Image: Computer Simulation of SARS-CoV-2. Reprinted with kind permission of Janet Iwasa of http://animationlab.utah.edu/cova
Update September 2024
COVID-19 Treatment Strategies
- As of 2023, a few small-molecule antiviral drugs (nirmatrelvir-ritonavir, remdesivir, and molnupiravir) and 11 monoclonal antibodies have been marketed for the treatment of COVID-19, mostly requiring administration within 10 days of symptom onset.
- Hospitalized patients with severe or critical COVID-19 may benefit from treatment with previously approved immunomodulatory drugs, including glucocorticoids such as dexamethasone, cytokine antagonists such as Genentech’s tocilizumab, and Janus kinase inhibitors such as Lilly’s baricitinib.
- Repurposing RNA polymerase nucleotide drugs, such as Gilead’s remdesivir and Merck’s molnupiravir, to inhibit viral RNA synthesis should have a relatively high probability of success, but it remains a trial-and-error endeavour to identify nucleotide/nucleoside analogs that escape the SARS-CoV-2 proofreading mechanism.
- Repurposing DNA polymerase inhibitors, such as Gilead’s tenofovir, to inhibit the RNA synthesis of SARS-CoV-2 is likely to fail due to their different mechanisms of action.
- HIV protease inhibitors, such as lopinavir, should not be repurposed for SARS-CoV-2 treatment due to the lack of similarity between the drug-binding pockets in HIV and SARS-CoV-2 proteases.
- Except for nucleoside/nucleotide inhibitors such as tenofovir, ribavirin, and lamivudine, other virus-targeted inhibitors have not been approved by the FDA to treat more than one infectious disease. They are not good repurposing candidates because their chemical structures are often designed to target a particular drug-binding pocket with high selectivity, and thus they are unlikely to have a similar level of potency against an unrelated target.
- Cationic amphiphilic drugs (such as hydroxychloroquine, azithromycin, and amiodarone) that induce phospholipidosis should not be repurposed, because cellular phospholipidosis is often misinterpreted as antiviral efficacy.
- A new one-step immunoassays has been developed for rapid and sensitive detection of SARS-CoV-2 by using a single-chain variable fragment (scFv) fused to alkaline phosphatase (AP) or NanoLuc (NLuc) luciferase. First, a high-affinity scFv antibody specific to the SARS-CoV-2 nucleocapsid (N) protein was screened from hybridoma cells-derived and phage-displayed library. Next, prokaryotic expression of the scFv-AP and scFv-NLuc fusion proteins were induced, leading to excellent antibody binding properties and enzyme catalytic activities.
- Upregulation of interleukin-6 (IL-6) has been associated with worse prognosis in COVID-19 patients. Janssen conducted a phase 2 randomized control trial to evaluate the efficacy and safety of free IL-6 sequestration by the monoclonal antibody sirukumab in severe and critical COVID-19 patients. In critical COVID-19 patients who received sirukumab, there was no statistically significant difference in time to sustained clinical improvement versus placebo despite objective sequestration of circulating IL-6, questioning IL-6 as a key therapeutic target in COVID-19.
From Dec. 1, 2021
The CDC confirmed today the first case of the Omicron variant, which is officially known as B1.1.529, in the United States. The most concerning aspect of this new variant is the number of mutations associated with it. Viruses are not living organisms; they require a host to continue or survive. The more hosts that viruses can find, the more likely they are to mutate further and potentially become more harmful to the hosts. Viruses cannot replicate on their own. Instead they capture or “hijack” the reproductive mechanism in the host cell, redirect it to copy the genetic code of the virus, and seal it in a packet called a capsid. In a single human being, there can be a billion or even a trillion copies of the SARS-CoV-2 virus. Most of the time, these mutations or mistakes involve different amino acid sequences that may give rise to different proteins but do not enhance the ability of the virus to infect or replicate any better than the original copy. Occasionally, a mutation will increase infectivity and may, or may not, code for a new protein that the immune system fails to recognize.
The spike protein on SARS-CoV-2 interacts specifically with the ACE2 receptor, which is found on the surface of our cells mainly in the GI tract, the respiratory tract, and our vasculature. When the new viral particles are created, they may have slightly different proteins either inside or outside the viral particle. Of particular interest, the mutation may exist on the outer tip of the spike protein, which is called the receptor binding domain (RBD). Our immune system recognizes the SARS-CoV-2 based on the RBD. Thus any mutation that changes the proteins in areas that make it easier for the virus to bind to our cells’ receptors or evade detection by the immune system will be advantageous to virus survival.
