Feline infectious peritonitis (FIP) is a fatal illness caused by a mutated feline coronavirus (FCoV). This disease is characterized by its complexity, resulting from systemic infection, antibody-dependent enhancement (ADE), and challenges in accessing effective therapeutics. Extract derived from Vigna radiata (L.) R. Wilczek (VRE) exhibits various pharmacological effects, including antiviral activity. This study aimed to investigate the antiviral potential of VRE against FCoV, addressing the urgent need to advance the treatment of FIP. We explored the anti-FCoV activity, antiviral mechanism, and combinational application of VRE by means of in vitro antiviral assays. Our findings reveal that VRE effectively inhibited the cytopathic effect induced by FCoV, reduced viral proliferation, and downregulated spike protein expression. Moreover, VRE blocked FCoV in the early and late infection stages and was effective under in vitro ADE infection. Notably, when combined with VRE, the polymerase inhibitor GS-441524 or protease inhibitor GC376 suppressed FCoV more effectively than monotherapy. In conclusion, this study characterizes the antiviral property of VRE against FCoV in vitro, and VRE possesses therapeutic potential for FCoV treatment.

2024-12-01·SLAS Technology

High-resolution acoustic ejection mass spectrometry for high-throughput library screening

Article

作者: Michael, Sam ; Wilson, Kelli M. ; Janiszewski, John S ; Liu, Chang ; Hoxie, Nate ; Shen, Min ; Covey, Tom ; Gomba, Glenn ; Wilson, Kelli M ; Hall, Matthew D ; Verma, Meghav ; Shrimp, Jonathan H. ; Calabrese, David R. ; Janiszewski, John S. ; Itkin, Zina ; Calabrese, David R ; Hall, Matthew D. ; Burton, Lyle ; Shrimp, Jonathan H

An approach is described for high-throughput quality assessment of drug candidate libraries using high-resolution acoustic ejection mass spectrometry (AEMS). Sample introduction from 1536-well plates is demonstrated for this application using 2.5 nL acoustically dispensed sample droplets into an Open Port Interface (OPI) with pneumatically assisted electrospray ionization at a rate of one second per sample. Both positive and negative ionization are shown to be essential to extend the compound coverage of this protease inhibitor-focused library. Specialized software for efficiently interpreting this data in 1536-well format is presented. A new high-throughput method for quantifying the concentration of the components (HTQuant) is proposed that neither requires adding an internal standard to each well nor further encumbers the high-throughput workflow. This approach for quantitation requires highly reproducible peak areas, which is shown to be consistent within 4.4 % CV for a 1536-well plate analysis. An approach for troubleshooting the workflow based on the background ion current signal is also presented. The AEMS data is compared to the industry standard LC/PDA/ELSD/MS approach and shows similar coverage but at 180-fold greater throughput. Despite the same ionization process, both methods confirmed the presence of a small percentage of compounds in wells that the other did not. The data for this relatively small, focused library is compared to a larger, more chemically diverse library to indicate that this approach can be more generally applied beyond this single case study. This capability is particularly timely considering the growing implementation of artificial intelligence strategies that require the input of large amounts of high-quality data to formulate predictions relevant to the drug discovery process. The molecular structures of the 872-compound library analyzed here are included to begin the process of correlating molecular structures with ionization efficiency and other parameters as an initial step in this direction.

