Virtual screening of natural products inspired in-house library to discover potential lead molecules against the SARS-CoV-2 main protease.

SARS-CoV-2, a new coronavirus emerged in 2019, causing a global healthcare epidemic. Although a variety of drug targets have been identified as potential antiviral therapies, and effective candidate against SARS-CoV-2 remains elusive. One of the most promising targets for combating COVID-19 is SARS-CoV-2 Main protease (Mpro, a protein responsible for viral replication. In this work, an in-house curated library was thoroughly evaluated for druggability against Mpro. We identified four ligands (FG, Q5, P5, and PJ4) as potential inhibitors based on docking scores, predicted binding energies (MMGBSA), in silico ADME, and RMSD trajectory analysis. Among the selected ligands, FG, a natural product from Andrographis nallamalayana, exhibited the highest binding energy of -10.31 kcal/mol close to the docking score of clinical candidates Boceprevir and GC376. Other ligands (P5, natural product from cardiospermum halicacabum and two synthetic molecules Q5 and PJ4) have shown comparable docking scores ranging -7.65 kcal/mol to -7.18 kcal/mol. Interestingly, we found all four top ligands had Pi bond interaction with the main amino acid residues HIS41 and CYS145 (catalytic dyad), H-bonding interactions with GLU166, ARG188, and GLN189, and hydrophobic interactions with MET49 and MET165 in the binding site of Mpro. According to the ADME analysis, Q5 and P5 are within the acceptable range of drug likeliness, compared to FG and PJ4. The interaction stability of the lead molecules with viral protease was verified using replicated MD simulations. Thus, the present study opens up the opportunity of developing drug candidates targeting SARS-CoV-2 main protease (Mpro) to mitigate the disease.Communicated by Ramaswamy H. Sarma.

Holanamine, a Steroidal Alkaloid from the Bark of Holarrhena pubescens Wall. ex G. Don Inhibits the Growth of Leishmania donovani by Targeting DNA Topoisomerase 1B.

Leishmaniasis is a group of neglected tropical diseases (NTDs) caused by about 20 species of obligate intracellular protozoan parasites of the genus Leishmania, which occurs in cutaneous, mucocutaneous, and visceral forms. Many researchers have sought to utilize natural products for novel and effective treatments to combat many infectious diseases, including leishmaniasis. Holarrhena pubescens Wall. ex G. Don (Apocynaceae) bark is a rich source of bioactive steroidal alkaloids. The total alkaloidal extract (IC50 6.12 ± 0.117 µg/mL), and the isolated alkaloid, holanamine, showed significant antileishmanial activity (IC50 2.66 ± 0.112 µM against AG83 and 3.80 ± 0.126 µM against BHU-575) against the Leishmania donovani parasite, better than miltefosine (IC50 19.61 ± 0.093 µM against AG83 and 23.20 ± 0.094 µM against BHU-575). Holanamine inhibited the L. donovani topoisomerase 1B (LdToP1B) in a non-competitive manner (IC50 2.81 ± 0.105 µM), indicating that it interacts with the free enzyme and enzyme-DNA complex without inhibiting human topoisomerase. Hydrogen bonding and hydrophobic interactions of holanamine with the N-terminal and hinge region of the large subunit of LTop1B is responsible for its potent antileishmanial activity, as shown by docking studies. Treatment with holanamine causes apoptotic-like cell death by generating cellular and mitochondrial reactive oxygen species, disrupting the mitochondrial membrane potential and inducing ultrastructural alterations in the promastigotes. Holanamine effectively clears intracellular amastigotes but minimally affects host macrophages with no significant cytotoxicity in HEK 293 and L929 cell lines. Thus, our studies show that holanamine can further be used to develop effective antileishmanial agents against evolving drug-resistant parasites.

Biocompatible carboxymethyl chitosan-modified glass ionomer cement with enhanced mechanical and anti-bacterial properties.

