Biology subjects

Sen, C.

Publications and source records attributed to Sen, C..

15 recordsLinked to original sources

bioRxiv2026

HighFold-Lasso: Topology-Guided Prediction of Lasso Peptide Structures Using AlphaFold3

Lasso peptides are a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) characterized by a mechanically interlocked topology, in which the C-terminal tail is threaded through an N-terminal macrolactam ring formed by an isopeptide bond. This unique topology often confers high thermal stability and resistance to proteolytic degradation. However, the isopeptide linkage, threaded topology, and class-specific disulfide connectivity make lasso peptide structures difficult to reconstruct reliably using general-purpose structure prediction models. Here, we developed HighFold-Lasso, which combines custom covalent connectivity with lasso scaffold-guided adaptive low-noise initialization to enable conditional structure generation guided by lasso conformational priors. On a test set of 52 experimentally determined structures, HighFold-Lasso achieved a 100% lasso topology success rate, with a mean RMSD C-alpha of 1.942 Angstrom for the ring-loop region and 2.375 Angstrom for the full peptide. The framework supports modeling of the four classical lasso peptide classes (I-IV) and can represent noncanonical amino acids, providing computational support for structure-function studies and molecular engineering of lasso peptides.

bioinformatics↗

bioRxiv2026

Transcriptional and spatial profiling of fibroblasts from human lungs highlights CTHRC1+ cells as fibrogenic signaling hubs in fibrosis

Lung fibroblasts are key regulators of tissue homeostasis and extracellular matrix (ECM) remodeling, and their aberrant activation drives the progressive parenchymal scarring characteristic of idiopathic pulmonary fibrosis (IPF), a fatal disease with limited therapeutic options. Despite their central pathogenic role, lung fibroblasts are difficult to isolate due to their embedded position within the ECM, and standard in vitro culture conditions may lead to the loss of their native functional and transcriptional characteristics, hampering the study of fibroblast behavior in disease. The transcriptional heterogeneity of lung fibroblast subtypes and the extent to which culture-induced alterations diverge from native tissue signatures remain poorly understood. Here, we integrated single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics of lung tissue from IPF patients and age-matched healthy donors with transcriptomic profiling of cultured fibroblasts collected at passages 1 and 6 after isolation using three optimized protocols: whole lung cell suspension (WLCS), negative fraction enrichment, and outgrowth. Tissue-based analysis identified six transcriptionally distinct mesenchymal subtypes: alveolar, adventitial, inflammatory, peribronchial, CTHRC1+ and smooth muscle cell (SMC). The fibroblast subtype CTHRC1+ represented the most transcriptionally activated pro-fibrotic subtype, showing the greatest upregulation of ECM biosynthesis genes, a prominent role in intercellular communication, and preferential enrichment within fibroblastic foci in IPF lung tissue. Pseudotime trajectory analysis supported a directional transcriptional continuum from alveolar and inflammatory fibroblasts toward the CTHRC1+ state, driven by coordinated activation of pro-fibrotic transcription factors, including RUNX2, CREB3L1, and SCX. In vitro culture progressively reshaped fibroblast transcriptional identity relative to native tissue, with increased collagen and matrix metalloproteinase (MMP) expression during passaging, loss of distinct CTHRC1+ fibroblasts, and gain of alveolar fibroblasts displaying pro-fibrotic activation across all isolation protocols. These findings provide a high-resolution transcriptional map of lung fibroblast heterogeneity in IPF and highlight critical limitations of standard in vitro culture systems for recapitulating native fibroblast diversity, with important implications for the development and evaluation of fibroblast-targeted therapeutic strategies in IPF.

molecular biology↗

bioRxiv2026

Modeling cell-cell interactions to advance drug discovery in Idiopathic Pulmonary Fibrosis

