Recurrence in isolated distal DVT after anticoagulation: a systematic review and meta-analysis of axial and muscular venous thrombosis.

OBJECTIVE: To identify recurrent venous thromboembolism (VTE) after discontinuation of anticoagulation in patients with isolated distal deep vein thrombosis based on its anatomic localization (axial or muscular veins). METHODS: Data were sourced from PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases in the time period up to October 2023. The study followed PRISMA guidelines using a registered protocol (CRD42023443029). Studies reporting recurrent VTE in patients with axial or muscular DVT were included in the analysis. RESULTS: Five studies with a total of 1,403 participants were evaluated. The results showed a pooled odds ratio of 1.12 (95% confidence interval 0.77-1.63) between axial and muscular DVT. Heterogeneity was low (I2 = 0%, p = 0.91) and there was no significant difference in the rate of recurrent VTE between axial and muscular DVT in each subgroup. CONCLUSIONS: Muscular and axial DVT showed comparable recurrent VTE rates after anticoagulation. However, uncertainties regarding the possibility of recurrence affecting the popliteal vein or resulting in pulmonary embolism following muscular DVT anticoagulation persisted. Randomized trials in patients with isolated distal DVT are still needed to clarify its prognosis for different anatomical thrombus locations.

Validation of a pulmonary embolism risk assessment model in gynecological inpatients : Clinical trial: A single-center, retrospective study.

OBJECTIVE: To compare the predictive efficacy of the PADUA and Caprini models for pulmonary embolism (PE) in gynecological inpatients, analyze the risk factors for PE, and validate whether both models can effectively predict mortality rates. METHODS: A total of 355 gynecological inpatients who underwent computed tomography pulmonary angiography (CTPA) were included in the retrospective analysis. The comparative assessment of the predictive capabilities for PE between the PADUA and Caprini was carried out using receiver operating characteristic (ROC) curves. Logistic regression analysis was used to identify risk factors associated with PE. Additionally, Kaplan-Meier survival analysis plots were generated to validate the predictive efficacy for mortality rates. RESULTS: Among 355 patients, the PADUA and Caprini demonstrated the area under the curve (AUC) values of 0.757 and 0.756, respectively. There was no statistically significant difference in the AUC between the two models (P = 0.9542). Multivariate logistic analysis revealed immobility (P < 0.001), history of venous thromboembolism (VTE) (P = 0.002), thrombophilia (P < 0.001), hormonal treatment (P = 0.022), and obesity (P = 0.019) as independent risk factors for PE. Kaplan-Meier survival analysis demonstrated the reliable predictive efficacy of both the Caprini (P = 0.00051) and PADUA (P = 0.00031) for mortality. ROC for the three- and six-month follow-ups suggested that the Caprini model exhibited superior predictive efficacy for mortality. CONCLUSIONS: The PADUA model can serve as a simple and effective tool for stratifying high-risk gynecological inpatients before undergoing CTPA. The Caprini model demonstrated superior predictive efficacy for mortality rates.

Cutaneous Hydrophilic Polymer Embolism: An Important and Overlooked Clinical Entity.

ABSTRACT: Hydrophilic polymer embolism from vascular medical devices is an underrecognized clinical entity that can cause deleterious end-organ ischemia and culminate in mortality. This is concerning as we are in the era where minimally invasive procedures are commonplace. Diagnosis is often made retrospectively after obtaining histopathological tissue samples showing endoluminal, cerebriform, amorphous, anucleate, basophilic, nonrefractile, nonpolarizable foreign body material. We detail 2 more cases of cutaneous hydrophilic polymer embolism to underscore its salient clinicopathological features and increase awareness of this important iatrogenic entity.

Safety and efficacy of stoma site selection in CT-guided percutaneous gastrostomy: a retrospective analysis.

