By Doris Loh
This article is a condensed version containing important slides from the video presentation “Ancient Molecules for Healthy Hearts”. Slides may be copied and reproduced, provided proper credit is given. The entire video can be viewed by following this link: https://www.youtube.com/watch?v=JsO-XlUHsV0&feature=emb_logo
The SARS-CoV-2 pandemic has now infected over 41 million people worldwide. Fortunately, the death rates are extremely low. The most concerning development in the understanding of this virus is how heart health is impacted during and after infections.
The reason why SARS-CoV-2 is less lethal but more infectious is due to a mutation called D614G that is now the predominant strain globally.
This mutation may change the conformation of the receptor binding area in the spike protein, potentially making it easier for the virus to bind to cell receptors.
The D614G mutation may also make it easier for the virus to be cleaved and activated by host proteases. The SARS-CoV-2 virus is unique in that not only is it cleaved by furin, which is widely expressed in all tissues, it can be cleaved by many other proteases.
This is the reason why COVID-19 can cause damage to many other organs in addition to lungs in the respiratory system.
The fact that heart damage is commonly reported in COVID-19 patients regardless of age, and that heart injuries may persist long after recovery is troubling.
Since viral particles were found during autopsies in many types of heart tissues of patients infected by SARS-CoV-2, it is not surprising that the virus can directly attack heart muscles.
SARS-CoV-2 has been shown to cause fragmentation to sarcomeres, which are fibers responsible for heart muscle contractions.
The virus can damage sarcomeres because it can bind enzymes called integrins via the RGD motif in the spike protein. This area is the same one that has become exposed as a result of the conformation changes resulting from the D614G mutation.
Integrins are transmembrane receptors that modulate protein connection structures in sarcomeres. If they are deficient, sarcomeres can become fragmented and lose the ability to support proper heart muscle contractions.
Individuals with deficient integrins due to genetic defects may suffer from heart disease called arrhythmogenic right ventricular cardiomyopathy (ARVC). The lack of integrins in this disease causes arrythmias.
Unfortunately, integrin receptors also mediate viral infections, including SARS-CoV2.
Sarcomeres fragmented as a result of SARS-CoV-2 infection are almost identical to sarcomeres deficient in integrins in patients with ARVC.
Interestingly, right ventricular dysfunctions have been observed in 39% of hospitalized COVID-19 patients.
Even long after recovery, SARS-CoV-2 can still affect normal heart functions. This makes protecting the heart a primary focus during COVID-19 pandemic.
How Do We Protect Our Hearts from SARS-CoV-2?
SARS-CoV-2 is a coronavirus. Viruses are ancient, they have evolved with all living organisms for over 3 billion years.
How did living organisms manage to survive and thrive together with viruses? Nature provided all living organisms with two fundamental and critical molecules that evolved together with viruses from over 3 billion years ago. These two molecules continue to protect living organisms today against virus attacks.
Ascorbic Acid (AA)
Melatonin has been shown to be effective against a wide array of symptoms presented during COVID-19 infections [Ref. 1-11].
Supplementation with melatonin is especially effective in increasing endogenous melatonin production in mitochondria.
Adequate melatonin in mitochondria of macrophages can reduce pro-inflammatory phenotypes, reducing cytokine storms.
Melatonin can protect sarcomeres from SARS-CoV-2 fragmentation by increasing production of integrins.
This is one of the main reasons why melatonin has been found to be able to protect the heart during COVID-19 infections.
Ascorbic Acid (AA), commonly known as Vitamin C is used in treatments for heart dysfunctions caused by viral infections.
Ascorbic acid is able to protect the heart during SARS-CoV-2 infections because it is a redox molecule favored by plasma membrane redox enzymes like CYB5R3 found in abundance in the heart.
CYB5R3 uses ascorbic acid to perform electron exchanges so as to maintain iron ions in stable forms that can bind oxygen.
When CYB5R3 cannot replenish electrons in oxidized heme iron using ascorbic acid, the heme destabilize and becomes toxic cell free heme that can damage the heart.
Ascorbic acid is also used by macrophages to kill pathogens and prevent excess buildup of pro-inflammatory phenotypes that can cause cytokine storms.
