💊 Suitability of Cordycepin as an Ideal Drug-Like Molecule in COVID-19 Management

🧬 Cordycepin: A Unique Molecule That Neutralizes SARS-CoV-2 by Four Mechanisms

Recent research highlights cordycepin as an exceptionally drug-like molecule for several key reasons:

1. Drug-likeness: Cordycepin fully adheres to Lipinski’s Rule of Five, with no violations, indicating excellent potential as an orally active drug.

   
   

2. Bioavailability: With a bioavailability (BA) score of 0.55, cordycepin is considered moderately to well absorbed in the gastrointestinal tract, supporting its therapeutic applicability.

   
   

3. Solubility: Cordycepin is highly water-soluble, with an estimated solubility of 10 mg/mL (or 10 g/L) at physiological temperature (37 °C). This contributes to its absorption efficiency.

   
   

4. Toxicity and Selectivity: In vitro cytotoxicity assays show a CC₅₀ value exceeding 100 μM, suggesting low toxicity and a high safety profile. Its selectivity index (SI > 49.75) far surpasses that of remdesivir (SI > 4.76) and GS-441524 (SI > 6.41). This demonstrates targeted antiviral activity against SARS-CoV-2, with minimal impact on host RNA or cellular processes. Cordycepin is also non-carcinogenic and does not cross the blood-brain barrier.

   
   

🌍 A Natural Remedy in the COVID-19 Pandemic

During the COVID-19 pandemic, global attention turned not only to vaccines and pharmaceuticals but also to natural compounds with potent antiviral effects. Among these, Cordyceps militaris—commonly known as Keeda Jadi mushroom—emerged as a standout remedy. Its primary bioactive compound, cordycepin, is known to neutralize all major variants of SARS-CoV-2 through four powerful mechanisms:

1. RBD Inhibition: Cordycepin binds to the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein. By doing this, it blocks the virus from attaching to ACE2 receptors on human cells, such as those in the lungs, heart, intestines, kidneys, and blood vessels. This significantly reduces the virus’s ability to enter host cells.

   
   

2. Main Protease Inhibition: Cordycepin effectively targets the virus’s main protease (Mpro or 3CLpro). This disrupts the replication cycle, preventing the production of new viral particles.

   
   

3. RdRp Suppression: Cordycepin inhibits the viral RNA-dependent RNA polymerase (RdRp) with an EC₅₀ of just 2.01 μM. This makes it 10.5 times and 7.8 times more effective than remdesivir and GS-441524, respectively, in vitro, in blocking RNA replication.

   
   

4. Adenosine Mimicry: As an adenosine analog, cordycepin interferes with RNA synthesis by being misincorporated into viral RNA strands. This results in premature termination, mutations, or the creation of non-functional RNA fragments. Importantly, human RNA polymerases preferentially incorporate natural adenosine, sparing normal cellular function.

   
   

These four mechanisms act synergistically to halt the spread and progression of COVID-19 inside the body.

🛡️ How Cordyceps militaris Fights COVID-19

A Natural Warrior Against Viral Infections, Inflammation & Immune Dysregulation

1️⃣ Shielding the Body: Cordyceps for COVID-19 Prevention

Cordycepin, the star compound of Cordyceps militaris, is a powerful nucleoside analog with high gastrointestinal absorption and a bioavailability of 0.55. After ingestion, it circulates through the body within 36–48 hours. Once in the bloodstream, it targets the Receptor-Binding Domain (RBD) of the SARS-CoV-2 Spike protein—blocking the virus from attaching to human cells.

➡️ Daily intake of Cordyceps (Keeda Jadi) may act as a viral shield, helping reduce the chances of infection.

2️⃣ Halting Viral Spread: Multi-Target Disruption of SARS-CoV-2

Once infected, Cordycepin quickly works to block the virus from replicating and spreading. It interferes with multiple viral processes:

• ❌ Inhibits viral main protease (Mpro)

• ❌ Suppresses RNA-dependent RNA polymerase (RdRp)

• ❌ Mimics adenosine to create non-functional viral RNA fragments

  
  

📉 Result: Reduced viral load and slower disease progression when taken at early symptom onset.