Let’s compare Omicron to two prior variants: Alpha and Delta. As to the virus particle itself, Alpha had 23 mutations, Delta had 17 mutations, and Omicron has 50 mutations. As to the spike protein, Alpha had 9 mutations, Delta had 7 mutations, and Omicron has 32 mutations. As to the RBD, Alpha had 1 mutation, Delta had 2 mutations, and Omicron has 10 mutations. The number and variety of mutations associated with the Omicron variant deserves serious concern.
Variants
|
|
Alpha |
Delta |
Omicron |
|
Virus
|
23 mutations |
17 mutations |
50 mutations |
| Spike |
9 mutations |
7 mutations |
32 mutations
|
| RBD |
1 mutation |
2 mutations |
10 mutations
|
Scientists are now focused on three questions: (1) what is the transmissibility of the Omicron variant?, (2) how well does it evade our current COVID-19 vaccines?, and (3) is there a change in the virulence (the variant is more deadly)?
From July 24, 2021
- The Delta variant (B.1.617.2) has proven to be more contagious than the original SARS-CoV-2 (R0 = 3.5–4.5 vs R0 ~ 2.5) perhaps through better binding or better evasion of the immune system. (The spike protein of SARS-CoV-2 is coated with sugar molecules, or glycans, that help it evade the immune system.) The REACT-1 round 12 report (Imperial College London) found the Delta variant prevalence in those aged 5–49 was 2.5 times higher at 0.20% (0.16%, 0.26%) compared with those aged 50 years and above at 0.08% (0.06%, 0.11%). While people over age 50 may have higher vaccination rates, the Delta variant may pose a higher risk of infection for younger-aged individuals. As to hospitalization, The Lancet published correspondence (June 26, 2021) on a study in Scotland that the Delta variant had a 1.85 times higher risk of getting the person infected admitted to the hospital with severe COVID-19 [hazard ratio 1.85 (95% CI 1.39–2.47)]. The Scottish study used Reverse Transcription Polymerase Chain Reaction (RT-PCR) tests and a Cox regression analysis, which adjusts for age, sex, economic status/deprivation, temporal trend, and comorbidities.
- As of July 2021, the Pfizer-BioNTech vaccine was shown to be effective against the Delta variant symptomatic infection at 88% (UK study), 87% (Canadian study), 64% (Israeli study), 79% (Scottish study), and effective against the Delta variant resulting in hospitalization at 96% (UK study) and 98% (Israeli study). The data for the Moderna vaccine are more limited and show the vaccine is 72% effective against symptomatic infection and 96% effective against hospitalization for the Delta variant after just the first dose of the two-dose vaccine. The Oxford-Astrazeneca vaccine was found to be effective against the Delta variant at 60% (UK study), 67% (Canadian study for single dose), 60% (Scottish study) for symptomatic infection and 93% (UK study), 88% (Canadian study) effective against Delta variant hospitalization. For the J&J vaccine, real-world evidence on effectiveness against the Delta variant is not yet available; however, J&J’s internal lab study showed it was highly effective against the South African variant, which was most prevalent at the time, and that the antibody response to the Delta variant is even better: a very good antibody response to the Delta variant based on lab testing.
From May 27, 2021
For early-onset COVID-19 cases (positive COVID-19 test and at-risk for progression of the disease but not experiencing symptoms requiring hospital-ization): “The FDA has halted the distribution of Lilly’s combination of bamlanivimab and etesevimab in Arizona, California, Florida, Indiana, Oregon and Washington––all states where coronavirus variants from Brazil and South Africa account for more than 10% of those with the disease. The antibody combo had previously been paused in Illinois and Massachusetts.
Providers in those states should use Regeneron’s antibody treatment of casirivimab and imdevimab, as per the FDA. Lab studies have shown that option is more effective against the Brazilian (P.1) and South African (B.1.351) strains, according to the agency.” [https://www.fiercepharma.com/pharma/fda-halts-use-lilly-covid-19-antibody-treatment-6-states-where-variants-are-prevalent]
Timing is important: MABS are very good at stopping the virus outside the cells. Once the SARS-CoV-2 has infected the cells, antibodies are not able to neutralize the virus. The patient then needs cytotoxic T-cells.