PURPOSE: To compare the safety and efficacy of CPG in the rectus abdominis and intercostal regions. MATERIALS AND METHODS: This retrospective study included 226 patients who underwent CPG at a single center, with the stoma placed in the rectus abdominis or intercostal region. Surgical outcomes and complications, such as pain and infection within 6 months postoperatively, were recorded. RESULTS: The surgical success rate was 100%, and the all-cause mortality rate within 1 month was 0%. An intercostal stoma was placed in 56 patients; a rectus abdominis stoma was placed in 170 patients. The duration of surgery was longer for intercostal stoma placement (37.66 ± 14.63 min) than for rectus abdominis stoma placement (30.26 ± 12.40 min) (P = 0.000). At 1 month postsurgery, the rate of stoma infection was greater in the intercostal group (32.1%) than in the rectus abdominis group (20.6%), but the difference was not significant (P = 0.077). No significant difference was observed in the infection rate between the two groups at 3 or 6 months postsurgery (P > 0.05). Intercostal stoma patients reported higher pain scores during the perioperative period and at 1 month postsurgery (P = 0.000), but pain scores were similar between the two groups at 3 and 6 months postsurgery. The perioperative complication rates for intercostal and rectus abdominis surgery were 1.8% and 5.3%, respectively (P = 0.464), with no significant difference in the incidence of tube dislodgement (P = 0.514). Patient weight improved significantly at 3 and 6 months postoperatively compared to preoperatively (P < 0.05). CONCLUSION: Rectus abdominis and intercostal stomas have similar safety and efficacy. However, intercostal stomas may result in greater short-term patient discomfort.

Unconditional and Robust Quantum Metrological Advantage beyond N00N States.

Quantum metrology employs quantum resources to enhance the measurement sensitivity beyond that can be achieved classically. While multiphoton entangled N00N states can in principle beat the shot-noise limit and reach the Heisenberg limit, high N00N states are difficult to prepare and fragile to photon loss which hinders them from reaching unconditional quantum metrological advantages. Here, we combine the idea of unconventional nonlinear interferometers and stimulated emission of squeezed light, previously developed for the photonic quantum computer Jiuzhang, to propose and realize a new scheme that achieves a scalable, unconditional, and robust quantum metrological advantage. We observe a 5.8(1)-fold enhancement above the shot-noise limit in the Fisher information extracted per photon, without discounting for photon loss and imperfections, which outperforms ideal 5-N00N states. The Heisenberg-limited scaling, the robustness to external photon loss, and the ease-of-use of our method make it applicable in practical quantum metrology at a low photon flux regime.

Solving Graph Problems Using Gaussian Boson Sampling.

Gaussian boson sampling (GBS) is not only a feasible protocol for demonstrating quantum computational advantage, but also mathematically associated with certain graph-related and quantum chemistry problems. In particular, it is proposed that the generated samples from the GBS could be harnessed to enhance the classical stochastic algorithms in searching some graph features. Here, we use Jiǔzhang, a noisy intermediate-scale quantum computer, to solve graph problems. The samples are generated from a 144-mode fully connected photonic processor, with photon click up to 80 in the quantum computational advantage regime. We investigate the open question of whether the GBS enhancement over the classical stochastic algorithms persists-and how it scales-with an increasing system size on noisy quantum devices in the computationally interesting regime. We experimentally observe the presence of GBS enhancement with a large photon-click number and a robustness of the enhancement under certain noise. Our work is a step toward testing real-world problems using the existing noisy intermediate-scale quantum computers and hopes to stimulate the development of more efficient classical and quantum-inspired algorithms.

Gaussian Boson Sampling with Pseudo-Photon-Number-Resolving Detectors and Quantum Computational Advantage.

We report new Gaussian boson sampling experiments with pseudo-photon-number-resolving detection, which register up to 255 photon-click events. We consider partial photon distinguishability and develop a more complete model for the characterization of the noisy Gaussian boson sampling. In the quantum computational advantage regime, we use Bayesian tests and correlation function analysis to validate the samples against all current classical spoofing mockups. Estimating with the best classical algorithms to date, generating a single ideal sample from the same distribution on the supercomputer Frontier would take ∼600 yr using exact methods, whereas our quantum computer, Jiǔzhang 3.0, takes only 1.27 µs to produce a sample. Generating the hardest sample from the experiment using an exact algorithm would take Frontier∼3.1×10^{10} yr.

Clinical Outcomes of Drug-Coated Balloon Angioplasty in Peripheral Artery Disease Patients With End-Stage Renal Disease.