2024-12-01·Bioresource Technology

Lysozyme coupling protease pretreatment to relieve the humic acid inhibition on excess sludge anaerobic fermentation

Article

作者: Cai, Qiupeng ; Zhong, Yijie ; Duan, Shengye ; Zhang, Jie ; He, Junguo ; Pan, Xinlei ; Cui, Xinxin ; Zou, Xiang

The asynchronous dosed protease and lysozyme combination pretreatment was proved to be effective in enhancing the anaerobic fermentation of waste activated sludge (WAS). However, humic acid (HA) in the sludge could interact with hydrolase and restrain the hydrolysis efficiency, thus inhibiting short-chain fatty acids (SCFAs) production. This study investigated the effectiveness and mechanism of enzymatic pretreatment against HA. Results showed that the enzyme cocktail method increased the extracellular bioavailable contents by 34 %, which raised SCFAs production by 89.69 % (1269.65 mg COD /L). The balanced ratio of hydrolysis and fermentation communities suggested that the small molecular organics generated by the hydrolysis community could be sufficiently utilized by fermentation communities. The metabolism of amino acids and glucose was facilitated, and the activities of key enzymes were enhanced. These results clarified the effect of asynchronous enzyme cocktail pretreatment against HA inhibition and contributed to SCFAs production, which offered fresh perspectives on carbon recovery.

项与 Protease Inhibitor(Atea Pharmaceuticals) 相关的新闻（医药）

2024-09-26

·PipelineReview

Enanta Pharmaceuticals Announces Positive Topline Results for EDP-323 in a Phase 2a Human Challenge Study of Healthy Adults Infected With Respiratory Syncytial Virus (RSV)