Two randomized clinical trials of Vitamin D, one from India (SHADE study) and one from Spain (calcifediol study), have shown that Vitamin D supplementation definitely benefitted patients with COVID-19. Emerging evidence shows Vitamin D combined with either or both Vitamin K2 and Magnesium potentiates the benefits of Vitamin D. Source for K2 synergy: https://pubmed.ncbi.nlm.nih.gov/29138634/
QUERCETIN in combination with vitamins C and D, may exert a synergistic antiviral action. Source: https://journals.sagepub.com/doi/full/10.1177/1934578X20976293
N-ACETYL-CYSTEINE (NAC) (600 mg) has known antiviral and liver protective properties. One argument for use with COVID-19 is https://pubmed.ncbi.nlm.nih.gov/32780893/ and another https://pubmed.ncbi.nlm.nih.gov/24968347/ and https://pubmed.ncbi.nlm.nih.gov/9230243/
SLEEP (7 – 9 hours): antibody and immune response after (flu) vaccination is improved if the patient has had a good night’s sleep, particularly the hours of sleep before midnight (slow wave sleep). Optimal T-cell production for disease prevention also requires optimal sleep. Melatonin may help patients get to sleep and has anti-viral properties. https://pubmed.ncbi.nlm.nih.gov/32347747/ https://pubmed.ncbi.nlm.nih.gov/32768490/
At the early stages of COVID-19 infection, the innate immune system is responsible for attacking the virus (primarily using monocytes & natural killer cells) through production of Interferon (IFN). SARS-CoV-2 delays the body’s IFN response. Patients with severe disease had less type I IFN activity in their blood compared to patients with mild to moderate disease. (The innate immune system diminishes with aging.) Any method to enhance the innate immune response in the early course of the disease could limit progression of COVID-19. Sauna baths, hot water baths, and other sources of human hyperthermia can induce a tenfold increase IFN-gamma synthesis. https://pubmed.ncbi.nlm.nih.gov/3132509/ These results suggest that raising the core body temperature akin to a mild fever may stimulate the innate immune system (particularly if followed by a cold shower or rapid cooling) and thereby attenuate COVID-19.
From APRIL 2020
“To be clear, SARS-CoV-2 is not the flu. It causes a disease with different symptoms, spreads and kills more readily, and belongs to a completely different family of viruses. This family, the coronaviruses, includes just six other members that infect humans. Four of them—OC43, HKU1, NL63, and 229E—have been gently annoying humans for more than a century, causing a third of common colds. The other two—MERS and SARS (or “SARS-classic,” as some virologists have started calling it)—both cause far more severe disease. Why was this seventh coronavirus the one to go pandemic? Suddenly, what we do know about coronaviruses becomes a matter of international concern.” Why the Coronavirus Has Been So Successful, The Atlantic
This article was inspired by the work of Jon Barron shown here: https://www.jonbarron.org/colds-flus-infectious-diseases/using-anti-pathogens. To combat the coronavirus, I have stocked my medicine cabinet with the following anti-viral pathogen natural products. In addition to providing the names and doses of the products, after each one, I provide the ten most recent citations from PubMed.gov pertaining to that substance and viruses.
- AHCC (Active Hexose-Correlated Compound) – 500 mg, taken on an empty stomach up to four capsules per day at outset of symptoms
- Olive Leaf Extract (Olea europaea) (standardized to minimum 20% oleuropein) – 500 mg, taken with food once or twice per day.
- Oil of Oregano (Origanum vulgare) (leaf) (10:1 extract) – 150 mg, taken up to four gelcaps per day with water
- Star Anise Oil – 1 fluid oz, blended and diluted with extra virgin olive oil or extra virgin coconut oil
- Minced Garlic — 1 tbsp added to main meal
AHCC (Active Hexose-Correlated Compound)
“Mushrooms have been used for various health conditions for many years by traditional medicines practiced in different regions of the world although the exact effects of mushroom extracts on the immune system are not fully understood. AHCC® is a standardized extract of cultured shiitake or Lentinula edodes mycelia (ECLM) which contains a mixture of nutrients including oligosaccharides, amino acids, and minerals obtained through liquid culture. AHCC® is reported to modulate the numbers and functions of immune cells including natural killer (NK) and T cells which play important roles in host defense, suggesting the possible implication of its supplementation in defending the host against infections and malignancies via modulating the immune system. Here, we review in vivo and in vitro effects of AHCC® on NK and T cells of humans and animals in health and disease, providing a platform for the better understanding of immune-mediated mechanisms and clinical implications of AHCC®.” Shin MS, Park HJ, Maeda T, Nishioka H, Fujii H, Kang I. The Effects of AHCC®, a Standardized Extract of Cultured Lentinura edodes Mycelia, on Natural Killer and T Cells in Health and Disease: Reviews on Human and Animal Studies. J Immunol Res. 2019;2019:3758576. Published 2019 Dec 20. doi:10.1155/2019/3758576 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942843/
Possible therapeutic role of a highly standardized mixture of active compounds derived from cultured Lentinula edodes mycelia (AHCC) in patients infected with 2019 novel coronavirus.