3️⃣ Fungal Steroids vs. Cytokine Storm: Natural Anti-inflammatory Power

Scientific studies show that five steroid compounds in Cordyceps militaris target 17 inflammatory pathways and 11 critical proteins linked to severe COVID-19 inflammation. Key players, like Beta-sitosterol and Cholest-4-en-3-one, modulate pathways similar to pharmaceutical steroids.

🧬 These natural steroids could help manage cytokine storms, offering a safer alternative to synthetic corticosteroids in inflammatory COVID-19 cases.

4️⃣ Rapid Relief: Whole-Body Anti-inflammatory Effects

Beyond steroids, Cordyceps militaris contains several other inflammation-fighting compounds:

• 🧪 Cordycepin – Modulates ACE2 enzyme and associated pathways

• 🧪 Adenosine – Regulates immune signaling

• 🧪 Exopolysaccharides (EPSF) and phenolic compounds – Combat cellular inflammation

  
  

☕ A single cup of Cordyceps tea can bring noticeable relief within hours, especially for throat and sinus inflammation.

5️⃣ Immunity in Balance: Bidirectional Immune Modulation

Cordyceps doesn’t just “boost” immunity—it smartly regulates it.

• 🔼 In immunosuppressed states: Enhances NK cells, macrophages, lymphocytes

• 🔽 In overactive states: Lowers pro-inflammatory cytokines, such as TNF-α and IL-6, while increasing IL-10

  
  

It operates through key immune pathways like NF-κB, MAPK, and JAK/STAT. This makes it an ideal support for viral infections, autoimmune conditions, cancer, and chronic inflammation.

6️⃣ Immunity Booster for Long-Term Defense

Cordyceps militaris stimulates both innate and adaptive immunity, improving your body’s defense system on multiple fronts:

• ✅ Boosts T-cells, B-cells, macrophages, and NK cells

• ✅ Enhances antibody production and antigen presentation

• ✅ Regulates cytokine release for a balanced immune response

  
  

With consistent use, it helps the body mount a faster, smarter response to pathogens like SARS-CoV-2.

7️⃣ Breathe Better: Cordyceps & Oxygen Saturation

Used traditionally in Himalayan medicine to combat high-altitude fatigue, modern science backs its effectiveness:

• 📈 2024 clinical trials show improved SpO₂, VO₂ max, and red blood cell function

• 🏃 Athletes reported reduced fatigue and increased endurance

• 🩸 Supports hemoglobin stability and oxygen transport

  
  

💡 Especially helpful during COVID-related hypoxia and respiratory fatigue.

🌿 Final Word: A Multi-Action Natural Ally

From blocking viral entry to balancing your immune system and fighting inflammation, Cordyceps militaris offers a science-backed, holistic approach to COVID-19 prevention and recovery.

If you're looking for a natural, time-tested remedy with modern validation, Cordyceps militaris (Keeda Jadi) deserves a place in your wellness routine.

How much Cordyceps militaris mushroom to Consume

Understanding the Dosage

To decode the long-sought question of quantifying the right dosage of Cordyceps militaris (Keeda Jadi) mushroom, we shall proceed with these two assumptions:

• The average body weight of an adult human is 70 kilograms.

• The average water content in the human body is 60%.

  
  

Now, the amount of water in an adult human body = 60% of 70 kg = 42 kg. Assuming the density of water is 1.000 g per mL, the water content becomes 42.0 liters.

Referring to Amgad M. Rabie, "In line with its potent antiviral-RNA activities, cordycepin also demonstrated a very slight value of the concentration that is needed for 50% in vitro lowering in the number of RNA copies of the VOC-202012/01 strain of SARS-CoV-2 (**2.35 μM**), which is clearly smaller than the corresponding values of both remdesivir and GS-441524 (22.92 and 16.04 μM, respectively)".