Due to the potential adverse effects of conventional dental cements, the demand for biocompatible cements have grown tremendously in the field of dentistry. In this respect, Glass ionomer cements (GICs) are being developed by different researchers. However, low mechanical strength of GIC make them unsuitable for application in high-stress areas. Thus, numerous initiatives to improve mechanical performance have been attempted till date including incorporation of reinforcing fillers. Novelty of the study lies in using carboxymethyl chitosan (CMC) to develop a biocompatible dental cement (DC/CMC-m-GP), which would have enhanced mechanical strength due to greater interaction of CMC with the particles of GIC and better cyto-compatibility due to its cell-proliferation activity. The mechanical strength, acid erosion and fluoride release of DC/CMC-m-GP were studied and compared with control dental cement (DC/Control). DC/CMC-m-GP shows compressive strength of 157.45 M Pa and flexural strength of 18.76 M Pa which was higher as compared to DC/Control. The morphology of the GICs were studied through FESEM. Anti-microbial activity of DC/CMC-m-GP was studied by Agar disc-diffusion method and biofilm assay against S. mutans, which shows that DC/CMC-m-GP inhibits bacterial adhesion on its surface. MTT assay infers that DC/CMC-m-GP was non-cytotoxic and did not affect the cell viability significantly.

Plasma polymerized functional supermagnetic Fe3O4 nanostructured templates for laccase immobilization: A robust catalytic system for bio-inspired dye degradation.

Fe3O4 magnetic nanoparticles, synthesized using co-precipitation method, were epoxy functionalized via plasma polymerization of 2,3-epoxypropylmethacrylate (EPMA) precursor. The EPMA-functionalized Fe3O4 nanoparticles (EPMA-f-MN) were employed as templates for facile, one-step covalent immobilization of laccase enzyme at room temperature. Samples were rigorously characterized by FTIR, TGA, SEM, TEM, XRD techniques, while Mössbauer spectroscopy (MöS) and vibrating sample magnetometry (VSM) confirmed the supermagnetic nature of Fe3O4 nanoparticles. Activities of free and immobilized laccase (ImLac) were assayed by spectrophotometrically monitoring the enzymatic reduction of substrate 2,2-azino-bis(3-ethylthiazoline-6-sulfonate) (ABTS) at 420 nm, corresponding to the λmax of ABTS.+. In addition to possessing higher thermal stability and a broader pH tolerance window compared to free laccase, the supermagnetic property of the Fe3O4 renders the ImLac system conveniently recoverable and recyclable. Practical applicability of ImLac towards catalytic degradation of industrial dyes was also ably demonstrated using Acid Blue 193 (AB 193) as a commercially used model textile dye, which belongs to the family of azo dyes. Over 95% degradation of the dye was achieved within a period of 4 hours. ImLac could be used for more than 10 dye degradation cycles with >90 % of retention in enzyme activity.

Coronavirus Disease-19 and Re-infection: Unknown of the Unknown.

Coronavirus disease has caused seven million infections worldwide, of which, 3.1 million individuals have recovered. Though, most individuals develop antibodies, whether these antibodies result in clinical improvement/immunity from future infection is not known. It is also not known about durability of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). No human re-infection with SARS-CoV-2 has been confirmed to date, although a few case reports have mentioned patients who have tested positive again after recovery from the initial illness. Whether these cases represent a state of carrier or re-infection or reactivation, is not known. Nevertheless, the possibility of re-infection remains a matter of concern and yet another question about SARS-CoV-2 which is still unanswered.

COVID-19 and the Kidneys, Implications and Outcomes.

Coronavirus disease (COVID-19), declared as a pandemic has affected millions of people and caused unprecedented number of death. The disease is caused by a severe acute respiratory syndrome related coronaviruses-2 virus which enters cells by binding with the host angiotensin converting enzyme-2 and CD147 protein. Among COVID-19 patients admitted to a hospital, hypertension, diabetes and obesity are the most common co-morbidities. A majority of COVID-19 hospitalized patients are found to have proteinuria and hematuria which is associated with higher risk of in-hospital mortality. Studies have reported high incidence of acute kidney injury (AKI) among COVID-19 patients admitted to hospital (10 to 43%) and intensive care unit (43-75%). These patients with AKI have much higher need for mechanical ventilation, vasopressor use and critical care. In addition, proportion of patients with AKI who require renal replacement (RRT) therapy is greatly increased. Acute tubular injury, cytokine storm induced systemic inflammatory response, endothelial injury and dysfunction are the main mechanisms of AKI. In addition, direct viral invasion of tubules, lymphocytic infiltration and complement mediated (C5b- 9) related injury is also seen. Mortality risk among patients with AKI and those in need of RRT is greatly amplified. Appropriate timing and choice of RRT for these patients is not well defined but will need to take in account the clinical condition, anticipation of their clinical course and availability of dialysis resources. Risk of AKI and death is also increased among kidney recipients and patients with chronic kidney disease.