Living organisms have been using melatonin and ascorbic acid against viruses for over 3 billion years. We should do the same.
Summary & Links to Articles
Have you had your AA and MEL today?
 Tan DX, Hardeland R. Targeting Host Defense System and Rescuing Compromised Mitochondria to Increase Tolerance against Pathogens by Melatonin May Impact Outcome of Deadly Virus Infection Pertinent to COVID-19. Molecules. 2020 Sep 25;25(19):E4410. doi: 10.3390/molecules25194410. PMID: 32992875.
 Tesarik, J. 2020. Melatonin attenuates growth factor receptor signaling required for SARS-CoV-2 replication. Melatonin Research. 3, 4 (Oct. 2020), 534-537. DOI:https://doi.org/https://doi.org/10.32794/mr11250077.
 Dominguez-Rodriguez, A., Abreu-Gonzalez, P., Marik, P.E. and Reiter, R.J. 2020. Melatonin, cardiovascular disease and COVID-19: A potential therapeutic strategy?. Melatonin Research. 3, 3 (Jun. 2020), 318-321. DOI:https://doi.org/https://doi.org/10.32794/mr11250065.
 Hardeland, R. and Tan, D.-X. 2020. Protection by melatonin in respiratory diseases: valuable information for the treatment of COVID-19. Melatonin Research. 3, 3 (Jun. 2020), 264-275. DOI:https://doi.org/https://doi.org/10.32794/mr11250061.
 Cardinali, D.P. 2020. High doses of melatonin as a potential therapeutic tool for the neurologic sequels of covid-19 infection. Melatonin Research. 3, 3 (Jun. 2020), 311-317. DOI:https://doi.org/https://doi.org/10.32794/mr11250064.
 Anderson, G. and Reiter, R.J. 2020. COVID-19 pathophysiology: interactions of gut microbiome, melatonin, vitamin D, stress, kynurenine and the alpha 7 nicotinic receptor: Treatment implications. Melatonin Research. 3, 3 (Jun. 2020), 322-345. DOI:https://doi.org/https://doi.org/10.32794/mr11250066.
 Boga, J.A. and Coto-Montes, A. 2020. ER stress and autophagy induced by SARS-CoV-2: The targets for melatonin treatment. Melatonin Research. 3, 3 (Jun. 2020), 346-361. DOI:https://doi.org/https://doi.org/10.32794/mr11250067.
 Reiter, R.J., Sharma, R., Ma, Q., Liu, C., Manucha, W., Abreu-Gonzalez, P. and Dominguez-Rodriguez, A. 2020. Plasticity of glucose metabolism in activated immune cells: advantages for melatonin inhibition of COVID-19 disease. Melatonin Research. 3, 3 (Jun. 2020), 362-379. DOI:https://doi.org/https://doi.org/10.32794/mr11250068.
 Loh, D. 2020. The potential of melatonin in the prevention and attenuation of oxidative hemolysis and myocardial injury from cd147 SARS-CoV-2 spike protein receptor binding. Melatonin Research. 3, 3 (Jun. 2020), 380-416. DOI:https://doi.org/https://doi.org/10.32794/mr11250069.
 Pal, P.K., Chattopadhyay, A. and Bandyopadhyay, D. 2020. Melatonin as a potential therapeutic molecule against COVID-19 associated gastrointestinal complications: An unrevealed link. Melatonin Research. 3, 3 (Jun. 2020), 417-435. DOI:https://doi.org/https://doi.org/10.32794/mr11250070.
 Castillo, R.R., Quizon, G.R.A., Juco, M.J.M., Roman, A.D.E., de Leon, D.G., Punzalan, F.E.R., Guingon, R.B.L., Morales, D.D., Tan, D.-X. and Reiter, R.J. 2020. Melatonin as adjuvant treatment for coronavirus disease 2019 pneumonia patients requiring hospitalization (MAC-19 PRO): a case series. Melatonin Research. 3, 3 (Jun. 2020), 297-310. DOI:https://doi.org/https://doi.org/10.32794/mr11250063.