To reduce the viral load by 50%, we need:

• Required [Cordycepin] = 2.35 μM

• = (2.35 x 10⁻⁶ moles L⁻¹) x 251.24 g mol⁻¹

• = 0.0005904 g L⁻¹

  
  

Note: Molar mass, cordycepin=251.24 g mol⁻¹

The Required Quantity of Cordycepin from Water Content

Then, accounting for the water content of 42.0 liters in an adult human body, the required quantity of Cordycepin will be:

• Required quantity of Cordycepin = Required [Cordycepin] x Volume of water

• = 0.0005904 g L⁻¹ x 42.0 liters

• = 0.024797 grams Cordycepin

• = 24.80 mg Cordycepin

  
  

Thus, an average adult will need to consume around 24.80 mg of Cordycepin to reduce the viral load by 50%.

Estimating the Quantity of Cordyceps militaris Mushroom

The Cordycepin content of Cordyceps militaris mushroom varies by source. To simplify further calculations, it's assumed that the average cordycepin content in the fruiting body or mushroom sample is 10.0 mg cordycepin per gram of mushroom (dry weight basis).

So, required quantity of Cordyceps militaris mushroom will be:

• Required quantity of Cordycepin / cordycepin content in Cordyceps mushroom

• = 24.80 mg Cordycepin / (10.0 mg Cordycepin / gram Cordyceps mushroom)

• = 2.48 grams Cordyceps mushroom.

  
  

Thus, an adult human should take 2.48 grams of Cordyceps mushroom.

What is the maximum quantity of Cordyceps militaris mushroom that anyone can Consume?

Cytotoxicity assays conducted by Amgad M. Rabie indicate that the in vitro CC₅₀ (concentration required to reduce cell viability by 50%) of cordycepin exceeds 100 μM. This suggests low toxicity and a favorable safety profile.

To put this into perspective, a 100 μM concentration of cordycepin corresponds to approximately 105.52 grams of dried Cordyceps militaris mushroom, based on values discussed earlier.

Theoretically, consuming about 105.52 grams of dried Cordyceps militaris could reach cytotoxic levels for 50% of human cells in vitro. However, it's important to emphasize that this estimate is purely theoretical and does not reflect real-world toxicity in the human body (in vivo).

Therefore, for safety, actual human consumption should remain well below the 105.52-gram threshold.

How Much Cordyceps militaris Should You Take? A Practical Guide Based on Real Observations

No Official Dosage—But Here's What We Know

There are no official or standardized guidelines that define the optimal daily dose of Cordyceps militaris for humans. The ideal quantity can vary based on several factors, such as:

• Cordycepin concentration in the mushroom sample

• Body weight and metabolism of the individual

• EC₅₀ (Effective Concentration 50%) of the target pathogen (2.35 μM for SARS-CoV-2)

• Viral load or severity of infection

• General health status and immune response variability

  
  

Despite these variables, most scientific literature agrees that Cordyceps militaris is extremely safe for human consumption, with an estimated safe intake range of 1 to 10 grams per day (dry weight).

My 2-Year Experience with Cordyceps militaris

For the past two years, I have consumed my lab-grownCordyceps militaris
almost daily. Based on personal experience and feedback from hundreds of customers, I’ve compiled the following dosage insights and health benefits:

🌿 Recommended Daily Dosage: 1 Gram

✅ For General Health and Well-Being

Dose: ~1.0 gram of dried Cordyceps militaris (Keeda Jadi)

Best time: At night before bed.

This modest dose supports overall vitality, better sleep, and improved immune response.

✅ Relief from Cold, Cough & Respiratory Symptoms

• Symptom relief in ~1 hour after drinking Cordyceps tea (1.0 gram)

• ~50% symptom reduction overnight for common cold, sore throat, cough.

  
  

✅ Chronic Cough & Allergies

• 1.0 gram/day before bed may significantly reduce persistent coughs (including allergic and nighttime coughing)

• Results in 5–7 days.

  
  

✅ Joint Pain & Arthritis

• Relief within 1–2 weeks of daily consumption

• Reduces inflammation and eases joint discomfort.

  
  

✅ Asthma Support

• 1.0 gram/day for 15–30 days

• Helps reduce inhaler use from 3 times/day to 1 time/day or even discontinue in some cases.

  
  

The most effective way to prepare Cordyceps tea is illustrated here:

Read Preparation of Cordyceps militaris (Keeda Jadi) Tea for maximal benefits.

