Caryophyllene oxide for COVID-19

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COVID-19 Treatment Clinical Evidence

COVID-19 involves the interplay of 400+ viral and host proteins and factors, providing many therapeutic targets. c19early analyzes 6,000+ studies for 210+ treatments—over 17 million hours of research. Only three high-profit early treatments are approved in the US. In reality, many treatments reduce risk, with 25 low-cost treatments approved across 163 countries.

Naso/oropharyngeal treatment Effective Treatment directly to the primary source of initial infection.
Healthy lifestyles Protective Exercise, sunlight, a healthy diet, and good sleep all reduce risk.
Immune support Effective Vitamins A, C, D, and zinc show reduced risk, as with other viruses.
Thermotherapy Effective Methods for increasing internal body temperature, enhancing immune system function.
Systemic agents Effective Many systemic agents reduce risk, and may be required when infection progresses.
High-profit systemic agents Conditional Effective, but with greater access and cost barriers.
Monoclonal antibodies Limited Utility Effective but rarely used—high cost, variant dependence, IV/SC admin.
Acetaminophen Harmful Increased risk of severe outcomes and mortality.
Remdesivir Harmful Increased mortality with longer followup. Increased kidney and liver injury, cardiac disorders.

Caryophyllene oxide may be beneficial for COVID-19 according to the studies below. COVID-19 involves the interplay of 400+ viral and host proteins and factors providing many therapeutic targets. Scientists have proposed 11,000+ potential treatments. c19early.org analyzes 210+ treatments. We have not reviewed caryophyllene oxide in detail.

Studies suggesting benefit with caryophyllene oxide

Chen et al., Broad-spectrum inhibition of SARS-CoV-2 variants by dibutyl phthalate through allosteric disruption of Spike-ACE2 interface, Frontiers in Microbiology, doi:10.3389/fmicb.2025.1610775

Introduction The persistent evolution of SARS-CoV-2 has diminished the efficacy of existing vaccines and antibodies, increasing the risks of reinfection and Long COVID. There is a significant need for the development of convenient, broad-spectrum antiviral agents that target the early stage of viral infection. Traditional Chinese Medicine (TCM) volatile oils, with their diverse components and suitability for nasal delivery, demonstrate potential against respiratory viruses. This study aimed to screen bioactive compounds from TCM volatile oils for their ability to inhibit the interaction between the SARS-CoV-2 spike (S) protein and its host receptor, ACE2. Methods A virtual screening of 47 structurally diverse TCM volatile compounds was performed to identify potential inhibitors of the Spike-ACE2 interaction. The top candidate, dibutyl phthalate (DBP), was further evaluated using in vitro assays including Spike-mediated membrane fusion and pseudovirus infection. Its mechanism was investigated through ELISA, surface plasmon resonance (SPR), ACE2 enzymatic activity assays, molecular docking. To evaluate its broad-spectrum potential, membrane fusion assays were further performed using spike proteins from the wild-type (WT), Delta, and Omicron XBB.1.5 variants. Critical binding residues were identified through molecular docking and subsequently confirmed by site-directed mutagenesis of the Spike receptor-binding domain (RBD). Results Virtual screening identified ten potential inhibitors, with dibutyl phthalate (DBP) showing the strongest activity. DBP effectively inhibited S protein-mediated membrane fusion ( IC 50 = 64.53 μM) and pseudovirus infection ( IC 50 = 73.06 μM) with specificity. SPR analysis confirmed that DBP competitively inhibited the binding between the S trimer and ACE2 (increasing the K D from 8.28 nM to 86.7 nM). Mechanistic studies revealed that DBP disrupts the S-ACE2 interaction by targeting the receptor-binding domain (RBD) without affecting ACE2 enzymatic activity. Furthermore, DBP exhibited broad-spectrum inhibitory activity against membrane fusion mediated by the Delta ( IC 50 = 49.22 μM) and Omicron XBB.1.5 ( IC 50 = 53.70 μM) spike variants. Molecular docking and subsequent site-directed mutagenesis identified Tyr453 and Tyr495 as critical residues for DBP binding and its inhibitory function. ..

Zaher et al., GC/MS Analysis, Cytotoxicity, and Antimicrobial Properties of Six Moroccan Essential Oils Traditionally Used for COVID-19 Prevention, Molecules, doi:10.3390/molecules30214179

The COVID-19 pandemic has reignited interest in traditional medicinal plants as potential therapeutic agents. This study examined the chemical composition, cytotoxicity, and antimicrobial activity of essential oils from six Moroccan medicinal plants, namely, Eucalyptus globulus, Artemisia absinthium, Syzygium aromaticum, Thymus vulgaris, Artemisia alba, and Santolina chamaecyparissus, which are commonly used by the Moroccan population for COVID-19 prevention. The chemical composition of each essential oil was determined using gas chromatography–mass spectrometry (GC–MS) to identify key compounds. Cytotoxicity was evaluated in the Vero E6 cell line, which is frequently used in SARS-CoV-2 research, using the neutral red assay, with oil concentrations ranging from 25 to 100 µg/mL. Antimicrobial activity was tested against standard reference strains, including Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Staphylococcus aureus (ATCC 25923), Candida albicans (ATCC 10231), and Bacillus subtilis (ATCC 6633), using the disc diffusion method. GC–MS analysis revealed significant components such as spathulenol (15%) and caryophyllene oxide (7.67%) in Eucalyptus globulus and eugenol (54.96%) in Syzygium aromaticum. Cytotoxicity assays indicated that higher concentrations of essential oils significantly reduced cell viability, with Thymus vulgaris showing the highest IC50 (8.324 µM) and Artemisia absinthium the lowest (18.49 µM). In terms of antimicrobial activity, Eucalyptus globulus had the strongest effect, with a 20 ± 0.00 mm inhibition zone against Bacillus subtilis, whereas both Syzygium aromaticum and Artemisia herba-alba had a 12.25 ± 0.1 mm inhibition zone against the same strain. These findings suggest that these essential oils have significant therapeutic potential, particularly in combating antimicrobial resistance and exerting cytotoxic effects on viral cell lines. Further research is necessary to explore their mechanisms of action and ensure their safety for therapeutic use.