Di Pierro F, et al. Minerva Gastroenterol Dietol 2020. PMID 32162896
The outbreak of SARS-CoV-2 disease (COVID-19) is currently, March 2020, affecting more than 100000 people worldwide and, according to the WHO (World Health Organization), a pandemic is shortly expected. The virus infects the lower respiratory tract and causes severe pneumonia and mortality in approximately 10% and 3-5%, respectively, of cases, mainly among the elderly and/or people affected by other diseases. AHCC is an α-glucan-based standardized mushroom extract that has been extensively investigated as an immunostimulant both in animals and/or in humans affected by West Nile virus, influenza virus, avian influenza virus, hepatitis C virus, papillomavirus, herpes virus, hepatitis B virus and HIV by promoting a regulated and protective immune response. Although the efficacy of AHCC has not yet been specifically evaluated with respect to SARS-CoV-2 disease, its action in promoting a protective response to a wide range of viral infections, and the current absence of effective vaccines, could support its use in the prevention of diseases provoked by human pathogenic coronavirus, including COVID-19.
Ito T, et al. Nutr Cancer 2014 – Clinical Trial. PMID 24611562
The objective of this study was to evaluate the safety and effectiveness of a mushroom product, active hexose correlated compound (AHCC), on chemotherapy-induced adverse effects and quality of life (QOL) in patients with cancer. Twenty-four patients with cancer received their first cycle of chemotherapy without AHCC and then received their second cycle with AHCC. …
Roman BE, et al. Nutr Res 2013 – Clinical Trial. PMID 23351405
In this study, we hypothesized that AHCC will also improve the immune responses of healthy individuals to influenza vaccine. …Immediately post-vaccination, the AHCC group began supplementation with AHCC (3 g/d). Flow cytometric analysis of lymphocyte subpopulations revealed that AHCC supplementation increased NKT cells (P < .1), and CD8 T cells (P < .05) post-vaccination compared to controls. …
Nogusa S, et al. Nutr Res 2009. PMID 19285605
We hypothesized that AHCC supplementation would influence the immune response to influenza infection in a dose-dependent manner. …In conclusion, these data suggest that the effects of AHCC on the immune response to influenza infection are dose dependent and that low-dose AHCC supplementation improves the response to influenza infection despite no effect on total NK cell cytotoxicity….
Wang S, et al. J Nutr 2009. PMID 19141700 Free PMC article.
AHCC administration in aged mice attenuated viremia levels but led to no difference in mortality rate. Overall, our data suggests that AHCC enhances protective host immune responses against WNV infection in young and aged mice. Dietary supplementation with AHCC may be potentially immunotherapeutic for WNV-susceptible populations….
Momiyama K, et al. Cancer Chemother Pharmacol 2009. PMID 19011857
CONCLUSIONS: The percentage of Th2 cells increased in LC patients with aHCC as the efficacy of intra-arterial combination chemotherapy decreased. These results indicated that intra-arterial chemotherapy might be not useful for patients with aHCC, because it induces Th2 dominant host immunity….
Th1/Th2 balance: an important indicator of efficacy for intra-arterial chemotherapy
Nagai H, et al. Cancer Chemother Pharmacol 2008. PMID 18259753
The aim of this study was to assess the influence of intra-arterial combination chemotherapy on the Th1/Th2 balance in LC patients with aHCC. …RESULTS: Thirteen of the 21 aHCC patients (group R) showed an objective response, but the other 8 patients (group N) showed no response. …
Ritz BW, et al. J Nutr 2006. PMID 17056815
However, the effects of AHCC on the response to viral infections have not been studied. In this study, young C57BL/6 mice were supplemented with 1 g AHCC/(kg body weight x d) for 1 wk prior to and throughout infection with influenza A (H1N1, PR8). …These data suggest that AHCC supplementation boosts NK activity, improves survival, and reduces the severity of influenza infection in young mice. …
OLIVE LEAF EXTRACT
“The olive tree (Olea europaea) is native to the Mediterranean region. Olive leaf extract has a long history of use against illnesses in which microorganisms play a major role. In more recent years, studies of olive leaf extracts (containing oleuropein, calcium elenolate, and/or hydroxytyrosol) were effective in eliminating a very broad range of organisms, including bacteria, viruses, parasites, yeast, mold, and fungi., In addition, Olive leaf has demonstrated antiviral activity against both HIV infection and replication, primarily by blocking the entry of the virus into host cells in the body’s immune system.
Studies have also shown that oleuropein exhibits a significant antiviral activity against respiratory syncytial virus and para-influenza type 3 virus. In addition, it has been found to be effective against viral hemorrhagic septicemia rhabdovirus, a highly deadly and infectious virus that afflicts over 50 species of both freshwater and marine water fish. There are studies that demonstrate that olive leaf extracts augment the activity of the HIV-RT inhibitor 3TC. In fact, cell-to-cell transmission of HIV was inhibited in a dose-dependent manner, and replication was inhibited in an in vitro experiment. One of the suspected targets for olive leaf extract action is the HIV-1 gp41 (surface glycoprotein subunit), which is responsible for HIV entry into normal cells. In order to establish HIV protein targets of olive leaf extract and its inhibitory action at the molecular level, researchers reported a joint theoretical and experimental effort has been carried out to help achieve this goal.”
