Disclaimer: Covid.us.org offers explanations of recent research into Covid-19 for informational purposes only. For treatment of Covid-19, see your healthcare provider. Nothing said herein is intended to constitute or replace medical care or advice. The information provided in this website is for educational purposes only and not intended to be a substitute for professional medical advice. Please consult your doctor before making any healthcare decisions, especially if you or a family member are ill.

This List is based on the theory that LongCovid is caused by infection of the CNS with SARS-CoV-2. See these articles on the theory:
* Does coronavirus linger in the body? by William Petri, MD, PhD
* What Causes LongCovid? What Causes Hair Loss in Covid-19?
* The Longhaulers Hidden Virus Hypothesis
* Longhaulers happens when the virus hides in Immune Privileged Cells
* What Causes Longhaulers Syndrome? (LongCovid)
* Infection of the Brain by Covid-19 Explains LongCovid

The main Immune Privileged Site believed to be infected by SARS-CoV-2 (the virus that causes Covid-19) is the CNS (central nervous system), which of course includes the brain and the cranial nerves. There’s not a single symptom of LongCovid that is not explained by this theory.

Possible Treatments for LongCovid

Steroids

Dr. Mobeen Syed has repeatedly said in his videos and on Twitter here that he treats his LongCovid patients with a steroid pulse:

Deltacortril (i.e. prednisolone or prednisone)

Days 1 and 2: 5 mg three times a day
(once with breakfast, once with lunch, once with dinner)

Days 3 and 4: 5 mg twice a day
(once with breakfast, once with lunch)

Days 5 and 6: 5 mg once a day
(once with breakfast)

#LongCovid #Longhaulers

Dr. Mobeen has stated that this has worked with all of his LongCovid patients. In one case, he had to repeat the steroid pulse above a second time. Otherwise, it has worked so far for his LongCovid patients.

However, some LongCovid patients online have stated that treatment with steroids has helped them a great deal, but then the symptoms return. It is not an effective treatment for everyone.

Ivermectin

Important: Do NOT take ivermectin with steroids. Again, never take ivermectin during the same period of time that you are taking steroids. The steroids allow the ivermectin to cross the BBB and that can cause brain damage. How long after you stop taking steroids can you then begin taking ivermectin? I don’t know. Ask your physician.

A Longhauler has stated that she takes ivermectin once a week. She states that it relieves 80 to 90% of her symptoms, but then the symptoms return after about a week.

To my mind, this provides more support for the theory that LongCovid is caused by infection of CNS by SARS-CoV-2. The CNS is behind the Blood Brain Barrier (BBB), and ivermectin does not cross the BBB. So ivermectin can clear the virus outside of the CNS, relieving many symptoms. But then the virus multiplies within the CNS and spreads again.

WHAT IS NEEDED IS ANTI-VIRALS THAT CROSS THE BBB.

Molecular docking studies indicate that certain natural compounds, available as OTC Supplements, bind to viral components, slowing the viral infection and replication. Multiple inhibitors are needed for a substantial effect on the virus. The supplements below were chosen based on multiple docking studies, solubility, absorption, ability to cross the BBB, and possible neuroprotective effects, all based on the premise that LongCovid is an infection of SARS-CoV-2 in immune privileged sites, especially the CNS (brain, cranial nerves, etc.). Why do Longhaulers often have the symptom of hair falling out? Anagen hair follicles are immune privileged sites. It’s proof of the theory.

Doxycycline plus Vitamin C
100 mg of doxycycline twice a day
500 mg of vitamin C, 2 to 4 times a day

* crosses the BBB
* inhibits multiple viral proteins
* anti-inflammatory
* good safety profile
* may work synergistically with Vitamin C

Doxycycline has “anti-inflammatory activities (Balducci et al., 2018), a good blood–brain barrier (BBB) penetration, and a safe pharmacological profile.” [1]

Vitamin C may work synergistically with doxycycline to reduce inflammation and inhibit viral replication [3].

Doxycycline also functions as a viral inhibitor of SARS-CoV-2, specifically against: Mpro, PLpro, Spike protein, Nsp3, 12, 15, 16, and ACE2 [4].