Primary retroperitoneal hydatid cyst masquerading as malignancy.

Hydatid cysts, usually found in liver and lungs, are rare to be primarily located in the retroperitoneal region. It may mimic malignant mass and differentiation may be difficult. Surgical exploration in undiagnosed cases may lead to adverse complications. High index of suspicion is crucial, especially in patients from endemic region. Diagnosis can be aided by imaging and serologic testing for Echinococcus IgG. We present a 61-year-old Tibetan female visiting to North America and found to have a complex cystic and solid capsulated right retroperitoneal mass. Echinococcus IgG western blot assay was positive, and the patient was diagnosed to have primary retroperitoneal hydatid cyst.

A comparative assessment of in vitro cytotoxic activity and phytochemical profiling of Andrographis nallamalayana J.L.Ellis and Andrographis paniculata (Burm. f.) Nees using UPLC-QTOF-MS/MS approach.

Andrographis paniculata (Burm. f.) Nees and Andrographis nallamalayana J.L.Ellis have traditionally been used to treat various ailments such as mouth ulcers, intermittent fever, inflammation, snake bite. This study compares the comparative in vitro cytotoxic activity, and phytochemical profiling of methanol extract of A. nallamalayana (ANM) and A. paniculata (APM). UPLC-ESI-QTOF-MS/MS analysis has been performed. The cytotoxic activity of crude methanol extracts were evaluated against three different cancer cell lines (HCT 116, HepG2, and A549 cell line). Both plants' extract exhibited significant cytotoxic activity against tested cell lines in a dose-dependent manner. IC50 of ANM and APM in HCT 116 cell was 11.71 ± 2.48 µg ml-1 and 45.32 ± 0.86 µg ml-1 and in HepG2 cell line was 15.65 ± 2.25 µg ml-1 and 60.32 ± 1.05 µg ml-1 respectively. Cytotoxicity of these two extracts was comparatively similar in A549 cells. ANM induced cytotoxicity involved programmed cell death, externalisation of phosphatidylserine, ROS generation, up-regulation and down-regulation of major apoptotic markers. HRMS analysis of ANM and APM resulted in the identification of 59 and 42 compounds, respectively. Further, using the MS/MS fragmentation approach, 20 compounds, of which 18 compounds were identified for the first time from ANM, which belongs to phenolic acids, flavonoids, and their glycosides. Three known compounds, echioidinin, skullcapflavone I and 5,2',6'-trihydroxy-7-methoxyflavone 2'-O-ß-d-glucopyranoside, were isolated from A. nallamalayana and their crystal structures were reported for the first time. Subsequently, seven major compounds were identified in A. nallamalayana by direct comparison (retention time and UV-spectra) with authentic commercial standards and isolated compounds using HPLC-UV analysis. The cytotoxicity of phytochemicals from both the plants using in silico tools also justify their in vitro cytotoxic activity. It is the first report on the comparative characterisation of phytochemicals present in the methanolic extract of both the species of Andrographis, along with the cytotoxic activity of A. nallamalayana.

Hemoperitoneum After Cardiopulmonary Resuscitation in Peritoneal Dialysis Patients: A Tale of Two Cases.

End-stage renal disease (ESRD) patients are at much higher risk of cardiac arrest as compared to the general population. In the event of a cardiac arrest, cardiopulmonary resuscitation (CPR) is a lifesaving procedure. In fact, the need for CPR among hospitalized ESRD patients is almost 20 times higher than the general population. Complications of CPR include thoracic injuries such as flail chest, rib fractures, pneumothorax, and rarely intra-abdominal complications. Hemoperitoneum is a well-recognized complication among peritoneal dialysis patients but as a complication of CPR is rarely described. Inappropriate CPR technique, hepatic ischemia and venous congestion, platelet dysfunction, and the use of anti-platelet agents can increase the risk of such injury and bleeding. Hemoperitoneum in this setting can be serious with significant complications and may require transition from peritoneal dialysis (PD) to hemodialysis. We report two such PD patients who developed hemoperitoneum as a complication after CPR and their course.

Anticoagulation in Patients with End-Stage Renal Disease and Atrial Fibrillation: Confusion, Concerns and Consequences.

