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Lysine Therapy for SARS-CoV-2

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  • Bio-Virus Research Inc.
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  • Bio-virus research
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Lysine Therapy for SARS-CoV-2        
Christopher Kagan, Alexander Chaihorsky, Rony Tal, Bo Karlicki.
Until treatments with wide universality across target viral families become a reality,
pandemics will continue to inflict severe medical and economic losses on the world's
population, as the current situation demonstrates. Both therapeutic and vaccine arms of
viral defense should be developed with universality in mind, and our group, Bio-
Virus Research, has been working on both universal vaccines and universal
therapeutic approaches for decades. In this letter we report our current results using L-
lysine therapeutically against SARS-CoV-2.        
The first report of the clinical use of L-lysine, written by the lead author of this article,
appeared in The Lancet in 1974. (1) The mechanism of action and clinical follow up
confirming its effectiveness in the treatment of herpes was published in 1978 (2), and in-
vitro confirmation of the inhibition of arginine by lysine was published in 1985. (3) Since
then L-lysine supplementation with arginine restriction has become a recognized
treatment worldwide, and the generally used dosage ranges between 100 mg to 4
grams a day; notably no toxicity has been reported with up to 8 grams per day.
(4) Lysine therapy appears to apply universally across the entire family of herpes viruses
with no exceptions reported. Examples in humans include cytomegalovirus and zoster.
(2) Lysine has been shown to be suppressive in both RNA and DNA viruses, examples
include the RNA-type mouse encephalomyelitis virus, and the DNA-type adenovirus
type 1, SV 40, and polyoma, and the herpes virus in chickens that causes Marek's
disease is known to be arginine dependent. (2) The action of lysine is complex with
interference of L-arginine incorporation into the virus by L-lysine established. (2)
(3) Lysine inhibits arginine absorption in the intestine competitively lowering arginine
levels, as well as inhibiting arginine reabsorption in the renal tubules. (2) A more
complex mechanism with respect to SARS-CoV-2 is strongly suggested in multiple
references which lay a foundation for further investigation beyond the scope of this
clinical report. (6) (9) (10) (11) (12) (17) (20) (23)      
A report in 2016 which included L-lysine showed a positive clinical outcome against
MERS-CoV in-vitro, although not SARS-CoV-2 which had not yet appeared. (5) Given that
L-lysine appears to operate universally within the herpes viral family, it would be
reasonable to expect it to work in the entire SARS viral family. Our clinical experience
demonstrates effectiveness against SARS-CoV-2, and it is therefore likely to work in
MERS-CoV and other members of the Coronavirus family in-vivo. Dietary lysine
deficiency is known to impair both antibody responses and cell-mediated immune
response. (7) Lysine improves the immune system. (4)    
We tested the clinical efficacy of lysine on SARS-CoV-2. Tabulated data from 40 +
subjects, and non-tabulated data from 100+ subjects; 8 were in the United States, and
the majority in the Dominican Republic. The age ranged between 16 to 77, with 55% of
the tabulated group being female. Approximately 50% of the subjects were PCR or rapid
test Covid confirmed. Approximately 50% were febrile, 30% had cough/throat, 35%
anosmia, 50% CNS/muscle pain, and 45% had other symptoms.        
The dose range administered was 1000 mg to 4000 mg, with the latter rarely given, and
an average dose of 2000 mg. We do not recommend exceeding 3000 mg due to
possible bradykinin buildup causing a cough or increasing coughing in some subjects.
(19) The dosage schedule recommended based on our study for acute cases (less than 1
month with symptoms) is a base dose of 1000 mg twice on day 1, increasing, if needed,
by 500 mg to 1000 mg for a total not exceeding 3000 mg on day 2. From day 3 forward,
some patients may require as high as 3500 mg. The recommended treatment times are
one hour before breakfast, and 3 pm on day 1 with the times advanced earlier in the
afternoon on day 2 if needed, opening a 9 pm time slot for a third dose. All doses
should be taken a minimum of 1 hour before a meal, and with two cups of water. Two
cups of water aids in absorption, hydration, anticoagulation, and dampens appetite
which results in a decrease in the quantity of unintended arginine ingestion. A first day
emergency dose of 2000 mg together (try not to exceed 4 grams in total on day 1) or a
few hours apart yields outstanding results. There are many charts available of
the lys/arg ratios in various foods, and a dietary ratio of 2.0 to 3.0 lysine to 1.0 arginine
for the first few days is recommended. The ratio can be lowered to 1.5 to 3.0 lysine to 1.0
arginine once near full symptom control is achieved. Restriction of coffee (and other
high caffeine drinks), the importance of which cannot be stressed enough, and
observing the arginine restricted diet is critical to the speed of recovery and success of
treatment. Additional cautionary notes are listed at the bottom of the letter, and these
cautions should be observed in follow-up clinical studies.        