🦠 Cordyceps militaris & COVID-19: Dosage Insights

Based on theoretical calculations and preliminary research, the optimum dosage for COVID-19 prevention and support is around 2.48 grams per day.

📌 For Active SARS-CoV-2 Infection:

• Drink 1–2 grams of Cordyceps tea, 2–3 times daily.

• A nighttime dose is essential for best results, as the body repairs and regulates immunity during sleep.

  
  

🧪 How to Take Cordyceps militaris (Keeda Jadi) Mushroom?

Forms, Effectiveness & Best Use for Respiratory Infections

🍄 Available Forms of Cordyceps militaris

• ✅ Fresh or dried fruiting body (mushroom)

• ✅ Powder

• ✅ Capsules

• ✅ Tea bags

• ✅ Liquid extracts

• ✅ Herbal blends (with other botanicals)

  
  

📘 See comparison guide: [*The Best Way to Consume Cordyceps militaris](/post/the-best-way-to-consume-cordyceps-militaris)
.

☕ Why Cordyceps Tea Works Best for Respiratory Infections

🔬 Targeted Absorption: While drinking tea, cordycepin and other active compounds are absorbed through the mucosal lining of the mouth and upper respiratory tract.

⏱️ Faster Relief (within ~30 minutes) Ideal for:

• Sore throat

• Nasal congestion

• Inflammation of upper airways

• Runny nose

  
  

🌡️ Enhanced Effectiveness: When made properly from Cordyceps powder, tea boosts digestibility and bioavailability of therapeutic compounds.

📘 Learn how to make it: [*Preparation of Cordyceps militaris (Keeda Jadi) Tea for Maximal Benefits](/post/prepare-cordyceps-tea)
.

🇮🇳 Proudly Cultivated in India

Explore premium Cordyceps products at 👉 www.agripie.com.

🛑 Side Effects of Cordyceps militaris Mushroom

The calculated CC₅₀ value of approximately 105.52 grams (based on specific assumptions) is significantly higher than the typical recommended daily intake of 1–10 grams of dried Cordyceps militaris. This wide margin indicates that the mushroom has low toxicity and a strong safety profile when consumed responsibly.

That said, a small number of individuals may experience minor side effects, such as:

• Dry mouth – This may occur because Cordyceps enhances the body’s water retention to improve osmoregulation. Staying well hydrated can help minimize this effect.

• Mild stomach discomfort or indigestion.

  
  

These side effects are rare, mild, and temporary, usually resolving within a day or two after discontinuing use.

⚠️ Important: Individuals with mushroom allergies may experience allergic reactions. If you have a known sensitivity to fungi or mushrooms, it is strongly recommended to consult a healthcare professional before consuming Cordyceps militaris.

Disclaimer: This content is for informational purposes only and is not a substitute for professional medical advice. Always consult your healthcare provider before using any supplement, especially during active illness.

References:

1. Rabie, A. M. (2022). Potent inhibitory activities of the adenosine analogue cordycepin on SARS-COV-2 replication. ACS Omega, 7(3), 2960–2969. https://doi.org/10.1021/acsomega.1c05998

2. Bibi S, Hasan MM, Wang YB, Papadakos SP, Yu H. Cordycepin as a Promising Inhibitor of SARS-CoV-2 RNA Dependent RNA Polymerase (RdRp). Curr Med Chem. 2022;29(1):152-162. doi: 10.2174/0929867328666210820114025. PMID: 34420502.

3. Baig MH, Turk A, Vishwakarma P, Jo YS, Dong JJ, Lee DH, Kim YG, Lee MK, Cho JY. Exploring the Therapeutic Potential of Cordyceps Mushroom on SARS-CoV-2 Using Virtual Screening against Mpro and In Vitro Validation of Cordycepin. J Microbiol Biotechnol. 2025 Mar 26;35:e2411063. doi: 10.4014/jmb.2411.11063. PMID: 40147924; PMCID: PMC11985406.