End-stage renal disease (ESRD) patients have a higher prevalence of diabetes mellitus, hypertension, congestive heart failure and advanced age, along with an increased incidence of non-valvular atrial fibrillation (AF), thereby increasing the risk for cerebrovascular accidents. Systemic anticoagulation is therefore recommended in patients with ESRD with AF to reduce the risk and complications from thromboembolism. Paradoxically, these patients are at an increased risk of bleeding due to great degree of platelet dysfunction and impaired interaction between platelet and endothelium. Currently, CHA2DS2-VASc and Hypertension, Abnormal liver/kidney function, Stroke, Bleeding, Labile INR, Elderly, Drugs or alcohol (HAS-BLED) are the recommended models for stroke risk stratification and bleeding risk assessment in patients with AF. There is conflicting data regarding benefits and risks of medications such as antiplatelet agents, warfarin and direct oral anticoagulants in ESRD patients with AF. Moreover, there is no randomized controlled trial data to guide the clinical decision making. Hence, a multi-disciplinary approach with annual re-evaluation of treatment goals and risk-benefit assessment has been recommended. In this article, we review the current recommendations with risks and benefits of anticoagulation in patients with ESRD with AF.

Radiation grafted cellulose fabric as reusable anionic adsorbent: A novel strategy for potential large-scale dye wastewater remediation.

A low cost, cellulose based anionic adsorbent has been synthesized at room temperature by single step gamma radiation induced grafting of 4-vinylbenzenesulfonic acid sodium salt (VBSA) onto cellulose using water as solvent. Grafting parameters, namely, radiation dose, monomer concentration, volume/weight ratio, were studied to optimize the radiation grafting process. Poly(VBSA) grafted cellulose (PVBSA-g-cellulose) samples were characterized by grafting yield estimation, Elemental analysis, FTIR, TGA and SEM. The radiation grafted adsorbent was tested for textile dyes removal from aqueous solutions, in batch and continuous flow column operation mode, using Basic Red-29 (BR-29) dye as a model textile dye. Adsorbent with 25% grafting yield exhibited an adsorption capacity of 320 mg.g-1, which was corroborated by the equilibrium adsorption and kinetic studies. The adsorbent was regenerated and demonstrated to be reusable for multiple cycles with minimal attrition losses. The process was successfully upscaled and demonstrated at a semi pilot scale treatment.

Intradialytic acid-base changes and organic anion production during high versus low bicarbonate hemodialysis.

The use of high dialysate bicarbonate for hemodialysis in end-stage renal disease is associated with increased mortality, but potential physiological mediators are poorly understood. Alkalinization due to high dialysate bicarbonate may stimulate organic acid generation, which could lead to poor outcomes. Using measurements of ß-hydroxybutyrate (BHB) and lactate, we quantified organic anion (OA) balance in two single-arm studies comparing high and low bicarbonate prescriptions. In study 1 (n = 10), patients became alkalemic using 37 meq/L dialysate bicarbonate; in contrast, with the use of 27 meq/L dialysate, net bicarbonate loss occurred and blood bicarbonate decreased. Total OA losses were not higher with 37 meq/L dialysate bicarbonate (50.9 vs. 49.1 meq using 27 meq/L, P = 0.66); serum BHB increased in both treatments similarly (P = 0.27); and blood lactate was only slightly higher with the use of 37 meq/L dialysate (P = 0.048), differing by 0.2 meq/L at the end of hemodialysis. In study 2 (n = 7), patients achieved steady state on two bicarbonate prescriptions: they were significantly more acidemic when dialyzed against a 30 meq/L bicarbonate dialysate compared with 35 meq/L and, as in study 1, became alkalemic when dialyzed against the higher bicarbonate dialysate. OA losses were similar to those in study 1 and again did not differ between treatments (38.9 vs. 43.5 meq, P = 0.42). Finally, free fatty acid levels increased throughout hemodialysis and correlated with the change in serum BHB (r = 0.81, P < 0.001), implicating upregulation of lipolysis as the mechanism for increased ketone production. In conclusion, lowering dialysate bicarbonate does not meaningfully reduce organic acid generation during hemodialysis or modify organic anion losses into dialysate.

Choice of dialysis modality prior to kidney transplantation: Does it matter?