Source: Jon Barron, Using Anti-Pathogens
[Comparison of Antiviral Effect of Olive Leaf Extract and Propolis with Acyclovir on Herpes Simplex Virus Type 1].
Altındiş M, et al. Mikrobiyol Bul 2020. PMID 32050880 Turkish. Free article.
In this in vitro study, olive leaf extract (OLE) and propolis alone or in combination with acyclovir were investigated for their antiviral efficacy in HSV-1.Toxic doses of OLE, propolis, and dimethyl sulfoxide, propolis diluent, for Hep-2 (ATCC, CCL-23) cells were determined by conventional cell culture. Using “endpoint” method, the viral dose infecting half of the cell culture (TCID50) was calculated, and viral quantity was determined with Spearman-Karber method. …
(Oleaceae) is rich in oleuropein (OL), dimethyl-OL, and ligstroside secoiridoids, and their hydrolysis derivatives are mostly OL-aglycone, oleocanthal (OLE), oleacein (OLA), elenolate, oleoside-11-methyl ester, elenoic acid, hydroxytyrosol (HTy), and tyrosol (Ty). These compounds have proved their efficacy in the management of diabetes, cardiovascular and neurodegenerative disorders, cancer, and viral and microbial infections. …
Pleško S, et al. Acta Chim Slov 2015. PMID 26454589
The Zaire Ebola viral protein VP24 selectively inhibits nuclear import of STAT1 and as such blocks interferon-induced antiviral responses vital for cell’s emergency. …Our research shows that 1,2,3,6-tetragalloyl glucose, epigallocatechin gallate, chlorogenic acic, oleuropein and miquelianin represent promising leads for further studies….
Zhao G, et al. J Ethnopharmacol 2009. PMID 19580857
AIM OF THE STUDY: The present study was undertaken to evaluate the effect of oleuropein (Ole) derived from the flowers of JOG on hepatitis B virus (HBV) replication in HepG2 2.2.15 cell line in vitro and duck hepatitis B virus (DHBV) replication in ducklings in vivo. …
Menendez JA, et al. BMC Cancer 2008. PMID 19094209 Free PMC article.
RESULTS: Among the fractions mainly containing the single phenols hydroxytyrosol and tyrosol, the polyphenol acid elenolic acid, the lignans (+)-pinoresinol and 1-(+)-acetoxypinoresinol, and the secoiridoids deacetoxy oleuropein aglycone, ligstroside aglycone, and oleuropein aglycone, all the major EVOO polyphenols (i.e. secoiridoids and lignans) were found to induce strong tumoricidal effects within a micromolar range by selectively triggering high levels of apoptotic cell death in HER2-overexpressors. …EVOO polyphenols-induced HER2 downregulation occurred regardless the molecular mechanism contributing to HER2 overexpression (i.e. naturally by gene amplification and ectopically driven by a viral promoter). …
Roxas M and Jurenka J. Altern Med Rev 2007 – Review. PMID 17397266 Free article.
., Sambucus nigra, larch arabinogalactan, Astragalus membranaceous, Baptisia tinctoria, Allium sativa, Panax quinquefolium, Eleutherococcus senticosus, Andrographis paniculata, olive leaf extract, and Isatis tinctoria) and nutritional considerations (vitamins A and C, zinc, high lactoferrin whey protein, N-acetylcysteine, and DHEA) that may help in the prevention and treatment of these conditions….
Lee-Huang S, et al. Biochem Biophys Res Commun 2007. PMID 17275783 Free PMC article.
We have identified oleuropein (Ole) and hydroxytyrosol (HT) as a unique class of HIV-1 inhibitors from olive leaf extracts effective against viral fusion and integration. We used molecular docking simulation to study the interactions of Ole and HT with viral targets. We find that Ole and HT bind to the conserved hydrophobic pocket on the surface of the HIV-gp41 fusion domain by hydrogen bonds with Q577 and hydrophobic interactions with I573, G572, and L568 on the gp41 N-terminal heptad repeat peptide N36, interfering with formation of the gp41 fusion-active core. …
Micol V, et al. Antiviral Res 2005. PMID 15869811
A commercial plant extract derived from olive tree leaf (Olea europaea) (LExt) and its major compound, oleuropein (Ole), inhibited the in vitro infectivity of the viral haemorrhagic septicaemia virus (VHSV), a salmonid rhabdovirus. Incubation of virus with LExt or Ole before infection reduced the viral infectivity to 10 and 30%, respectively. Furthermore, LExt drastically decreased VHSV titers and viral protein accumulation (virucidal effect) in a dose dependent manner when added to cell monolayers 36 h post-infection. …
Lee-Huang S, et al. Biochem Biophys Res Commun 2003. PMID 12878215
We investigated the antiviral activity of olive leaf extract (OLE) preparations standardized by liquid chromatography-coupled mass spectrometry (LC-MS) against HIV-1 infection and replication. …To identify viral and host targets for OLE, we characterized gene expression profiles associated with HIV-1 infection and OLE treatment using cDNA microarrays. …
Ma SC, et al. Chem Pharm Bull (Tokyo) 2001. PMID 11724241 Free article.