WATERTOWN, MA, USA I September 26, 2024 I Enanta Pharmaceuticals, Inc. (NASDAQ:ENTA), a clinical-stage biotechnology company dedicated to creating best-in-class small molecule drugs for virology and immunology indications, today announced positive topline results from a Phase 2a human challenge study of EDP-323 in healthy adults infected with respiratory syncytial virus (RSV). These data demonstrated that EDP-323 was generally safe and well-tolerated and achieved an 85-87% reduction in viral load area under the curve (AUC) by qRT-PCR (p<0.0001), a 97-98% reduction in infectious viral load AUC by viral culture (p<0.0001), and a 66-78% reduction of total clinical symptoms score AUC (p<0.0001) compared to placebo. EDP-323, which received Fast Track designation from the U.S. Food and Drug Administration (FDA), is a novel L-protein inhibitor in development as a once-daily oral treatment for RSV. “We are excited about these impressive data that demonstrate a rapid and sustained reduction in viral load. These results are among the strongest ever reported in an RSV challenge study, raising the high bar set by zelicapavir. The significant antiviral activity and symptom alleviation observed in this study highlight EDP-323’s potential as a safe, highly effective, direct-acting antiviral for the treatment of RSV,” said Scott T. Rottinghaus, M.D., Chief Medical Officer of Enanta Pharmaceuticals. “These EDP-323 results represent a meaningful advancement toward achieving our longstanding goal of developing new medicines to treat respiratory infections such as RSV, as there remains a substantial need for safe and effective oral treatments. Enanta has the leading portfolio of potent RSV replication inhibitors, with EDP-323, our L-protein inhibitor, and zelicapavir, our N-protein inhibitor, both in Phase 2 development. These distinct mechanisms have the potential to be developed as once-daily single agents or in combination for specific patient populations,” added Jay R. Luly, Ph.D., President and Chief Executive Officer of Enanta Pharmaceuticals. EDP-323 Phase 2a Challenge Study Topline Results This Phase 2a study was a randomized, double-blind, placebo-controlled, human challenge study of 142 healthy adult participants inoculated with RSV. Randomized participants (n=141) received either a once-daily (QD) 600 mg dose of EDP-323 for five days [high dose, n=47], a single 600 mg loading dose on day one followed by a 200 mg once-daily (QD) dose of EDP-323 for four days [low dose, n=47], or placebo for five days [n=47]. The intent-to-treat-infected population (ITT-I) was defined as all randomized participants receiving challenge virus and at least one dose of study drug with confirmed RSV infection. EDP-323 demonstrated a rapid and sustained antiviral effect. A highly statistically significant reduction (p<0.0001) was observed for the primary efficacy endpoint of AUC for viral load as measured by qRT-PCR in the ITT-I population for each of the EDP-323 dosing groups as compared with placebo. Specifically, EDP-323 lowered viral load AUC by 85% in the high dose arm and 87% in the low dose arm compared to placebo. There was no statistically significant difference between the two EDP-323 dosing groups. A highly statistically significant reduction (p<0.0001) was observed for the secondary efficacy endpoint of AUC for infectious viral load as measured by quantitative culture in the ITT-I population for each of the EDP-323 dosing groups, with a reduction in viral culture AUC by 98% in the high dose arm and 97% in the low dose arm compared to placebo. There was no statistically significant difference between the two EDP-323 dosing groups. For the secondary efficacy endpoint of AUC for total symptom score, a highly statistically significant reduction (p<0.0001) was observed in the ITT-I population for each of the EDP-323 dosing groups, with a symptom reduction of 66% in the high dose arm and 78% in the low dose arm compared to placebo. There was no statistically significant difference between the two EDP-323 dosing groups. EDP-323 demonstrated favorable pharmacokinetics, supportive of once-daily dosing. Mean trough plasma concentrations were maintained