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A study published in Pathogens attracted the attention of many people.
Pathogens is an international, peer-reviewed, open access journal of pathogens and pathogen-host interactions published monthly online by MDPI.
On November 20, Pathogens shared the results of a study titled, “Highly Specific Sigma Receptor Ligands Exhibit Anti-Viral Properties in SARS-CoV-2 Infected Cells.”
This study focused on the potential treatment and prevention of COVID-19 that aren’t affected by mutations and variants.
Here’s an abstract:
(1) Background: There is a strong need for prevention and treatment strategies for COVID-19 that are not impacted by SARS-CoV-2 mutations emerging in variants of concern. After virus infection, host ER resident sigma receptors form direct interactions with non-structural SARS-CoV-2 proteins present in the replication complex. (2) Methods: In this work, highly specific sigma receptor ligands were investigated for their ability to inhibit both SARS-CoV-2 genome replication and virus induced cellular toxicity. This study found antiviral activity associated with agonism of the sigma-1 receptor (e.g., SA4503), ligation of the sigma-2 receptor (e.g., CM398), and a combination of the two pathways (e.g., AZ66). (3) Results: Intermolecular contacts between these ligands and sigma receptors were identified by structural modeling. (4) Conclusions: Sigma receptor ligands and drugs with off-target sigma receptor binding characteristics were effective at inhibiting SARS-CoV-2 infection in primate and human cells, representing a potential therapeutic avenue for COVID-19 prevention and treatment.
Here are more details of potential coronavirus treatments:
Specific antihistamines with off-target antiviral activity may have repurposed utility for prevention and treatment of COVID-19 because of known safety profiles and widespread availability. Common antihistamines that exhibit off-target antiviral activity include hydroxyzine, azelastine and diphenhydramine . Mechanisms of action for drugs with direct anti-SARS-CoV-2 activity have important clinical implications in terms of dosing and drug interactions. Defining mechanisms that drive antiviral activity against SARS-CoV-2 will provide rationale for drug combinations targeting distinct antiviral pathways . Drug combinations that target separate antiviral pathways are expected to inhibit drug resistant variants resulting from emerging mutations.
Coronaviruses replicate in a modified compartment derived from the endoplasmic reticulum (ER). The sigma receptor-1 is an ER resident chaperone that normally functions to modulate the ER stress response . Coronavirus infection activates pathways to facilitate adaptation of ER stress to virus proliferation. These pathways are thought to hijack the host cell ER stress response to modulate protein translation, ER protein folding capacity and ER-associated degradation. Targeting the ER stress response could elucidate coronavirus protein-host interactions and provide rationale for new therapeutic approaches to prevention and treatment of COVID-19.
Diphenhydramine is Benadryl.
Diphenhydramine is an antihistamine mainly used to treat allergies. It can also be used for insomnia, symptoms of the common cold, tremor in parkinsonism, and nausea. It is used by mouth, injection into a vein, injection into a muscle, or applied to the skin. Maximal effect is typically around two hours after a dose, and effects can last for up to seven hours.
Common side effects include sleepiness, poor coordination and an upset stomach. Its use is not recommended in young children or the elderly. There is no clear risk of harm when used during pregnancy; however, use during breastfeeding is not recommended. It is a first generation H1-antihistamine and ethanolamine and works by blocking certain effects of histamine. Diphenhydramine is also an anticholinergic.
Diphenhydramine was first made by George Rieveschl and came into commercial use in 1946. It is available as a generic medication. It is sold under the trade name Benadryl, among others. In 2017, it was the 241st most commonly prescribed medication in the United States, with more than two million prescriptions.
Can Benadryl help in the treatment?
The antihistamine diphenhydramine, with on-target binding to the Histamine-1 receptor, has known off-target effects at the sigma-1 receptor . Diphenhydramine was recently shown to inhibit SARS-CoV-2 infectivity and the calculated EC50 for SARS-CoV-2 by plaque reduction assay was 17.4 μg/mL (59.6 μM). This drug is safe, well-characterized, and widely available and so highly relevant in the search for COVID therapeutics. We investigated the ability of diphenhydramine to inhibit SARS-CoV-2 induced cytotoxicity and found an EC50 of 122.0 μg/mL (418 μM; Figure 8A,B), about 7 times higher than that found in the plaque reduction assay, similar to our findings with AZ66. We hypothesized that diphenhydramine could be combined with structurally distinct antiviral agents (binding other receptors, not sigma) to reduce its EC50 for antiviral activity against SARS-CoV-2.