No trend was noted between sexes, ages, or co-morbidities in relation to lysine
treatment. Approximately 80% of acute stage Covid-19 sufferers given lysine displayed a
minimum 70% reduction in symptoms in the first 48 hours (not including long term
symptomatic subjects). Excluding long term subjects, treatment times vary from 2 days
to 3.5 weeks, with many variables at play. Patients who started lysine in the hospital were
discharged an average of 3 days after starting treatment. Treatment should be continued
regardless of negative results, until low dose lysine is reached, and no symptoms are
observed. Even when lysine was in short supply, subjects on 2 grams on day 1, and 1
gram the following days, while adhering to the dietary restrictions, had slightly delayed
but timely recoveries. Resuming physical activity too early during recovery sometimes
resulted in setbacks.Several of the inpatients, tabulated and non, after starting this
protocol were RT-PCR negative on day 2 to 3, coinciding typically with their discharge. A
larger sample size and randomized controlled trials with RT-PCR daily testing will be
required to assess the true time to conversion to seronegative. Five patients who fasted
on day 1, due to lack of appetite, were noted to have a significant reduction in the time
and severity of febrile and non-febrile symptoms. It is assumed that zero food intake
equated to no arginine consumed, and hence faster response time. For this group, the
time to significant reduction in symptom varied from 4 hours to 18 hours (with only a
few symptoms remaining). It is important to note that while the average subject may be
completely asymptomatic on day 3 or 4, if they stop treatment/exhaust lysine supply, on
many occasions, symptoms return, albeit usually reduced in severity. Typically for this
group, symptoms abate within a few hours of resuming their lysine.        
Lysine is a treatment, not a cure, and is dependent on the immune system response
gathering momentum to further control the illness. All should remain on at least a
maintenance dose of 1 gm for a minimum of a 1 week (preferably 2 weeks or more)
after all symptoms have abated including following dietary restrictions for 3 weeks to
prevent relapse. Evidence of asymptomatic clotting for those who stopped the regimen
too early was observed. Coffee (associated arginine increase) can overwhelm lysine
rendering it ineffective until the caffeine effect subsides. The caffeine effect displaces
lysine from the metabolic pathways. (18) Coffee/high caffeine consumption was the
most common behavior of long term symptomatic subjects, followed by a
vegetarian/lysine deficient diet and exercising. Coffee/high caffeine drinks should be
avoided during treatment and for 3 weeks after recovery at a minimum. Our treatment
protocol has been used in more than 180 patients, with 40+ reported here. Only 1
subject was hospitalized after starting lysine for secondary bacterial infection.He was
discharged 6 days later, with no long-term effects. One Covid-19 confirmed fatality due
to secondary bacterial infection occurred. Obviously more studies, including randomized
controlled trials, are required for full clinical understanding.        
One of the most important observations in relation to lysine was the incredibly short
time to eliminate/reduce fever presumably due to extinguishing the associated cytokine
storm. Cytokine storm appears to be extinguished in hours, based on the 5 inpatients
who appeared to be in severe crisis when lysine was administered who showed very
rapid reduction in symptoms and stabilization. CRP levels returned to normal, yet D-
dimer levels were high in some subjects.Only a small percentage of subjects on lysine
were febrile past 24 hours, and most were relieved in less than 12 hours with proper
doses and dietary restrictions. IL-10 inhibits the synthesis of IL-6, TNF and IL-1 beta
which are implicated in fever. (8) IL-10 serves as an endogenous antipyretic. (8) Lysine
deficiency raises IL-6 inflammatory cytokine levels, so lysine potentially has an IL-6
inhibitory effect, and lysine also increases IL-10 anti-inflammatory cytokines as shown in
the liver. (7) Therefore, it is logical to assume that supplementation with lysine could
restore or augment IL-10 levels resulting in downregulating proinflammatory cytokines,
in turn eliminating fevers and cytokine storms. IL-6 inhibitors for patients with severe
Covid-19 are associated with decreased intubation, reduced mortality, and increased
discharge. (13) L-lysine decreases nitric oxide production (14), thereby limiting a key role
in the pathogenesis of inflammation, and thus lysine may serve an anti-inflammatory
role (15) by reducing pro-inflammatory cytokines (24). These clinical results suggest that
lysine appears highly suppressive of viral replication, and if these results are confirmed
by further studies, lysine should significantly flatten the curve, reduce mortality and
hospital bed utilization while we await a curative vaccine or vaccines, ideally one with
universal application across the entire Coronavirus group.        