BackgroundIdiopathic Pulmonary Fibrosis (IPF) is characterized by scarring and remodeling of lung tissue, leading to progressive pulmonary dysfunction. Currently, very little is known about the steps involved in disease initiation and progression because models of IPF poorly replicate these processes. However, understanding the pathogenesis of IPF is essential for developing effective therapies. To address this, we have developed a scaffold-based co-culture IPF organoid that uses healthy and diseased human primary and iPSC-derived alveolar epithelial cells and fibroblasts to recapitulate the cellular communication and cell fate during progressive fibrosis. MethodsWe generated microbead scaffolds that mimic alveolar air-sacs and coated them in a rotating bioreactor with primary lung fibroblasts and induced pluripotent stem cell-derived type 2 alveolar cells (iAT2s). iAT2s with the surfactant protein C (SFTPC) I73T variant and the syngeneic corrected control iAT2s were cultured with primary healthy and IPF fibroblasts in different combinations. The epithelial-mesenchymal interactions during fibrosis initiation and progression were evaluated by single-cell RNA sequencing. ResultsWe found that the interaction between epithelial cells and fibroblasts plays a key role in inducing fibrotic responses in this model, with the secretion of chemokines, cytokines, TGF{beta}, and matrix metalloproteinases that mirror those observed in the serum of patients with pulmonary fibrosis. Single-cell RNA sequencing revealed the emergence of many cell subtypes observed in progressive lung fibrosis, along with key cellular interactions that correlated with the initial upregulation of fibrosis pathways, extracellular matrix (ECM) remodeling, inflammation, and changes in lipid metabolism. The anti-fibrotic compounds, Nintedanib and the TGF{beta} inhibitor, SB431542, demonstrated dose-dependent efficacy in the model, with IC50 values comparable to those observed in the clinic, and significantly reduced secretion of fibrosis-related factors. ConclusionOverall, this study shows that the three-dimensional, reductionist, cell co-culture organoid effectively models several components of progressive lung fibrosis, facilitating the investigation of epithelial-mesenchymal interactions and serving as a patient-relevant model to better predict the efficacy of therapeutics in the clinic.

cell biology↗

bioRxiv2026

Bidirectional fibrogenic cross-talk revealed in a human iPSC-derived epithelial-mesenchymal co-culture model of pulmonary fibrosis

Pulmonary fibrosis (PF) can arise from mutations in alveolar epithelial type 2 (AT2) cell-specific genes, but manifests in fibrotic activation of mesenchymal cells, thus involving fibrogenic epithelial-mesenchymal crosstalk. The ligand-receptor interactions underlying the onset and early progression of PF remain poorly understood. Induced pluripotent stem cell (iPSC)-derived models are powerful tools to study respiratory diseases, yet are currently limited to reductionist single lineage epithelial models or multi-lineage systems that lack purity and lung-specificity of the mesenchyme. Here we generate a human iPSC line carrying both a lung mesenchyme-specific reporter (TBX4-LERtdTomato) and a reporter for mesenchymal activation/differentiation (ACTA2GFP). Applying this line, we develop a directed differentiation protocol capable of generating cells that express key molecular and functional features of primary human developing lung mesenchyme across multiple iPSC genetic backgrounds. We then establish co-cultures of these iPSC-derived lung mesenchymal cells (iLM) with patient-specific iPSC-derived alveolar epithelial type 2 cells (iAT2s) carrying an SFTPCI73T mutation as a model for PF. We find increased expression of fibrotic markers in co-cultures with mutant iAT2s as compared to co-cultures with gene-corrected iAT2s. Moreover, mutant iAT2s express markers of alveolar-basal intermediate (ABI) cells only in the presence of iLM, suggesting that bidirectional crosstalk promotes this aberrant cell state. We identify ligand-receptor pairs enriched in co-cultures with mutant iAT2s, including TGF{beta}, multiple integrins, and additional genes that have not been previously linked to PF. Finally, we show that small molecule-mediated inhibition of TGF{beta} or integrins V{beta}1/V{beta}6 attenuates both fibrotic mesenchymal activation and the presence of ABI cells in iLM/iAT2 co-cultures. Thus, we have established a human iPSC-derived co-culture system that recapitulates key molecular hallmarks of bidirectional fibrogenic epithelial-mesenchymal crosstalk in pulmonary fibrosis, and enables the identification and study of potentially druggable pathways involved in disease initiation and progression.