at 16-fold above the protein-adjusted EC 90 with the low dose, and 35-fold above the protein-adjusted EC 90 with the high dose, for both RSV A and B strains. Overall, EDP-323 demonstrated a favorable safety profile over a 5-day dosing period and through 28 days of follow-up. Adverse events were similar between EDP-323 dosing groups and placebo. There were no serious adverse events, no severe adverse events, and no adverse events leading to treatment discontinuation or study withdrawal. Full data from the study will be presented at a future medical conference or in a peer-reviewed publication. Conference Call and Webcast Information Enanta will host a conference call and webcast today at 8:30 a.m. ET. The live webcast can be accessed at “ Events & Presentations ” in the investors section of Enanta’s website. To participate by phone, please register for the call here . It is recommended that participants register a minimum of 15 minutes before the call. Once registered, participants will receive an email with the dial-in information. The archived webcast will be available on Enanta’s website for approximately 30 days following the event. About EDP-323 EDP-323, a novel, oral, direct-acting antiviral selectively targeting the RSV L-protein, has received Fast Track designation by the U.S. Food and Drug Administration. In a Phase 1 study, EDP-323 was found to be generally safe and well-tolerated in healthy subjects up to 800 mg for up to seven days, with a pharmacokinetic profile supporting once-daily dosing and all doses achieving target exposures. In addition to its Phase 1 profile, EDP-323 is also supported by in vitro data demonstrating a significant reduction in RSV replication with picomolar potency in primary human bronchial epithelial cells infected with RSV A and B, and across a range of RSV clinical isolates and various cell types. In a mouse model of RSV infection, EDP-323 treatment was associated with dose-dependent decreases in viral load in the lung, reductions in lung immunopathology and decreases in pro-inflammatory cytokines, including IFNγ, TNFα, and IL1β. About Respiratory Syncytial Virus RSV is the most common cause of bronchiolitis (inflammation of the small airways in the lung) and pneumonia in children under one year of age in the United States and a significant cause of respiratory illness in older adults and immunocompromised individuals. 1 According to the Centers for Disease Control and Prevention, virtually all children in the United States get an RSV infection by the time they are two years old and one to two out of every 100 children younger than six months of age with an RSV infection may need to be hospitalized. 2 Globally, there are an estimated 33 million cases of RSV annually in children less than five years of age, with about 3 million hospitalized and up to approximately 120,000 dying each year from complications associated with the infection. 3 RSV represents a significant health threat for adults older than 65 years of age, with an estimated 177,000 hospitalizations and 14,000 deaths associated with RSV infections annually in the United States. 4 About Enanta Pharmaceuticals, Inc. Enanta is using its robust, chemistry-driven approach and drug discovery capabilities to become a leader in the discovery and development of small molecule drugs with an emphasis on indications in virology and immunology. Enanta’s research and development programs are currently focused on respiratory syncytial virus (RSV) and chronic spontaneous urticaria (CSU) and the company has previously advanced clinical-stage compounds for SARS-CoV-2 (COVID-19) and chronic hepatitis B virus (HBV) infection. Glecaprevir, a protease inhibitor discovered by Enanta, is part of one of the leading treatment regimens for curing chronic hepatitis c virus (HCV) infection and is sold by AbbVie in numerous countries under the tradenames MAVYRET ® (U.S.) and MAVIRET ® (ex-U.S.) (glecaprevir/pibrentasvir). A portion of Enanta’s royalties from HCV products developed under its collaboration with AbbVie contribute ongoing funding to Enanta’s operations. Please visit www.enanta.com for more information. SOURCE: Enanta Pharmaceuticals