It might be that the combination of suppressive lysine and vaccination is superior to either
alone. There may be places in the world where even inexpensive lysine is unaffordable, but
high lysine foods combined with arginine restriction might still serve the purpose. Our hope
is that these findings will encourage those in a position to perform follow-up studies to do
so, hopefully confirming its usefulness, and further refining our understanding of optimal
dosage, mechanisms, routes of administration and how to maximize the efficacy of this
Cautionary note: Long term asymptomatic (over 1 month) and medically fragile patients
should exercise caution and use low dose lysine for the initial days and incrementally
raise their dose 500 mg every 4 to 5 days, until reaching 2500 mg daily and evaluate.
Higher doses have been used, but the concern is that doses higher than 3000 mg could
result in occult clots embolizing. No coffee, exercise, marijuana, or arginine rich foods
during treatment is included in the recommended protocol. Lysine has been reported to
nearly double serum zinc levels without supplementation. (16) Zinc and calcium should
not be given with lysine since lysine also raises calcium levels. (22) Patients on
pacemakers should be under close clinical observation since lysine might increase
cardiac output (21) and increases pulmonary resistance. (14) Clinicians who are
interested in more details may contact us for additional information at Bio-Virus
Research +1(775) 742 8811,        
Bio-Virus Research Inc.
5774 Tappan Dr.
Reno, Nevada, USA
+1(775) 742-8811
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Objective This observational study aimed to determine optimal timing of interleukin-6 receptor inhibitors (IL6ri) administration for Coronavirus disease 2019 (Covid-19). Methods Patients with Covid-19 were given an IL6ri (sarilumab or tocilizumab) based on iteratively reviewed guidelines. IL6ri were initially reserved for critically ill patients, but after review, treatment was liberalized to patients with lower oxygen requirements. Patients were divided into 2 groups: those requiring ≤ 45% fraction of inspired oxygen (FiO2) (termed stage IIB) and those requiring >45% FiO2 (termed stage III) at the time of IL6ri administration. Main outcomes were all-cause mortality, discharge alive from hospital, and extubation. Results 255 Covid-19 patients were treated with IL6ri (149 stage IIB and 106 stage III). Patients treated in stage IIB had lower mortality than the stage III group (adjusted hazard ratio [aHR]: 0.24; 95% confidence interval [CI] 0.08-0.74). Overall, 218 (85.5%) patients were discharged alive. Patients treated in stage IIB were more likely to be discharged (aHR: 1.43; 95% CI 1.06 – 1.93) and were less likely to be intubated (HR: 0.43; 95% CI: 0.24-0.79). Conclusions IL6ri administration prior to greater than 45% FiO2 requirement was associated with improved Covid-19 outcomes. This can guide clinical management pending results from randomized control trials.
Full-text available
The aim of this study was to investigate the effects of lysine restriction on inflammatory responses in piglets. 38 male piglets with similar body weight of 9.62 kg were randomly divided into control group (basal diet) and lysine-restricted group (diet containing 70% lysine of the control diet). The results showed that lysine restriction increased the serum concentration of IgG an IgM. Piglets fed the lysine-restricted diet exhibited overexpression of interleukin-8 (IL-8) in the kidney (P < 0.05) and IL-6 and IL-4 in the spleen (P < 0.05). The mRNA abundances of IL-4 in the kidney (P < 0.05) and IL-10 in the liver (P < 0.05) were significantly lower in the lysine-restricted group compared with the control group. Meanwhile, lysine restriction increased the mRNA level of Tlr8 in the kidney (P < 0.05) but decreased the mRNA level of Tlr8 in the liver (P < 0.05). Finally, lysine restriction markedly enhanced extracellular signal regulated kinases 1/2 (ERK1/2) phosphorylation in the kidney and liver and nuclear transcription factor kappa B (NF-κB) was activated in the liver and spleen in response to dietary lysine restriction. In conclusion, lysine restriction affected inflammatory responses in the kidney, liver, and spleen via mediating serum antibody volume, inflammatory cytokines, Tlrs system, and ERK1/2 and NF-κB signals in piglets.