PURPOSE: The objective was to determine the effectiveness and safety of paclitaxel-coated balloon angioplasty in hemodialysis patients with diabetic nephropathy (DN). MATERIALS AND METHODS: The outcomes of end-stage renal disease (ESRD) patients with peripheral artery disease (PAD) and treated with drug-coated balloon (DCB) angioplasty were retrospectively evaluated. The effectiveness outcomes were clinical improvement of the Rutherford classification and target lesion revascularization (TLR). Safety outcomes were all-cause mortality and amputation. RESULTS: Ninety-seven patients were treated with DCB angioplasty between December 2018 and December 2020. 87 (63.8±10.1 years) achieved technical success. Most patients had a Rutherford classification of at least grade 4. The mean lesion length was 169.8±73.8 mm, almost all had arterial calcification, and 31.0% had annular calcification. Wounds were present in 73.6% of the target limbs. The mean follow-up in this cohort was 13.4±7.4 months. The wound healing rate was 61.5% at the 12-month follow-up. All-cause mortality during 12 months of follow-up was 35.6%, amputation-free survival was 58.6%, and TLR was observed in 13 (15.3%) patients. At 3 and 12 months of follow-up, the Rutherford grade significantly improved (p<0.001). The Cox proportional hazards model revealed that wounds (hazard ratio [HR]=1.404, p=0.023) and annular calcification (HR=2.076, p=0.031) were independent predictors of amputation-free survival. CONCLUSIONS: Drug-coated balloon angioplasty in ESRD patients was effective and safe over the medium term. Wounds and annular calcification were independent predictors of amputation-free survival. CLINICAL IMPACT: The effectiveness of DCB angioplasty in ESRD patients and the factors affecting major outcome prognosis in this population remain limited. This study contributes valuable insights into the effectiveness and safety of paclitaxel-coated balloon angioplasty for PAD in hemodialysis patients. Medical professionals can now regard DCB angioplasty as a viable treatment. Identifying wound presence and annular calcification as predictors of amputation-free survival equips medical practitioners with a more tailored approach to patient management, potentially resulting in enhanced outcomes and more precise treatment strategies.

Acute iododerma presenting as cryptococcoid neutrophilic dermatosis: A clinicopathological pitfall and interesting findings gleaned from a review of the literature.

Iododerma is an uncommon dermatosis caused by excessive iodine exposure and is associated with significant morbidity and mortality. Because of its heterogenous clinical presentation and variable histopathological findings, which depend on the time the skin biopsy is performed, the diagnosis of iododerma is often delayed. We report a rare case of acute iododerma in a woman with end-stage diabetic nephropathy with antecedent radioiodine contrast exposure, presenting histopathologically as cryptococcoid neutrophilic dermatosis (CND). We underscore important clinicopathological pitfalls to avoid misdiagnosis with similar overlapping entities such as Sweet syndrome, review all published cases of CND and draw novel insights into its associated entities.

AlphaFold2 versus experimental structures: evaluation on G protein-coupled receptors.

As important drug targets, G protein-coupled receptors (GPCRs) play pivotal roles in a wide range of physiological processes. Extensive efforts of structural biology have been made on the study of GPCRs. However, a large portion of GPCR structures remain unsolved due to structural instability. Recently, AlphaFold2 has been developed to predict structure models of many functionally important proteins including all members of the GPCR family. Herein we evaluated the accuracy of GPCR structure models predicted by AlphaFold2. We revealed that AlphaFold2 could capture the overall backbone features of the receptors. However, the predicted models and experimental structures were different in many aspects including the assembly of the extracellular and transmembrane domains, the shape of the ligand-binding pockets, and the conformation of the transducer-binding interfaces. These differences impeded the use of predicted structure models in the functional study and structure-based drug design of GPCRs, which required reliable high-resolution structural information.

143D, a novel selective KRASG12C inhibitor exhibits potent antitumor activity in preclinical models.