Six secoiridoid glucosides, lucidumoside C (1), oleoside dimethylester (2), neonuezhenide (3), oleuropein (4), ligustroside (5) and lucidumoside A (6), isolated from the fruits of Ligustrum lucidum (Oleaceae), were examined in vitro for their activities against four strains of pathogenic viruses, namely herpes simplex type I virus (HSV-1), influenza type A virus (Flu A), respiratory syncytial virus (RSV) and parainfluenza type 3 virus (Para 3). …Oleuropein, however, showed significant antiviral activities against RSV and Para 3 with IC50 value of 23.4 and 11.7 microg/ml, respectively. …
Konlee M. Posit Health News 1998. PMID 11366542
For quadruple therapy, a reverse transcriptase inhibitor such as olive leaf extract or Epivir (3TC) could be added. In one case, a female, taking no HIV drugs, used an elderberry extract, called Sambucol, with olive leaf extract and experienced a viral load drop from 17,000 to 4,000. …
Oil of Oregano
Antifungal Activity of Selected Natural Preservatives against Aspergillus westerdijkiae and Penicillium verrucosum and the Interactions of These Preservatives with Food Components
Schlösser I and Prange A. J Food Prot 2019. PMID 31538828
The present study examined the influence of primary food components on the antifungal activity of the essential oil of Origanum vulgare, carvacrol, thymol, eugenol, and trans-cinnamaldehyde against Penicillium verrucosum and Aspergillus westerdijkiae. …The presence of oil had the strongest influence. At a concentration of 1% oil, the antifungal activity decreased significantly, and at 10% oil, almost no inhibition was observed. …
Man A, et al. Pathogens 2019. PMID 30696051 Free PMC article.
The most active oils were oregano, thyme, lemon and lavender, while the least active were frankincense and myrtle. Oregano oil presented up to 64 times lower MICs/MBCs than ethylic alcohol, if considered as standard, on all bacteria. …Aqueous extracts of oregano or thyme oil with good antibacterial activity could also be used in selected cases….
Scalas D, et al. BMC Complement Altern Med 2018. PMID 29724221 Free PMC article.
Since the essential oils (EOs) are considered as a potential rich source of bioactive antimicrobial compounds, we evaluated the antifungal activity of Origanum vulgare (oregano), Pinus sylvestris (pine), and Thymus vulgaris (thyme red) EOs, and their components (α-pinene, carvacrol, thymol) compared with fluconazole, itraconazole, and voriconazole, against C.neoformans clinical strains. …Time-kill assays confirmed the synergistic effects of itraconazole and oregano or thyme EO against azole susceptible C.neoformans. …
Lionis C. Hell J Nucl Med 2015. PMID 26665228
However, it was the first attempt in Europe when a double blind randomized controlled trial examined the effectiveness of an essential-oil extract of three Cretan aromatic plants (Origanum Dictamnus, Coridothymus Capitatus, Salvia Friticosa) designed and implemented in rural Crete on patients with upper respiratory tract infection. …In conclusion, the two first studies on the Cretan medicinal and aromatic plants support the potentialities of the use of Ethno botanical methodology to move the needle of innovation on viral infections and lipids metabolism….
Sánchez G and Aznar R. Food Environ Virol 2015. PMID 25636749
(zataria) and Origanum vulgare (oregano) EOs on hepatitis A virus (HAV) and the effect of thymol, an active compound of Thymus vulgaris and oregano, on norovirus surrogates, feline calicivirus (FCV) and murine norovirus (MNV), and HAV. …Treatment with oregano and zataria EOs resulted in slight reductions on HAV infectivity with a maximum reduction of less than 0.5 log TCID(50)/ml at 0.1 % zataria EO. …
Gilling DH, et al. J Appl Microbiol 2014. PMID 24779581 Free article.
AIMS: To investigate the antiviral efficacy of oregano oil and its primary active component, carvacrol, against the nonenveloped murine norovirus (MNV), a human norovirus surrogate. …Under TEM, the capsids enlarged from ≤35 nm in diameter to up to 75 nm following treatment with oregano oil and up to 800 nm with carvacrol; with greater expansion, capsid disintegration could be observed. …
Pilau MR, et al. Braz J Microbiol 2011. PMID 24031796 Free PMC article.