Full-text available
Coronaviruses (CoV) belong to the large family Coronaviridae within the order of Nidovirales. Among them, several human pathogenic strains (HCoV) are known to mainly cause respiratory diseases. While most strains contribute to common cold-like illnesses others lead to severe infections. Most prominent representatives are SARS-CoV and MERS-CoV, which can lead to fatal infections with around 10% and 39% mortality, respectively. This resulted in 8098 casualties in the 2002/2003 SARS-CoV outbreak and in 1806 documented human infections (September 2016) during the recent ongoing MERS-CoV outbreak in Saudi Arabia. Currently patients receive treatment focusing on the symptoms connected to the disease rather than addressing the virus as the cause. Therefore, additional treatment options are urgently needed which would ideally be widely available and show a broad affectivity against different human CoVs. Here we show that D, L-lysine acetylsalicylate + glycine sold as " Asprin i.v. 500mg® " (LASAG), which is an approved drug inter alia in the treatment of acute pain, migraine and fever, impairs propagation of different CoV including the highly-pathogenic MERS-CoV in vitro. We demonstrate that the LASAG-dependent impact on virus-induced NF-κB activity coincides with (i) reduced viral titres, (ii) decreased viral protein accumulation and viral RNA synthesis and (iii) impaired formation of viral replication transcription complexes.
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The type II transmembrane serine proteases TMPRSS2 and HAT can cleave and activate the spike-protein (S) of the severe acute respiratory syndrome coronavirus (SARS-CoV) for membrane fusion. In addition, these proteases cleave the viral receptor, the carboxypeptidase angiotensin-converting enzyme 2 (ACE2), and it was proposed that ACE2 cleavage augments viral infectivity. However, no mechanistic insights into this process were obtained and the relevance of ACE2 cleavage for SARS-S activation has not been determined. Here, we show that arginine and lysine residues within ACE2 amino acids 697 - 716 are essential for cleavage by TMPRSS2 and HAT and that ACE2 processing is required for augmentation of SARS-S-driven entry by these proteases. In contrast, ACE2 cleavage was dispensable for activation of the viral S protein. Expression of TMPRSS2 increased cellular uptake of soluble SARS-S, suggesting that protease-dependent augmentation of viral entry might be due to increased uptake of virions into target cells. Finally, TMPRSS2 was found to compete with the metalloprotease ADAM17 for ACE2 processing but only cleavage by TMPRSS2 resulted in augmented SARS-S-driven entry. Collectively, our results in conjunction with previous studies indicate that TMPRSS2 and potentially related proteases promote SARS-CoV entry by two separate mechanisms: ACE2 cleavage, which might promote viral uptake, and SARS-S cleavage, which activates the S protein for membrane fusion. These observations have interesting implications for the development of novel therapeutics. In addition, they should spur efforts to determine whether receptor cleavage promotes entry of other coronaviruses, which use peptidases as entry receptors.
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Lysine appears to suppress the clinical manifestations of herpesvirus infection. 45 patients with frequently recurring herpes infection were given 312-1,200 mg of lysine daily in single or multiple doses. The clinical results demonstrated a beneficial effect from supplementary lysine in accelerating recovery from herpes simplex infection and suppressing recurrence. Tissue culture studies have demonstrated an enhancing effect on viral replication when the amino acid ratio of arginine to lysine favors arginine. The opposite, preponderance of lysine to arginine, suppresses viral replication and inhibits cytopathogenicity of herpes simplex virus. The codons characterizing herpes simplex DNA apparently specify production of viral capsids at the expense of host cell histones.