molecular biology↗

bioRxiv2025

PPIKB: A Comprehensive Knowledge Base and Analysis Platform for Protein Peptide Interactions Based on Literature and Patents

Protein-protein interactions (PPIs) underpin a multitude of fundamental biological processes and represent critical therapeutic targets. Peptide compounds--owing to their structural flexibility, high target specificity, and the combined advantages of small molecules and biologics--have emerged as powerful modulators of these interactions. However, the exponential growth of scientific publications and patent filings poses a significant challenge for the systematic integration of protein-peptide interaction (PPepI) data. To address this, we implemented a high-throughput extraction pipeline powered by large language models (LLMs) to harvest affinity data from both research articles and patents, followed by rigorous manual curation. Applying this approach to 4,241 research papers and 483 patents published between 1972 and 2025, we compiled 21,760 manually validated quantitative affinity entries encompassing 2,013 unique protein targets derived from human, mouse, rat, viral, bacterial, and other species. In parallel, we consolidated 18,005 structural entries of protein-peptide complexes from the Protein Data Bank and associated literature. Leveraging these comprehensive datasets, we developed PPIKB, a user-friendly database and analysis platform that enables efficient querying, visualization, and in-depth analysis of protein-peptide interactions. PPIKB also provides a suite of tools tailored to facilitate peptide-based drug discovery, protein engineering, and systems-level biological research. By combining state-of-the-art text-mining technologies with expert validation, PPIKB sets a new standard for accessibility and utility in the field of protein-peptide interaction data resources. Access PPIKB at: https://ppikb.duanlab.ac

bioinformatics↗

bioRxiv2025

Accurate structure prediction of cyclic peptides containing unnatural amino acids using HighFold3

In recent years, cyclic peptides have emerged as a research hotspot in drug development due to their excellent stability, high specificity, and potential to penetrate intracellular targets. However, existing computational models still face challenges in making accurate predictions of the structures of cyclic peptides containing unnatural amino acids (unAAs), thereby limiting their application in drug design. The release of AlphaFold 3 (AF3) has significantly improved the modeling capability of biomolecular complexes and supports the definition of unAAs through residue modifications using the CCD database (Chemical Component Dictionary). Yet, its reliance on structures already present in the training library limits its ability to accurately predict cyclic peptide structures. Base on the AlphaFold 3 framework, we developed HighFold3, which comprises two sub-models: HighFold3-Linear and HighFold3-Cyclic, designed for predicting the structures of linear and cyclic peptides, respectively. Our research results show that, by incorporating a cyclic peptide positional preference matrix, HighFold3 achieves superior performance over other models (HighFold, HighFold2, and CyclicBoltz1) in predicting cyclic peptide structures, particularly excelling in complex cyclic peptides containing unAAs. HighFold3 provides an efficient tool for cyclic peptide drug design, promising to advance the application of cyclic peptides in targeted therapy, antibacterial treatments, and cellular penetration.

bioinformatics↗

bioRxiv2024

Scalable Hypothalamic Arcuate Neuron Differentiation from Human Pluripotent Stem Cells Suitable for Modeling Metabolic and Reproductive Disorders