In our investigations into sigma-binding ligands, including diphenhydramine, we sought to reduce the EC50 by addition of another safe, and well characterized protein from milk, lactoferrin. The host-iron sequestration protein lactoferrin was reported to exhibit direct antiviral activity against SARS-CoV-2 [28,29], is broadly antimicrobial, and possesses host immunostimulatory properties. We tested combinations of lactoferrin with diphenhydramine to measure effects on reduction of EC50. Co-administration of 400 μg/mL of lactoferrin with diphenhydramine further reduced SARS-CoV-2 induced cytotoxicity and decreased the EC50 by 55.5% to 54.2 μg/mL (185.7 μM; Figure 8C,D). The antiviral enhancement effects of lactoferrin are more apparent at lower, therapeutically relevant concentrations of diphenhydramine (Figure 8E). Inhibition of viral replication was also investigated by qPCR (Figure 8F). Lactoferrin (400 μg/mL) was able to decrease N-protein RNA copies by 28.0% 48 h after infection, compared to DMSO alone controls while 40 μg/mL diphenhydramine alone resulted in 32.2% reduction. When combined, they inhibited 99.97% of N-protein RNA copies, a 3-log reduction that was highly significant. These data demonstrate that combinations of two over-the-counter compounds, with well characterized safety profiles, have synergistic effects on inhibition of SARS-CoV-2.
This research suggests that diphenhydramine and lactoferrin can inhibit the virus.
“When combined, they inhibited 99.97% of N-protein RNA copies, a 3-log reduction that was highly significant.”
The antiviral properties of lactoferrin makes it a great natural supplement that could also be used as an adjunct for COVID-19 and for various other Respiratory Tract Infections (RTIs) according to a team of researchers led by the University of Huddersfield.
Lactoferrin is a protein naturally found in breastmilk, for example in cow milk and human milk, and is also found in fluids in the eye, nose, respiratory tract, intestine, and elsewhere. The benefits are well documented however, it wasn’t known if taking the molecule as a supplement would have the same beneficial value, until now.
The findings of the study, headed by the University’s Dr Hamid Merchant from the University’s Department of Pharmacy is one of the first meta-analyses carried out on multiple independent lactoferrin clinical trials that is now published in an official publication of the European Society for Clinical Nutrition and Metabolism (ESPEN). The study has made evident that the administration of Lactoferrin shows promising efficacy in reducing the risk of RTIs, which is proven to be a key ingredient for our natural defense systems against invading viruses.
— DoubleDoc🇺🇲🕯️🙏⭐🎯 (@SweetBoySammy) November 23, 2021
Used to treat the common cold.
Effective treatment against covid
So all those hospitals not even providing cold medication to treat a cold virus (Corona virus).
Those doctors and hospital administrators better be hanging their heads in shame.
— eLouai (@elouai) November 23, 2021
A lot of people have a histamine reaction to covid. Benadryl is a good anti-histamine.
It's a dirty old drug so I'd prefer the newer ones. They are common in post-covid treatment
— Doc Anarchy, MD | Substack (@DoctorAnarchist) November 23, 2021
— TrialSite News (@TrialsiteN) March 30, 2021
Benedryl highly effective to treat covid19 especially when combined with antivirals like HCQ.https://t.co/9QVg4fSoS3
— PN,MPH, PhD (@PN_1984) November 23, 2021
This isn’t the first time scientists have mentioned antihistamines as a treatment.
What are your thoughts on this?
Observational study, but data shows that Benadryl, yes, 'that Benadryl', is significantly effective in "reducing fatality rate, hospital admissions and ICU admissions" among the infected elderly.
Low cost, minimal side effects, available everywhere. https://t.co/vQlY0rwT8N
— B (@AllISeeIsLegacy) November 23, 2021
Study out of Spain showed success with Antihistamines in nursing homes. Benadryl would make sense.https://t.co/RO4QRhhhpe
— Optimistic realist (@justaguyin_IL) November 23, 2021
https://t.co/R07eoYbUZl I take either a zyrtec or claritin in the am and a benadryl in the pm every day for allergies. Been doing it for several years. No clots, no myocarditis, no GBS. I just sleepy after the benadryl.
— ThirdMonkey (@ThirdMonkey97) November 23, 2021
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