The KRASG12C mutant has emerged as an important therapeutic target in recent years. Covalent inhibitors have shown promising antitumor activity against KRASG12C-mutant cancers in the clinic. In this study, a structure-based and focused chemical library analysis was performed, which led to the identification of 143D as a novel, highly potent and selective KRASG12C inhibitor. The antitumor efficacy of 143D in vitro and in vivo was comparable with that of AMG510 and of MRTX849, two well-characterized KRASG12C inhibitors. At low nanomolar concentrations, 143D showed biochemical and cellular potency for inhibiting the effects of the KRASG12C mutation. 143D selectively inhibited cell proliferation and induced G1-phase cell cycle arrest and apoptosis by downregulating KRASG12C-dependent signal transduction. Compared with MRTX849, 143D exhibited a longer half-life and higher maximum concentration (Cmax) and area under the curve (AUC) values in mouse models, as determined by tissue distribution assays. Additionally, 143D crossed the blood‒brain barrier. Treatment with 143D led to the sustained inhibition of KRAS signaling and tumor regression in KRASG12C-mutant tumors. Moreover, 143D combined with EGFR/MEK/ERK signaling inhibitors showed enhanced antitumor activity both in vitro and in vivo. Taken together, our findings indicate that 143D may be a promising drug candidate with favorable pharmaceutical properties for the treatment of cancers harboring the KRASG12C mutation.

Discovery and identification of a novel small molecule BCL-2 inhibitor that binds to the BH4 domain.

The B-cell lymphoma 2 (BCL-2) protein family plays a pivotal role in regulating the apoptosis process. BCL-2, as an antiapoptotic protein in this family, mediates apoptosis resistance and is an ideal target for cell death strategies in cancer therapy. Traditional treatment modalities target BCL-2 by occupying the hydrophobic pocket formed by BCL-2 homology (BH) domains 1-3, while in recent years, the BH4 domain of BCL-2 has also been considered an attractive novel target. Herein, we describe the discovery and identification of DC-B01, a novel BCL-2 inhibitor targeting the BH4 domain, through virtual screening combined with biophysical and biochemical methods. Our results from surface plasmon resonance and cellular thermal shift assay confirmed that the BH4 domain is responsible for the interaction between BCL-2 and DC-B01. As evidenced by further cell-based experiments, DC-B01 induced cell killing in a BCL-2-dependent manner and triggered apoptosis via the mitochondria-mediated pathway. DC-B01 disrupted the BCL-2/c-Myc interaction and consequently suppressed the transcriptional activity of c-Myc. Moreover, DC-B01 inhibited tumor growth in vivo in a BCL­2­dependent manner. Collectively, these results indicate that DC-B01 is a promising BCL-2 BH4 domain inhibitor with the potential for further development.

Discovery and characterization of a novel cGAS covalent inhibitor for the treatment of inflammatory bowel disease.

Cyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor, acts as a nucleotidyl transferase that catalyzes ATP and GTP to form cyclic GMP-AMP (cGAMP) and plays a critical role in innate immunity. Hyperactivation of cGAS-STING signaling contributes to hyperinflammatory responses. Therefore, cGAS is considered a promising target for the treatment of inflammatory diseases. Herein, we report the discovery and identification of several novel types of cGAS inhibitors by pyrophosphatase (PPiase)-coupled activity assays. Among these inhibitors, 1-(1-phenyl-3,4-dihydro-1H-pyrrolo[1,2-a]pyrazin-2-yl)prop-2-yn-1-one (compound 3) displayed the highest potency and selectivity at the cellular level. Compound 3 exhibited better inhibitory activity and pathway selectivity than RU.521, which is a selective cGAS inhibitor with anti-inflammatory effects in vitro and in vivo. Thermostability analysis, nuclear magnetic resonance and isothermal titration calorimetry assays confirmed that compound 3 directly binds to the cGAS protein. Mass spectrometry and mutation analysis revealed that compound 3 covalently binds to Cys419 of cGAS. Notably, compound 3 demonstrated promising therapeutic efficacy in a dextran sulfate sodium (DSS)-induced mouse colitis model. These results collectively suggest that compound 3 will be useful for understanding the biological function of cGAS and has the potential to be further developed for inflammatory disease therapies.

Multi-Type Missing Imputation of Time-Series Power Equipment Monitoring Data Based on Moving Average Filter-Asymmetric Denoising Autoencoder.