Vitamin C is also a viral inhibitor of multiple SARS-CoV-2 targets, though with more moderate docking scores [5].

Vitamin C crosses the BBB and is present in the brain at a level 10-fold the blood level [6].

Vitamin C
500 mg of vitamin C, 2 to 4 times a day (time-released version preferred)

“Vitamin C concentrations in the brain exceed those in blood by 10-fold. In both tissues, the vitamin is present primarily in the reduced form, ascorbic acid. We identified the chemical form of vitamin C that readily crosses the blood-brain barrier, and the mechanism of this process. Ascorbic acid was not able to cross the blood-brain barrier in our studies. In contrast, the oxidized form of vitamin C, dehydroascorbic acid (oxidized ascorbic acid), readily entered the brain and was retained in the brain tissue in the form of ascorbic acid.” [6]

Riboflavin
100 mg of riboflavin, 4 times a day.

In the human body, riboflavin is turned into flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN). All three compounds are good inhibitors of multiple SARS-CoV-2 components (see this review). Riboflavin crosses the BBB readily [8], as the human body is designed to transport and use Vitamin B2 (riboflavin) in many different cell types, including neurons in the brain and astrocytes (support cells for the nervous system in the CNS). Thus, riboflavin is an ideal inhibitor of SARS-CoV-2, if/when it infects the CNS.

Other Vitamins

These vitamins act as viral inhibitors. They are not being taken for their effects as vitamins, but as a type of medication that binds to viral proteins and inhibits those components. This is the same mechanism of action as some other Covid-19 treatments, such as lopinavir, favipiravir, azithromycin, etc. Note that antibiotics are sometimes given to Covid-19 patients for their anti-viral effects, not for their anti-bacterial effects. This is termed drug re-purposing. In this case, vitamins are being re-purposed as viral inhibitors.

Vitamin K1 – 1500 micrograms 1x/day
Thiamine – 25 mg, 4x/day
Vitamin B12 – 2,500 micrograms 2x/day

Quercetin

Quercetin crosses the BBB [14] and is an effective inhibitor of multiple viral proteins of SARS-CoV-2, the virus that causes Covid-19. Quercetin is recommended by the MATH+ protocol for treatment and prevention of Covid-19.

WebMD on Quercetin risks

Green Tea Extract
400 mg twice a day (50% EGCG and 30% other Catechins)

The active components of Green Tea Extract (GTE) are EGCG and other Catechins.

In an in vitro study of SARS-CoV-1 (the virus that causes SARS), inhibition of the N-protein (nucleocapsid) to 40% only required a concentration of 0.05 µg/ml or 50 ng/ml for CG and GCG [11]. CG is (-)-catechin gallate and GCG is (-)-gallocatechin gallate. So even with low permeation of the BBB, GTE seems like a good supplement to take for LongCovid. And in the bloodstream and the body outside the CNS, GTE is present in much higher concentrations, and can inhibit the virus more effectively there.

WebMd on Green Tea Extract

Melatonin

A new study found that melatonin is positively associated with survival and better outcomes for Covid19, esp. in severe cases: Study Link. Take 0.3 mg (300 micrograms) once in the evening, and gradually increase dose to 2 to 6 mg range.

Milk Thistle

Silybin and Silymarin, two compounds in milk thistle extract, have been found by some molecular docking studies to be inhibitors of SARS-CoV-2, the virus that causes Covid-19. They also cross the BBB and seem to have neuroprotective effects [15].

Who should NOT take Milk Thistle (silymarin, silybin)? See WebMD Side Effects. Be cautious of mild thistle if you are allergic to rag weed or similar plants/pollen.

Hesperidin

“The need for antioxidants to penetrate the blood-brain barrier(BBB) is a mandatory prerequisite for them to be considered as a potential neuroprotective agent and hesperidin is meth-oxylated citrus flavonoid and hence lipophilic in nature, a requisition for BBB penetration. There are several reports that hesperidin crosses BBB (Dimpfel, 2006; Hwang and Yen, 2008; Youdim et al., 2003)”. [9]

Hesperidin is a strong inhibitors of SARS-CoV-2, as determined by about 30 different molecular docking studies.