Thus, Mexican oregano oil and its main component, carvacrol, are able to inhibit different human and animal viruses in vitro. Specifically, the antiviral effects of Mexican oregano oil on ACVR-HHV-1 and HRSV and of carvacrol on RV justify more detailed studies….
Preuss HG, et al. Mol Cell Biochem 2005. PMID 16010969
New, safe antimicrobial agents are needed to prevent and overcome severe bacterial, viral, and fungal infections. Based on our previous experience and that of others, we postulated that herbal essential oils, such as those of origanum, and monolaurin offer such possibilities. We examined in vitro the cidal and/or static effects of oil of origanum, several other essential oils, and monolaurin on Staphylococcus aureus, Bacillus anthracis Sterne, Escherichia coli, Klebsiella pneumoniae, Helicobacter pylori, and Mycobacterium terrae. …
Star Anise Oil (Pimpinella Anisum)
“The Chinese star anise plant has a long history as a healing herb — for digestive problems, women’s health, and for treating colds and flu. The Swiss pharmaceutical company, Roche, focused in on the cold and flu benefit and then “subtracted out” all of the “extraneous” biochemicals in the plant until they settled on one component, shikimic acid, that they said was responsible for the star anise plant’s ability to inhibit colds and flu’s. From shikimic acid, they synthesized oseltamivir (for patent purposes), and thus was born Tamiflu. This is a subtractive process. You eliminate everything “extraneous” and get down to one single active ingredient. Of course, there are major problems with this magic bullet approach.”
https://www.jonbarron.org/colds-flus-infectious-diseases/using-anti-pathogens
[Potential antiviral therapeutics for 2019 Novel Coronavirus]
Li H, et al. Zhonghua Jie He He Hu Xi Za Zhi 2020. PMID 32164080 Chinese.
Antiviral drugs commonly used in clinical practice, including neuraminidase inhibitors (oseltamivir, paramivir, zanamivir, etc.), ganciclovir, acyclovir and ribavirin, are invalid for 2019-nCoV and not recommended. …
Screening for antiviral activities of isolated compounds from essential oils
Astani A, et al. Evid Based Complement Alternat Med 2011.
Essential oil of star anise as well as phenylpropanoids and sesquiterpenes, for example, trans-anethole, eugenol, β-eudesmol, farnesol, β-caryophyllene and β-caryophyllene oxide, which are present in many essential oils, were examined for their antiviral activity against herpes simplex virus type 1 (HSV-1) in vitro. Antiviral activity was analyzed by plaque reduction assays and mode of antiviral action was determined by addition of the drugs to uninfected cells, to the virus prior to infection or to herpesvirus-infected cells. Star anise oil reduced viral infectivity by >99%, phenylpropanoids inhibited HSV infectivity by about 60-80% and sesquiterpenes suppressed herpes virus infection by 40-98%. Both, star anise essential oil and all isolated compounds exhibited anti-HSV-1 activity by direct inactivation of free virus particles in viral suspension assays. All tested drugs interacted in a dose-dependent manner with herpesvirus particles, thereby inactivating viral infectivity. Star anise oil, rich in trans-anethole, revealed a high selectivity index of 160 against HSV, whereas among the isolated compounds only β-caryophyllene displayed a high selectivity index of 140. The presence of β-caryophyllene in many essential oils might contribute strongly to their antiviral ability. These results indicate that phenylpropanoids and sesquiterpenes present in essential oils contribute to their antiviral activity against HSV.
Chemical Constituents of Essential Oils Possessing Anti-Influenza A/WS/33 Virus Activity
Choi HJ. Osong Public Health Res Perspect 2018. PMID 30584499 Free PMC article.
The chemical composition detected by GC-MS analysis, differed amongst the 3 most potent anti-viral essential oils (marjoram, clary sage and anise oils) except for linalool, which was detected in all 3 essential oils. CONCLUSION: This study demonstrated anti-influenza activity in 11 essential oils tested, with marjoram, clary sage and anise essential oils being the most effective at reducing visible cytopathic effects of the A/WS/33 virus. …
Efficacy of anise oil, dwarf-pine oil and chamomile oil against thymidine-kinase-positive and thymidine-kinase-negative herpesviruses.
Koch C, et al. J Pharm Pharmacol 2008. PMID 18957177
The effect of anise oil, dwarf-pine oil and chamomile oil against different thymidine-kinase-positive (aciclovir-sensitive) and thymidine-kinase-negative (aciclovir-resistant) herpes simplex virus type 1 (HSV-1) strains was examined. …No significant effect on viral infectivity could be achieved by adding these compounds during the replication phase. These results indicate that anise oil, dwarf-pine oil and chamomile oil affected the virus by interrupting adsorption of herpesviruses and in a different manner than aciclovir, which is effective after attachment inside the infected cells. …
Inhibitory effect of essential oils against herpes simplex virus type 2
Koch C, et al. Phytomedicine 2008. PMID 17976968
In order to determine the mode of the inhibitory effect, essential oils were added at different stages during the viral infection cycle. …These results indicate that essential oils affected HSV-2 mainly before adsorption probably by interacting with the viral envelope. …
Garlic
Garlic for the common cold.