The hypothalamus, composed of several nuclei, is essential for maintaining our bodys homeostasis. The arcuate nucleus (ARC), located in the mediobasal hypothalamus, contains neuronal populations with eminent roles in energy and glucose homeostasis as well as reproduction. These neuronal populations are of great interest for translational research. To fulfill this promise, we used a robotic cell culture platform to provide a scalable and chemically defined approach for differentiating human pluripotent stem cells (hPSCs) into pro-opiomelanocortin (POMC), somatostatin (SST), tyrosine hydroxylase (TH) and gonadotropin-releasing hormone (GnRH) neuronal subpopulations with an ARC-like signature. This robust approach is reproducible across several distinct hPSC lines and exhibits a stepwise induction of key ventral diencephalon and ARC markers in transcriptomic profiling experiments. This is further corroborated by direct comparison to human fetal hypothalamus, and the enriched expression of genes implicated in obesity and type 2 diabetes (T2D). Genome-wide chromatin accessibility profiling by ATAC-seq identified accessible regulatory regions that can be utilized to predict candidate enhancers related to metabolic disorders and hypothalamic development. In depth molecular, cellular, and functional experiments unveiled the responsiveness of the hPSC-derived hypothalamic neurons to hormonal stimuli, such as insulin, neuropeptides including kisspeptin, and incretin mimetic drugs such as Exendin-4, highlighting their potential utility as physiologically relevant cellular models for disease studies. In addition, differential glucose and insulin treatments uncovered adaptability within the generated ARC neurons in the dynamic regulation of POMC and insulin receptors. In summary, the establishment of this model represents a novel, chemically defined, and scalable platform for manufacturing large numbers of hypothalamic arcuate neurons and serves as a valuable resource for modeling metabolic and reproductive disorders.

developmental biology↗

bioRxiv2024

Loss of cell junctional components and matrix alterations drive cell desquamation and fibrotic changes in Idiopathic Pulmonary Fibrosis

The distal bronchioles in Idiopathic Pulmonary Fibrosis (IPF) exhibit histopathological abnormalities such as bronchiolization, peribronchiolar fibrosis and honeycomb cysts that contribute to the overall architectural remodeling of lung tissue seen in the disease. Here we describe an additional histopathologic finding of epithelial desquamation in patients with IPF, wherein epithelial cells detach from the basement membrane of the distal bronchioles. To understand the mechanism driving this pathology, we performed spatial transcriptomics of the epithelial cells and spatial proteomics of the basement membrane of the distal bronchioles from IPF patients and patients with no prior history of lung disease. Our findings reveal a downregulation of cell junctional components, upregulation of epithelial-mesenchymal transition signatures and dysregulated basement membrane matrix in IPF distal bronchioles, facilitating epithelial desquamation. Further, functional assays identified regulation between Collagen IV in the matrix, and the junctional genes JUP and PLEC, that is crucial for maintaining distal bronchiolar homeostasis. In IPF, this balanced regulation between matrix and cell-junctions is disrupted, leading to loss of epithelial adhesion, peribronchiolar fibrosis and epithelial desquamation. Overall, our study suggests that in IPF the interplay between the loss of cell junctions and a dysregulated matrix results in desquamation of distal bronchiolar epithelium and lung remodeling, exacerbating the disease. One Sentence SummaryTwo-way regulation of cell junctional proteins and matrix proteins drives cellular desquamation and fibrosis in the distal bronchioles of patients with Idiopathic Pulmonary Fibrosis.

pathology↗

bioRxiv2024

High Throughput Screening with a Primary Human Mucociliary Airway Model Identifies a Small Molecule with Anti-SARS-CoV-2 Activity

Respiratory viruses (e.g. influenza, RSV, SARS etc.) attack the proximal airway and cause a wide spectrum of diseases for which we have limited therapies. To date, a few primary human stem cell-based models of the proximal airway have been reported for drug discovery but scaling them up to a higher throughput platform remains a significant challenge. Here we present a microscale, primary human stem cell-based proximal airway model of SARS-CoV-2 infection, which is amenable to moderate-to-high throughput drug screening. The model recapitulates the heterogeneity of infection seen among different patients and with different SARS-CoV-2 variants. We applied this model to screen 2100 compounds from targeted drug libraries using an image-based quantification method. While there were heterogeneous responses across variants for host factor targeting compounds, the direct acting antivirals showed a consistent response and we characterized a new antiviral drug that is effective against both the parental strain and the Omicron variant.

cell biology↗

bioRxiv2023

Small cell lung cancer co-culture organoids provide insights into cancer cell survival after chemotherapy