The population of patients with end stage renal disease (ESRD) is increasing, lengthening waiting lists for kidney transplantation. Majority of the patients are not able to receive a kidney transplant in timely manner even though it is well established that patient survival and quality of life after kidney transplantation is far better when compared to being on dialysis. A large number of patients who desire a kidney transplant ultimately end up needing some form of dialysis therapy. Most of incident ESRD patients choose hemodialysis (HD) over peritoneal dialysis (PD) as the modality of choice in the United States, even though studies have favored PD as a better choice of pre-transplant dialysis modality than HD. PD is largely underutilized in the United States due to variety of reasons. As a part of the decision making process, patients are often educated how the choice regarding modality of dialysis would fit into their life but it is not clear and not usually discussed, how it can affect eventual kidney transplantation in the future. In this article we would like to discuss ESRD demographics and outcomes, modality of dialysis and kidney transplant related events. We have summarized the data comparing PD and HD as the modality of dialysis and its impact on allograft and recipient outcomes after kidney transplantation.

Mitigation of Cr(VI) toxicity using Pd-nanoparticles immobilized catalytic reactor (Pd-NICaR) fabricated via plasma and gamma radiation.

Catalytic reduction of Cr(VI) to less toxic Cr(III) form using metal nanoparticles is one of the novel approaches adopted to deal with Cr toxicity. In this work, we report the fabrication of a facile, reusable, and robust Pd nanoparticles-immobilized catalytic reactor (Pd-NICaR) system using green, environment-friendly gamma radiolytic, and plasma polymerization processes. A room temperature, RF-powered plasma polymerization process was employed to functionalize a polyethylene-polypropylene (PE-PP) non-woven matrix with epoxy group containing monomer 2,3-epoxypropyl methacrylate (EPMA). EPMA-functionalized PE-PP (EPMA-f-PE-PP) substrate was subsequently used as a template for in situ generation and immobilization of Pd NPs via gamma radiolytic route. The samples were characterized using FTIR, SEM, XPS, and XRF techniques. The catalytic efficacy of Pd-NICaR towards Cr(VI) reduction, in the presence of formic acid (FA) as a reductant, was investigated spectrophotometrically, and reaction parameters were optimized at reaction temperature of 50 °C and [FA]/[Cr(VI)] = 680 to achieve catalytic reduction efficiency of 99.7% within 10 min in batch process. The system showed excellent reusability (~ 20 cycles) and storage stability (> 30 days) without substantial loss (~ 11%) of activity. Practical applicability of the robust catalytic system towards Cr(VI) toxicity mitigation was established in continuous flow mode using a fixed-bed column reactor.

Vascular access placement in patients with chronic kidney disease Stages 4 and 5 attending an inner city nephrology clinic: a cohort study and survey of providers.

BACKGROUND: The majority of incident hemodialysis (HD) patients initiate dialysis via catheters. We sought to identify factors associated with initiating hemodialysis with a functioning arterio-venous (AV) access. METHODS: We conducted a retrospective chart review of all adult patients, age >18 years seeing a nephrologist with a diagnosis of CKD stage 4 or 5 during the study period between 06/01/2011 and 08/31/2013 to evaluate the placement of an AV access, initiation of dialysis and we conducted a survey of providers about the process. RESULTS: The 221 patients (56% female) in the study had median age of 66 years (interquartile range (IQR), 57-75) and were followed for a median of 1.26 years (IQR 0.6-1.68). At study entry, 81%had CKD stage 4 and 19% had CKD stage 5. By the end of study, 48 patients had initiated dialysis. Thirty-four of the patients started dialysis with a catheter (1 failed and 10 maturing AVFs), 9 with an AVF and 5 with an AVG. During the study period, 61 total AV accesses were placed (54 AVF and 7 AVG). A higher urinary protein/ creatinine ratio and a lower eGFR were associated with AV access placement and dialysis initiation. A greater number of nephrology visits were associated with AV access creation but not dialysis initiation. Hospitalizations and hospitalizations with an episode of acute kidney injury (AKI) were strongly associated with dialysis initiation (odds ratio (OR) 13.0 (95% confidence interval (CI) 2.3 to 73.3, p-value = 0.004) and OR 6.6 (95% CI 1.9 to 22.8, p-value = 0.003)). CONCLUSIONS: More frequent nephrology clinic visits for patients with a recent hospitalization may improve rates of placement of an AV access. A hospitalization with AKI is strongly associated with the need for dialysis initiation. Nephrologists may not be referring the correct patients to get an AV access surgery.