Curcumin

A strong inhibitor of SARS-CoV-2, identified by many molecular docking studies. Low absorption and low ability to cross BBB, but liposomal curcumin may solve those problems.

Theaflavin

Black tea extract contains theaflavin, a highly effective inhibitor of SARS-CoV-2 in docking studies and in SARS-CoV-1 in vitro studies.

Rutin

Rutin is perhaps as effective as quercetin, but they are mutually exclusive. Some of the Rutin is turned into quercetin in the body, so taking both may result in an excessive amount of quercetin.

Platycodon grandiflorus extract

Also called balloon flower root or bell flower root extract. Contains platycodin D which is a strong inhibitor of the Covid-19 virus. PGE is widely used in South Korea as a medicinal extract and supplement.

Ecklonia cava extract

ECE contains multiple compounds that inhibit SARS-CoV-2.

Resveratrol

MDS 83: high absorption and BBB permeant
over a dozen molecular docking studies show that resveratrol inhibits SARS-CoV-2.

WebMD on Resveratrol

Ronald L. Conte Jr.
Covid.us.org
an author, not a doctor

ENDNOTES

Endnotes marked “MDS ##” are found at the particular numbered reference on this page: The Covid-19 Molecular Docking Studies List.

1. Balducci, Claudia, and Gianluigi Forloni. “Doxycycline for Alzheimer’s disease: fighting β-amyloid oligomers and neuroinflammation.” Frontiers in Pharmacology 10 (2019): 738.

2. Lucchetti, Jacopo, et al. “Plasma and brain concentrations of doxycycline after single and repeated doses in wild-type and APP23 mice.” Journal of Pharmacology and Experimental Therapeutics 368.1 (2019): 32-40.

3. Szolnoky, Győző. “Further aspects of doxycycline therapy in COVID‐19.” Dermatologic Therapy (2020).

4. Maurya, Dharmendra Kumar. “A Combination of Ivermectin and Doxycycline Possibly Blocks the Viral Entry and Modulate the Innate Immune Response in COVID-19 Patients.” (2020).

5. Fatoki, Toluwase Hezekiah, et al. “Network analysis, sequence and structure dynamics of key proteins of coronavirus and human host, and molecular docking of selected phytochemicals of nine medicinal plants.” Journal of Biomolecular Structure and Dynamics (2020): 1-23.

6. Agus, David B., et al. “Vitamin C crosses the blood-brain barrier in the oxidized form through the glucose transporters.” The Journal of clinical investigation 100.11 (1997): 2842-2848.

7. MDS 183

8. Moriyama, Yoshinori. “Riboflavin transporter is finally identified.” The Journal of Biochemistry 150.4 (2011): 341-343.

9. Raza, Syed Shadab, et al. “Hesperidin ameliorates functional and histological outcome and reduces neuroinflammation in experimental stroke.” Brain research 1420 (2011): 93-105.

10. Wu, Liang, et al. “Pharmacokinetics and blood–brain barrier penetration of (+)-catechin and (−)-epicatechin in rats by microdialysis sampling coupled to high-performance liquid chromatography with chemiluminescence detection.” Journal of Agricultural and Food Chemistry 60.37 (2012): 9377-9383.

11. Roh, Changhyun. “A facile inhibitor screening of SARS coronavirus N protein using nanoparticle-based RNA oligonucleotide.” International journal of nanomedicine 7 (2012): 2173.

12. MDS 84

13. MDS 149

14. Ren, S. C., et al. “Quercetin permeability across blood-brain barrier and its effect on the viability of U251 cells.” Sichuan da xue xue bao. Yi xue ban Journal of Sichuan University. Medical science edition 41.5 (2010): 751.

15. Borah, Anupom, et al. “Neuroprotective potential of silymarin against CNS disorders: insight into the pathways and molecular mechanisms of action.” CNS neuroscience & therapeutics 19.11 (2013): 847-853.