Lissiman E, et al. Cochrane Database Syst Rev 2014 – Review. PMID 25386977 Free PMC article.
Background Garlic is alleged to have antimicrobial and antiviral properties that relieve the common cold, among other beneficial effects. …The trial reported 24 occurrences of the common cold in the garlic intervention group compared with 65 in the placebo group (P value < 0.001), resulting in fewer days of illness in the garlic group compared with the placebo group (111 versus 366). …
Li M, et al. J Food Sci 2017. PMID 28196294
Garlic has a long history to be used for medicine and food purposes. Black garlic, the fermented product of fresh garlic, is considered with better biological activities, such as antioxidant activity, and is developed as an increasingly popular functional food. …The results indicated that fresh garlic polysaccharide exhibited stronger immunomodulatory activities than that of black garlic. …
Ankri S and Mirelman D. Microbes Infect 1999 – Review. PMID 10594976
Allicin, one of the active principles of freshly crushed garlic homogenates, has a variety of antimicrobial activities. Allicin in its pure form was found to exhibit i) antibacterial activity against a wide range of Gram-negative and Gram-positive bacteria, including multidrug-resistant enterotoxicogenic strains of Escherichia coli; ii) antifungal activity, particularly against Candida albicans; iii) antiparasitic activity, including some major human intestinal protozoan parasites such as Entamoeba histolytica and Giardia lamblia; and iv) antiviral activity. …
Gökalp F. J Biochem Mol Toxicol 2018. PMID 30194790
Garlic has been used as a traditional medicine to treat various diseases. Garlic reduces the risk of some diseases. This protective effect is due to the organosulfur compounds of garlic. …The chemical activity and solubility of ajoene and the mainly derived compounds of garlic as theoretical calculations are important for the medical research comparing with the other compounds of the garlic. …
Foroutan-Rad M, et al. J Evid Based Complementary Altern Med 2017 – Review. PMID 26721553 Free PMC article.
The aim of this study is to review the effectiveness, toxicities, and possible mechanisms of pharmaceutical actions of different garlic extracts and organosulfur compounds isolated from garlic against Leishmania spp. in a variety of in vitro, in vivo and clinical trials reports. …In summary, garlic with immunomodulatory effects and apoptosis induction contributes to the treatment of leishmaniasis….
Talib WH. Nutrition 2017. PMID 28935151
OBJECTIVES: Dietary agents play an important role in cancer prevention and therapy because of their low toxicity and the perception that they are not a medicine. The aim of the present study was to investigate the anticancer effect of the administration of garlic and lemon aqueous extracts against breast cancer implanted in mice. …
Garlic (Allium sativum L.) is grown all over the world as seasoning and medicinal vegetable since 3,000 BC. Allicin is the main component of garlic, being attributed to it the most of its biological activities, such as bactericidal, antifungal and antiviral actions. …Mice that consumed garlic responded more effectively to fight against the infection….
Rasool A, et al. Pak J Pharm Sci 2017. PMID 29039335
Aqueous extract of ginger had antiviral activity at 10, 15, 20 and 25% while garlic had activity at 15, 20 and 25%. Histopathological scoring of chorio-allantoic membrane for aqueous extracts (5, 10, 15, 20, 25%) of ginger (0.66±0.57, 1.33±0.57, 1.66±0.57, 2.66±0.57, 3.66±0.57, respectively) and garlic (1.00±0.00, 1.33±0.57, 2.00±0.00, 2.33±0.57, 3.66±0.57, respectively) was concentration dependant. …Overall results revealed that concentration of aqueous extract of ginger (10%), showing antiviral activity against H(9)N(2), was less toxic to vero cells (> 50% cell survival). …
In vitro virucidal effects of Allium sativum (garlic) extract and compounds.
Weber ND, et al. Planta Med 1992. PMID 1470664
Garlic (Allium sativum) has been shown to have antiviral activity, but the compounds responsible have not been identified. Using direct pre-infection incubation assays, we determined the in vitro virucidal effects of fresh garlic extract, its polar fraction, and the following garlic associated compounds: diallyl thiosulfinate (allicin), allyl methyl thiosulfinate, methyl allyl thiosulfinate, ajoene, alliin, deoxyalliin, diallyl disulfide, and diallyl trisulfide. …Lack of reduction in yields of infectious virus indicated undetectable levels of intracellular antiviral activity for either allicin or fresh garlic extract. …
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