Cellulose based cationic adsorbent fabricated via radiation grafting process for treatment of dyes waste water.

A cationized adsorbent was prepared from cellulosic cotton fabric waste via a single step-green-radiation grafting process using gamma radiation source, wherein poly[2-(methacryloyloxy) ethyl]trimethylammonium chloride (PMAETC) was covalently attached to cotton cellulose substrate. Radiation grafted (PMAETC-g-cellulose) adsorbent was investigated for removal of acid dyes from aqueous solutions using two model dyes: Acid Blue 25 (AB25) and Acid Blue 74 (AB74). The equilibrium adsorption data was analyzed by Langmuir and Freundlich isotherms, whereas kinetic data was analyzed by pseudo first order, pseudo second order, intra particle diffusion and Boyd's models. The PMAETC-g-cellulose adsorbent with 25% grafting yield exhibited equilibrium adsorption capacities of ∼ 540.0mg/g and ∼ 340.0mg/g for AB25 and AB74, respectively. Linear and nonlinear fitting of adsorption data suggested that the equilibrium adsorption process followed Langmuir adsorption isotherm model, whereas, the kinetic adsorption process followed pseudo-second order model. The multi-linearities observed in the intra-particle kinetic plots suggested that the intraparticle diffusion was not the only rate-controlling process in the adsorption of acid dyes on the adsorbent, which was further supported by Boyd's model. The adsorbent could be regenerated by eluting the adsorbed dye from the adsorbent and could be repeatedly used.

Cocaine and kidney injury: a kaleidoscope of pathology.

Cocaine is abused worldwide as a recreational drug. It is a potent activator of the sympathetic nervous system leading to intense vasoconstriction, endothelial dysfunction, oxidative stress, platelet activation and decrease in prostaglandins E2 and prostacyclin. Cocaine can lead to widespread systemic adverse effects such as stroke, myocardial infarction, arterial dissection, vascular thrombosis and rhabdomyolysis. In human and rat kidneys, cocaine has been associated with glomerular, tubular, vascular and interstitial injury. It is not uncommon to diagnose cocaine-related acute kidney injury (AKI), malignant hypertension and chronic kidney disease. Cocaine abuse can lead to AKI by rhabdomyolysis, vasculitis, infarction, thrombotic microangiopathy and malignant hypertension. It is reported that 50-60% of people who use both cocaine and heroin are at increased risk of HIV, hepatitis and additional risk factors that can cause kidney diseases. While acute interstitial nephritis (AIN) is a known cause of AKI, an association of AIN with cocaine is unusual and seldom reported. We describe a patient with diabetes mellitus, hypertension and chronic hepatitis C, who presented with AKI. Urine toxicology was positive for cocaine and a kidney biopsy was consistent with AIN. Illicit drugs such as cocaine or contaminants may have caused AIN in this case and should be considered in the differential diagnosis of causes of AKI in a patient with substance abuse. We review the many ways that cocaine adversely impacts on kidney function.

Role of vitamin D receptor activation in racial disparities in kidney disease outcomes.

African Americans have lower 25-hydroxyvitamin D (25(OH)D) levels compared with whites. African Americans also have a higher risk of developing albuminuria and end-stage renal disease but a lower risk of death once they commence hemodialysis compared with whites. Vitamin D levels have been associated with multiple outcomes including albuminuria, progression to end-stage renal disease, and all-cause and cardiovascular mortality. In this review, we examine the evidence linking 25(OH)D to outcomes and the possibility that differential 25(OH)D may explain certain racial differences in outcomes.

Mouse heart rate in a human: diagnostic mystery of an extreme tachyarrhythmia.

We report telemetry recording of an extreme non-fatal tachyarrhythmia noted in a hospitalized quadriplegic male with history of atrial fibrillation where the average ventricular conduction rate was found to be about 600 beats per minute and was associated with transient syncope. A medical literature review suggests that the fastest human ventricular conduction rate reported to date in a tachyarrhythmia is 480 beats per minute. We therefore report the fastest human heart rate noted in a tachyarrhythmia and the most probable mechanism of this arrhythmia being a rapid atrial fibrillation with 1:1 conduction in the setting of probable co-existing multiple bypass tracts.