Historically, the first described effect of an angiotensin converting enzyme (ACE) inhibitor was an increased activity of bradykinin, one of the substrates of ACE. However, in the subsequent years, molecular models describing the mechanism of action of ACE inhibitors in decreasing blood pressure and cardiovascular risk have focused mostly on the renin-angiotensin system. Nonetheless, over the last 20 years, the importance of bradykinin in regulating vasodilation, natriuresis, oxidative stress, fibrinolysis, inflammation, and apoptosis has become clearer. The affinity of ACE appears to be higher for bradykinin than for angiotensin I, thereby suggesting that ACE inhibitors may be more effective inhibitors of bradykinin degradation than of angiotensin II production. Data describing the effect of ACE inhibition on bradykinin signaling support the hypothesis that the most cardioprotective benefits attributed to ACE inhibition may be due to increased bradykinin signaling rather than to decreased angiotensin II signaling, especially when high dosages of ACE inhibitors are considered. In particular, modulation of bradykinin in the endothelium appears to be a major target of ACE inhibition. These new mechanistic concepts may lead to further development of strategies enhancing the bradykinin signaling.
Background: Tuberculosis stills off be found coincides by malnutrition’s condition, which is deficiency among macro and micro nutrient. In the normal circumstances nutrient can be sufficed from knock about food, but in poverty condition and chronic disease, not all nutrient component can be accomplished. So that it’s required to the nutrient supplements substance in order to that nutrient requirement can be accomplished, either in macronutrient or micronutrient. Objective: We studied the immune cellullar’s response (total of TCD4 and the level of INF-γ) on pulmonary tuberculosis patient through supplements zinc, lysine and vitamin A. Methods: In a double-blind randomized community trial, new sputum smear positive pulmonary tuberculosis patients were assigned randomly to zinc+lysine, zinc+lysine+vitamin A, and placebo. Patients examined albumin, retinol and saliva zinc level, CD4 and IFN-γ level before treatment and after 2 months of treatment. Results: The result of the observation shows that giving zinc supplement, lysine, and vitamin A. which is done every day on pulmonary tuberculosis patient up to 2 months can increase the amount of TCD4 as meant (p = 0,040; = 0,050), and IFN- γ rate is increases as meant (p = 0,036; = 0,050). Conclusion: This study has found that supplementation of zinc, lysine, and vitamin A for 2 months can increase total TCD4 and the levels of IFN- γ in pulmonary tuberculosis patients.
The complex of polyriboinosinic-polyribocytidylic (poly(I).poly(C)) with poly-L-lysine in 0.5% carboxymethylcellulose (CMC) [poly(ICLC)] has proven to be an effective interferon inducer in primates, including man. Since no mechanism is known by which the body can degrade CMC, a new complex of lower molecular weight, which contains poly I.poly C complexed with poly-L-lysine [poly(ICL)] but without CMC, was developed. This compound is slightly more resistant than poly(ICLC) to hydrolysis by RNase-A and is also an effective inducer of interferon in nonhuman primates. The new compound without CMC is also less toxic in mice than is poly(ICLC) as indicated by LD50.
We studied the effects of L-lysine in cardiac preparations of mice and men. Of note, L-lysine increased force of contraction in a concentration- and time-dependent manner in isolated electrically paced left atrium of mouse and in human right atrium. It further increased heart rate and left ventricular pressure in the isolated perfused mouse heart. In isolated adult mouse cardiomyocytes, the contractility as assessed by edge detection was increased as well as the Ca(2+) transients after electrically pacing by field stimulation. However, using the patch clamp technique, no effect of L-lysine on action potential duration from a constant holding potential or on current through L-type calcium channels could be observed. However, L-lysine led to a depolarization of unclamped cells. Furthermore, effects of L-lysine were stereospecific, as they were not elicited by D-lysine. The inotropic effects of L-lysine were not abrogated by additionally applied L-ornithine or L-arginine (known inhibitors of lysine transport). However, L-lysine (5 mM) shifted the concentration-response curve for a positive inotropic effect of 5-hydroxytryptamine (5-HT; serotonin) in atrium of transgenic mice (with cardiac specific overexpression of 5-HT(4) receptors) to higher concentrations. In summary, we describe a novel positive inotropic effect of an essential amino acid, L-lysine, in the mammalian heart. One might speculate that L-lysine treatment under certain conditions could sustain cardiac performance. Moreover, L-lysine is able to block, at least in part, cardiac 5-HT(4) receptors.