Supervisory control and data acquisition (SCADA) systems are widely utilized in power equipment for condition monitoring. For the collected data, there generally exists a problem-missing data of different types and patterns. This leads to the poor quality and utilization difficulties of the collected data. To address this problem, this paper customizes methodology that combines an asymmetric denoising autoencoder (ADAE) and moving average filter (MAF) to perform accurate missing data imputation. First, convolution and gated recurrent unit (GRU) are applied to the encoder of the ADAE, while the decoder still utilizes the fully connected layers to form an asymmetric network structure. The ADAE extracts the local periodic and temporal features from monitoring data and then decodes the features to realize the imputation of the multi-type missing. On this basis, according to the continuity of power data in the time domain, the MAF is utilized to fuse the prior knowledge of the neighborhood of missing data to secondarily optimize the imputed data. Case studies reveal that the developed method achieves greater accuracy compared to existing models. This paper adopts experiments under different scenarios to justify that the MAF-ADAE method applies to actual power equipment monitoring data imputation.

Brain functional and effective connectivity based on electroencephalography recordings: A review.

Functional connectivity and effective connectivity of the human brain, representing statistical dependence and directed information flow between cortical regions, significantly contribute to the study of the intrinsic brain network and its functional mechanism. Many recent studies on electroencephalography (EEG) have been focusing on modeling and estimating brain connectivity due to increasing evidence that it can help better understand various brain neurological conditions. However, there is a lack of a comprehensive updated review on studies of EEG-based brain connectivity, particularly on visualization options and associated machine learning applications, aiming to translate those techniques into useful clinical tools. This article reviews EEG-based functional and effective connectivity studies undertaken over the last few years, in terms of estimation, visualization, and applications associated with machine learning classifiers. Methods are explored and discussed from various dimensions, such as either linear or nonlinear, parametric or nonparametric, time-based, and frequency-based or time-frequency-based. Then it is followed by a novel review of brain connectivity visualization methods, grouped by Heat Map, data statistics, and Head Map, aiming to explore the variation of connectivity across different brain regions. Finally, the current challenges of related research and a roadmap for future related research are presented.

P300/CBP inhibition sensitizes mantle cell lymphoma to PI3Kδ inhibitor idelalisib.

Mantle cell lymphoma (MCL) is a lymphoproliferative disorder lacking reliable therapies. PI3K pathway contributes to the pathogenesis of MCL, serving as a potential target. However, idelalisib, an FDA-approved drug targeting PI3Kδ, has shown intrinsic resistance in MCL treatment. Here we report that a p300/CBP inhibitor, A-485, could overcome resistance to idelalisib in MCL cells in vitro and in vivo. A-485 was discovered in a combinational drug screening from an epigenetic compound library containing 45 small molecule modulators. We found that A-485, the highly selective catalytic inhibitor of p300 and CBP, was the most potent compound that enhanced the sensitivity of MCL cell line Z-138 to idelalisib. Combination of A-485 and idelalisib remarkably decreased the viability of three MCL cell lines tested. Co-treatment with A-485 and idelalisib in Maver-1 and Z-138 MCL cell xenograft mice for 3 weeks dramatically suppressed the tumor growth by reversing the unsustained inhibition in PI3K downstream signaling. We further demonstrated that p300/CBP inhibition decreased histone acetylation at RTKs gene promoters and reduced transcriptional upregulation of RTKs, thereby inhibiting the downstream persistent activation of MAPK/ERK signaling, which also contributed to the pathogenesis of MCL. Therefore, additional inhibition of p300/CBP blocked MAPK/ERK signaling, which rendered maintaining activation to PI3K-mTOR downstream signals p-S6 and p-4E-BP1, thus leading to suppression of cell growth and tumor progression and eliminating the intrinsic resistance to idelalisib ultimately. Our results provide a promising combination therapy for MCL and highlight the potential use of epigenetic inhibitors targeting p300/CBP to reverse drug resistance in tumor.

Natural product 1,2,3,4,6-penta-O-galloyl-ß-D-glucopyranose is a reversible inhibitor of glyceraldehyde 3-phosphate dehydrogenase.