临床结果临床1期快速通道临床2期

2024-09-06

·PRNewswire

Cytonics Announces Completion Of Enrollment For Phase 1 Clinical Study Evaluating CYT-108, A Novel Recombinant Protease Inhibitor, In Patients Suffering From Osteoarthritis Of The Knee

Top-line results from Phase 1 study expected in second quarter of 2025 JUPITER, Fla., Sept. 6, 2024 /PRNewswire/ -- Cytonics Corporation, a private biotechnology company developing biologic therapies for inflammatory musculoskeletal conditions, today announced completion of enrollment for their Phase 1 clinical study of CYT-108, a recombinant variant of the alpha-2-macroglobulin blood serum protease inhibitor, as a putative disease-modifying therapy for osteoarthritis (OA). This first-in-human clinical trial is a multi-center, 6-month, double-blind RCT (n=22, randomized 1:1 between treatment and placebo groups) evaluating the safety and efficacy of CYT-108 in patients with unilateral, mild-to-moderate, primary OA of the knee. The primary safety endpoints will measure CYT-108's tolerability when delivered via intra-articular injection directly into afflicted joints. The secondary efficacy endpoints will assess improvement in self-reported pain and mobility in the treated joint, and an exploratory endpoint will quantify peptide fragments found in blood serum as a biomarker for cartilage degradation. To date, no drug-related adverse events have been reported and CYT-108 appears well-tolerated in all patients. "We are thrilled to have completed enrollment of all 22 patients across our three clinical sites in Australia, beating our recruitment forecast by more than a month. This will expedite the Phase 1 clinical study report and our IND filing with the FDA in 2025, bringing us one step closer to developing the first and only disease-modifying therapy for osteoarthritis. We are thoroughly impressed by the recruitment efficiency of our clinical sites and look forward to continuing working with these researchers and clinicians as we advance into Phase 2." ~ Joey Bose, President & CEO, Cytonics Corp. About CYT-108 CYT-108 is a recombinant variant of the endogenous alpha-2-macroglobulin (A2M) blood serum protein. The "bait" region of the protein, which serves as a substrate for proteases, was engineered to increase its affinity for specific proteases that are known to play a significant role in the molecular pathogenesis of osteoarthritis. The combination of both highly specific and broad-spectrum protease inhibition activity of CYT-108 differentiates this novel biologic from other attempts to develop small molecule inhibitors that target a single proteases, positioning CYT-108 as an ideal disease-modifying candidate for osteoarthritis. The development of CYT-108 is predicated on the success of Cytonics' first-generation therapy, the Autologous Protease Inhibitor Concentrate (APIC) system, which is a 510(k) medical device that selectively enriches autologous A2M for intra-articular injection into joints containing articular cartilage (knee, shoulder, spine, hip, etc.). The clinical and commercial success of APIC uniquely de-risks the development of CYT-108 because it is already understood that high concentrations of A2M can be introduced into arthritic joints without significant side effects, and the treatment has achieved clinical and commercial success since it was first cleared by the FDA as a 510(k) device and sold in 2015. About Cytonics Corp. Cytonics, founded in 2006, is a private research and development company focused on developing molecular diagnostics and therapeutics for chronic musculoskeletal diseases such as osteoarthritis. The company's flagship product was a diagnostic test (the Fibronectin-Aggrecan Complex Test, FACT) which helps identify the source of joint pain and assists physicians in determining the most appropriate course of treatment. Cytonics then developed the Autologous Platelet-Integrated Concentrate (APIC) system which concentrates a therapeutic blood protein, A2M, from patients' own blood and injects the A2M-rich concentrate into damaged joints. APIC has been used to treat over 8,000 patients nationwide, saving thousands of patients from invasive joint replacement surgeries. The company has raised over $25M in private funding and was awarded $1.8M in grants from the NIH to pursue their innovative research. The company is currently pursuing Phase 1 clinical studies for their lead drug candidate, CYT-108, a recombinant variant of the endogenous alpha-2-macroglobuling protease inhibitor. If approved, CYT-108 may be the first and only disease-modifying therapy for osteoarthritis. Forward Looking Statements This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the progress of and plans related to the Company's product candidates, clinical studies and preclinical research and development programs, the therapeutic and market potential of the Company's research and development programs and product candidates, the Company's clinical and product development strategy, and the Company's expectations regarding progress and timelines. These and any other forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that the Company's research and development programs and product candidates may not demonstrate the requisite safety, efficacy, or other attributes to warrant further development or to achieve regulatory approval, the risk that results observed in prior studies of the Company's product candidates, including preclinical studies and clinical trials, will not be observed in ongoing or future studies involving these product candidates, the risk of a delay or difficulties in the manufacturing of the Company's product candidates or in the initiation and conduct of, or enrollment of patients in, any clinical trials, the risk that the Company may cease or delay preclinical or clinical development of any of its product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials, changes in the therapeutic, regulatory, or competitive landscape for which the Company's product candidates are being developed, the amount and type of data to be generated or otherwise to support regulatory approval, difficulties or delays in patient enrollment and continuation in the Company's ongoing and planned clinical trials, difficulties in manufacturing or supplying the Company's product candidates for clinical testing, and any adverse events or other negative results that may be observed during preclinical or clinical development), the risk that its product candidates may not produce therapeutic benefits or may cause other unanticipated adverse effects, and the risk that the Company may incur operating expenses in amounts greater than anticipated. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Company's actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Company's periodic filings with the Securities and Exchange Commission (), including but not limited to the Company's most recently filed periodic report, and from time to time in the Company's press releases and other investor communications. Cytonics Corporation is providing the information in this release as of this date and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise. SOURCE Cytonics Corporation

