area (MM/PBSA) analysis. Our results showed that, among the identified potential drugs with anti-SARS-CoV-2 properties, Hypericin, an important component of the Hypericum perforatum that presents antiviral and antitumoral properties, binds with high affinity to viral Mpro and RdRp. Furthermore, we evaluated the activity of Hypericin anti-SARS-CoV-2 replication in an in vitro model of Vero-E6 infected cells. Therefore, we show that Hypericin inhibited viral replication in a dose dependent manner. Moreover, the cytotoxicity of the compound, in cultured cells, was evaluated, but no significant activity was found. Thus, the results observed in this study indicate that Hypericin is an excellent candidate for repurposing for the treatment of COVID-19, with possible inhibition of two important phases of virus maturation.

 

[Hip]

First of all, these are in vitro studies, which do not prove the substance works in vivo.

 

Secondly, the antiviral effects of hypericin increase 100 fold when exposed to light, as it generates highly reactive singlet oxygen in the presence of light. So in vitro experiments conducted under light may give a falsely high antiviral effect which cannot be obtained in the body, since light does not enter deep into the body.

[2 Duckets]

"but a partial effect is also observed in dark conditions, suggesting multiple mechanisms of action for this drug"



The Interaction of Hypericin with SARS-CoV-2 Reveals a Multimodal Antiviral Activity
Pietro Delcanale et al. ACS Appl Mater Interfaces. 2022.
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Abstract
Hypericin is a photosensitizing drug that is active against membrane-enveloped viruses and therefore constitutes a promising candidate for the treatment of SARS-CoV-2 infections. The antiviral efficacy of hypericin is largely determined by its affinity toward viral components and by the number of active molecules loaded on single viruses. Here we use an experimental approach to follow the interaction of hypericin with SARS-CoV-2, and we evaluate its antiviral efficacy, both in the dark and upon photoactivation. Binding to viral particles is directly visualized with fluorescence microscopy, and a strong affinity for the viral particles, most likely for the viral envelope, is measured spectroscopically. The loading of a maximum of approximately 30 molecules per viral particle is estimated, despite with marked heterogeneity among particles. Because of this interaction, nanomolar concentrations of photoactivated hypericin substantially reduce virus infectivity on Vero E6 cells, but a partial effect is also observed in dark conditions, suggesting multiple mechanisms of action for this drug.

Edited by 2 Duckets, 21 October 2022 - 09:15 PM.

[Hip]

"but a partial effect is also observed in dark conditions, suggesting multiple mechanisms of action for this drug"

 

Even with this partial effect in the dark, it's still an in vitro study, and almost all of those in vitro studies do not pan out in vivo.

 

This is because in in vitro studies, they tend to use very high concentrations of the antiviral substance, when they test its antiviral effects in a cell line. When you use super high concentrations, you can often find antiviral effects. But in the body, using the maximum safe dose of the substance, you cannot achieve blood concentrations of the substance anywhere near that used in the the in vitro study.

 

There have been numerous in vitro study finding antiviral substances which are effective in vitro. But pretty much none of those have panned out in vivo, unfortunately.

 

 

 

In the case of the study you posted, they noticed some in vitro antiviral effects at a hypericin concentration of 100 μM. (The unit of μM is a measure of concentration).

 

Well, a pharmacokinetic study found that when you take St John's wort orally, it results in a blood concentration of hypericin at just 3.14 ng/ml = 0.0062 μM.

 

So sadly, the blood concentration achieved is 100 / 0.0062 = 16,000 times lower than the blood concentration used in vitro. 

 

This means there is no hope of hypericin working in vivo.

 

 

 

Often these antiviral studies are not conducted to prove that a substance can have clinical efficacy, but to identify molecules that have antiviral effects. Then pharma companies can use that substance as a lead compound, and make modifications to the compound to make it more effective. 

[Rocket]

Just take methylene blue