4. Gandhale, P., Chikhale, R., Khanal, P., Biswa, V., Ali, R., Khan, M. S., Gurav, N., Ayyanar, M., Das, S., & Gurav, S. (2024). Quest for Anti-SARS-CoV-2 antiviral therapeutics: in-silico and in-vitro analysis of edible mushroom- Cordyceps militaris. Journal of Ayurveda and Integrative Medicine, 15(3), 100979. https://doi.org/10.1016/j.jaim.2024.100979

5. Iwasaki M, Saito J, Zhao H, Sakamoto A, Hirota K, Ma D. Inflammation Triggered by SARS-CoV-2 and ACE2 Augment Drives Multiple Organ Failure of Severe COVID-19: Molecular Mechanisms and Implications. Inflammation. 2021 Feb;44(1):13-34. doi: 10.1007/s10753-020-01337-3. Epub 2020 Oct 8. PMID: 33029758; PMCID: PMC7541099.

6. Singh, M., Verma, H., Gera, N., Baddipadige, R., Choudhary, S., Bhandu, P., & Silakari, O. (2023). Evaluation of Cordyceps militaris steroids as anti-inflammatory agents to combat the Covid-19 cytokine storm: a bioinformatics and structure-based drug designing approach. Journal of Biomolecular Structure and Dynamics, 42(10), 5159–5177. https://doi.org/10.1080/07391102.2023.2245039

7. Jing Du, Weijing Kan, Hongkun Bao, Yue Jia, Jian Yang, Hongxiao Jia, Interactions Between Adenosine Receptors and Cordycepin (3-Deoxyadenosine) from Cordyceps Militaris: Possible Pharmacological Mechanisms for Protection of the Brain and the Amelioration of Covid-19 Pneumonia. Journal of Biotechnology and Biomedicine 4 (2021): 26-62.

8. Dubhashi S, Sinha S, Dwivedi S, Ghanekar J, Kadam S, Samant P, Datta V, Singh S, Chaudry IH, Gurmet P, Kelkar H, Mishra R, Galwankar S, Agrawal A. Early Trends to Show the Efficacy of Cordyceps militaris in Mild to Moderate COVID Inflammation. Cureus. 2023 Aug 18;15(8):e43731. doi: 10.7759/cureus.43731. PMID: 37727187; PMCID: PMC10505833.

9. Yuanyuan Chen, Guang Chen and Cheng Zhang et al. Randomized, waitlist-controlled trial of Cordyceps sinensis mycelium culture extract (Cs4) for long COVID patients in Hong Kong. Acta Materia Medica. 2025. Vol. 4(2):250-261. DOI: 10.15212/AMM-2024-0089

10. Singh M, Tulsawani R, Koganti P, Chauhan A, Manickam M, Misra K. Cordyceps sinensis increases hypoxia tolerance by inducing heme oxygenase-1 and metallothionein via Nrf2 activation in human lung epithelial cells. Biomed Res Int. 2013;2013:569206. doi: 10.1155/2013/569206. Epub 2013 Aug 26. PMID: 24063008; PMCID: PMC3770031.

11. Pasha, S. M., Rajan, A. N., Rathod, L., Musfera, S., & Pasha, C. (2024). Improved Oxygen Saturation and Performance of Athletes using Cordyceps militaris. Asian Journal of Biological Sciences, 17(1), 85–92. https://doi.org/10.3923/ajbs.2024.85.92

12. Hirsch KR, Smith-Ryan AE, Roelofs EJ, Trexler ET, Mock MG. Cordyceps militaris Improves Tolerance to High-Intensity Exercise After Acute and Chronic Supplementation. J Diet Suppl. 2017 Jan 2;14(1):42-53. doi: 10.1080/19390211.2016.1203386. Epub 2016 Jul 13. PMID: 27408987; PMCID: PMC5236007.

13. Nakamura, A.; Shinozaki, E.; Suzuki, Y.; Santa, K.; Kumazawa, Y.; Kobayashi, F.; Nagaoka, I.; Koikawa, N. Effect of the Administration of Cordyceps militaris Mycelium Extract on Blood Markers for Anemia in Long-Distance Runners. Nutrients 2024, 16, 1835. https://doi.org/10.3390/nu16121835