临床1期

2024-08-19

·GlobeNewswire-Health Care

Cocrystal Pharma to Highlight Near-term Clinical Milestones During Presentations at Two Upcoming Investment Conferences

BOTHELL, Wash., Aug. 19, 2024 (GLOBE NEWSWIRE) -- Cocrystal Pharma, Inc.’s (Nasdaq: COCP) management announces its participation in the upcoming Virtual Investor Summit Microcap Forum in August and the H.C. Wainwright 26th Annual Global Investment Conference in September. “We look forward to showcasing key near-term clinical milestones at two upcoming investment conferences,” said James Martin, CFO and co-CEO of Cocrystal. “We expect to report topline results in 2024 from our influenza A Phase 2a challenge study with our novel oral PB2 inhibitor CC-42344 with the final report expected to be filed in 2025. We also expect to report topline results from the Phase 1 multiple-ascending cohorts in late 2024 or early 2025 with our novel oral protease inhibitor CDI-988 for the treatment of norovirus and coronavirus infections.” Virtual Investor Summit Microcap Forum The presentation and Q&A session will begin Tuesday, August 20, 2024 at 9:00 a.m. Eastern timeInvestors can register here to view the live presentation and to ask questions H.C. Wainwright 26th Annual Global Investment Conference An on-demand presentation will be available to conference participants on the H.C. Wainwright platform beginning Monday, September 9, 2024 at 7:00 a.m. Eastern timeManagement will be available for in-person and virtual one-on-one meeting throughout the conference; institutional investors and industry professionals can register to attend the conference virtually or in-person at the Lotte New York PalaceThe presentation will be available on the Company’s website CC-42344 – Pandemic and Seasonal Influenza A PB2 Inhibitor CC-42344 is our novel, broad-spectrum antiviral candidate to treat pandemic and seasonal influenza A. CC-42344 inhibits influenza A’s viral replication by binding to a highly conserved PB2 site. We discovered CC-42344 using our proprietary structure-based drug discovery platform. We are conducting a Phase 2a influenza challenge study in the United Kingdom to evaluate safety and efficacy in healthy volunteers. CC-42344 demonstrated favorable safety and tolerability, and pharmacokinetics profiles in a Phase 1 study. In vitro testing indicated CC-42344’s potent antiviral activity against influenza A strains as well as against pandemic and seasonal strains and strains resistant to Tamiflu® and Xofluza®. CDI-988 – Pan-viral Protease Inhibitor Against Noroviruses and CoronavirusesWe have developed a novel protease inhibitor, CDI-988, to treat norovirus and coronavirus infection, including SARS-CoV-2 and its variants. CDI-988 was specifically designed and developed as an oral broad-spectrum antiviral inhibitor using our structure-based drug discovery platform to bind to a highly conserved region of noroviruses, coronaviruses and other 3CL viral proteases. CDI-988 is being evaluated in a randomized, double-blind, placebo-controlled Phase 1 trial for safety, tolerability and pharmacokinetics. About Cocrystal Pharma, Inc.Cocrystal Pharma, Inc. is a clinical-stage biotechnology company discovering and developing novel antiviral therapeutics that target the replication process of influenza viruses, coronaviruses (including SARS-CoV-2), noroviruses and hepatitis C viruses. Cocrystal employs unique structure-based technologies and Nobel Prize-winning expertise to create first- and best-in-class antiviral drugs. For further information about Cocrystal, please visit www.cocrystalpharma.com. Cautionary Note Regarding Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the potential characteristics and efficacy of product candidates and the expected timing and results of the clinical trials for such product candidates. The words "believe," "may," "estimate," "continue," "anticipate," "intend," "should," "plan," "could," "target," "potential," "is likely," "will," "expect" and similar expressions, as they relate to us, are intended to identify forward-looking statements. We have based these forward-looking statements largely on our current expectations and projections about future events. Some or all of the events anticipated by these forward-looking statements may not occur. Important factors that could cause actual results to differ from those in the forward-looking statements include, but are not limited to, risks relating to our ability to proceed with and complete clinical trials including recruiting volunteers and procuring materials for such studies by our clinical research organizations and vendors, the results of such studies, our and our collaboration partners’ technology and software performing as expected, general risks arising from clinical studies, receipt of regulatory approvals, regulatory changes, and potential development of effective treatments and/or vaccines by competitors, including as part of the programs financed by the U.S. and foreign governments, potential mutations in a virus we are targeting that may result in variants that are resistant to a product candidate we develop. Further information on our risk factors is contained in our filings with the SEC, including our Annual Report on Form 10-K for the year ended December 31, 2023. Any forward-looking statement made by us herein speaks only as of the date on which it is made. Factors or events that could cause our actual results to differ may emerge from time to time, and it is not possible for us to predict all of them. We undertake no obligation to publicly update any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by law. Investor Contact:LHA Investor RelationsJody Cain310-691-7100jcain@lhai.com Media Contact:JQA PartnersJules Abraham917-885-7378Jabraham@jqapartners.com # # #

临床1期临床结果临床2期

100 项与 Protease Inhibitor(Atea Pharmaceuticals) 相关的药物交易

登录后查看更多信息