Aerobic glycolysis, also known as the Warburg effect, is a hallmark of cancer cell glucose metabolism and plays a crucial role in the activation of various types of immune cells. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) catalyzes the conversion of D-glyceraldehyde 3-phosphate to D-glycerate 1,3-bisphosphate in the 6th critical step in glycolysis. GAPDH exerts metabolic flux control during aerobic glycolysis and therefore is an attractive therapeutic target for cancer and autoimmune diseases. Recently, GAPDH inhibitors were reported to function through common suicide inactivation by covalent binding to the cysteine catalytic residue of GAPDH. Herein, by developing a high-throughput enzymatic screening assay, we discovered that the natural product 1,2,3,4,6-penta-O-galloyl-ß-D-glucopyranose (PGG) is an inhibitor of GAPDH with Ki = 0.5 µM. PGG blocks GAPDH activity by a reversible and NAD+ and Pi competitive mechanism, suggesting that it represents a novel class of GAPDH inhibitors. In-depth hydrogen deuterium exchange mass spectrometry (HDX-MS) analysis revealed that PGG binds to a region that disrupts NAD+ and inorganic phosphate binding, resulting in a distal conformational change at the GAPDH tetramer interface. In addition, structural modeling analysis indicated that PGG probably reversibly binds to the center pocket of GAPDH. Moreover, PGG inhibits LPS-stimulated macrophage activation by specific downregulation of GAPDH-dependent glucose consumption and lactate production. In summary, PGG represents a novel class of GAPDH inhibitors that probably reversibly binds to the center pocket of GAPDH. Our study sheds new light on factors for designing a more potent and specific inhibitor of GAPDH for future therapeutic applications.

A multi-targeting drug design strategy for identifying potent anti-SARS-CoV-2 inhibitors.

The COVID-19, caused by SARS-CoV-2, is threatening public health, and there is no effective treatment. In this study, we have implemented a multi-targeted anti-viral drug design strategy to discover highly potent SARS-CoV-2 inhibitors, which simultaneously act on the host ribosome, viral RNA as well as RNA-dependent RNA polymerases, and nucleocapsid protein of the virus, to impair viral translation, frameshifting, replication, and assembly. Driven by this strategy, three alkaloids, including lycorine, emetine, and cephaeline, were discovered to inhibit SARS-CoV-2 with EC50 values of low nanomolar levels potently. The findings in this work demonstrate the feasibility of this multi-targeting drug design strategy and provide a rationale for designing more potent anti-virus drugs.

Safety, tolerability, and pharmacokinetics of VV116, an oral nucleoside analog against SARS-CoV-2, in Chinese healthy subjects.

VV116 (JT001) is an oral drug candidate of nucleoside analog against SARS-CoV-2. The purpose of the three phase I studies was to evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending oral doses of VV116 in healthy subjects, as well as the effect of food on the pharmacokinetics and safety of VV116. Three studies were launched sequentially: Study 1 (single ascending-dose study, SAD), Study 2 (multiple ascending-dose study, MAD), and Study 3 (food-effect study, FE). A total of 86 healthy subjects were enrolled in the studies. VV116 tablets or placebo were administered per protocol requirements. Blood samples were collected at the scheduled time points for pharmacokinetic analysis. 116-N1, the metabolite of VV116, was detected in plasma and calculated for the PK parameters. In SAD, AUC and Cmax increased in an approximately dose-proportional manner in the dose range of 25-800 mg. T1/2 was within 4.80-6.95 h. In MAD, the accumulation ratio for Cmax and AUC indicated a slight accumulation upon repeated dosing of VV116. In FE, the standard meal had no effect on Cmax and AUC of VV116. No serious adverse event occurred in the studies, and no subject withdrew from the studies due to adverse events. Thus, VV116 exhibited satisfactory safety and tolerability in healthy subjects, which supports the continued investigation of VV116 in patients with COVID-19.

Discovery of potential small molecular SARS-CoV-2 entry blockers targeting the spike protein.

An epidemic of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. SARS-CoV-2 relies on its spike protein to invade host cells by interacting with the human receptor protein Angiotensin-Converting Enzymes 2 (ACE2). Therefore, designing an antibody or small-molecular entry blockers is of great significance for virus prevention and treatment. This study identified five potential small molecular anti-virus blockers via targeting SARS-CoV-2 spike protein by combining in silico technologies with in vitro experimental methods. The five molecules were natural products that binding to the RBD domain of SARS-CoV-2 was qualitatively and quantitively validated by both native Mass Spectrometry (MS) and Surface Plasmon Resonance (SPR). Anti-viral activity assays showed that the optimal molecule, H69C2, had a strong binding affinity (dissociation constant KD) of 0.0947 µM and anti-virus IC50 of 85.75 µM.