Small-cell-lung-cancer (SCLC) has the worst prognosis of all lung cancers because of a high incidence of relapse after therapy. We developed a bioengineered 3-dimensional (3D) SCLC co-culture organoid as a phenotypic tool to study SCLC tumor kinetics and SCLC-fibroblast interactions during relapse. We used functionalized alginate microbeads as a scaffold to mimic lung alveolar architecture and co-cultured SCLC cell lines with primary adult lung fibroblasts (ALF). We found that SCLCs in the model proliferated extensively, invaded the microbead scaffold and formed tumors within just 7 days. We compared the bioengineered tumors with patient tumors and found them to recapitulate the pathology and immunophenotyping of the patient tumors better than the PDX model developed from the same SCLC cell line. When treated with standard chemotherapy drugs, etoposide and cisplatin, the organoid recapitulated relapse after chemotherapy. Co-culture of the SCLC cells with ALFs revealed that the fibroblasts play a key role in inducing faster and more robust SCLC cell regrowth in the model. This was a paracrine effect as conditioned medium from the same fibroblasts was responsible for this accelerated cell regrowth. This model is also amenable to high throughput phenotypic or targeted drug screening to find new therapeutics for SCLC.

bioengineering↗

bioRxiv2022

Hippo Signaling Pathway Activation during SARS-CoV-2 Infection Contributes to Host Antiviral Response

SARS-CoV-2, responsible for the COVID-19 pandemic, causes respiratory failure and damage to multiple organ systems. The emergence of viral variants poses a risk of vaccine failures and prolongation of the pandemic. However, our understanding of the molecular basis of SARS-CoV-2 infection and subsequent COVID-19 pathophysiology is limited. In this study, we have uncovered a critical role for the evolutionarily conserved Hippo signaling pathway in COVID-19 pathogenesis. Given the complexity of COVID-19 associated cell injury and immunopathogenesis processes, we investigated Hippo pathway dynamics in SARS-CoV-2 infection by utilizing COVID-19 lung samples, and human cell models based on pluripotent stem cell-derived cardiomyocytes (PSC-CMs) and human primary lung air-liquid interface (ALI) cultures. SARS-CoV-2 infection caused activation of the Hippo signaling pathway in COVID-19 lung and in vitro cultures. Both parental and Delta variant of concern (VOC) strains induced Hippo pathway. The chemical inhibition and gene knockdown of upstream kinases MST1/2 and LATS1 resulted in significantly enhanced SARS-CoV-2 replication, indicating antiviral roles. Verteporfin a pharmacological inhibitor of the Hippo pathway downstream transactivator, YAP, significantly reduced virus replication. These results delineate a direct antiviral role for Hippo signaling in SARS-CoV-2 infection and the potential for this pathway to be pharmacologically targeted to treat COVID-19.

microbiology↗

bioRxiv2020

Suppression of miR-155 attenuates lung cytokine storm induced by SARS-CoV-2 infection in human ACE2-transgenic mice

Coronavirus disease 2019 (COVID-19) is a recent global pandemic. It is a deadly human viral disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with a high rate of infection, morbidity and mortality. Therefore, there is a great urgency to develop new therapies to control, treat and prevent this disease. Endogenous microRNAs (miRNAs, miRs) of the viral host are key molecules in preventing viral entry and replication, and building an antiviral cellular defense. Here, we have analyzed the role of miR-155, one of the most powerful drivers of host antiviral responses including immune and inflammatory responses, in the pathogenicity of SARS-CoV-2 infection. Subsequently, we have analyzed the potency of anti-miR-155 therapy in a COVID-19 mouse model (mice transgenic for human angiotensin I-converting enzyme 2 receptor (tg-mice hACE2)). We report for the first time that miR-155 expression is elevated in COVID-19 patients. Further, our data indicate that the viral load as well as miR-155 levels are higher in male relative to female patients. Moreover, we find that the delivery of anti-miR-155 to SARS-CoV-2-infected tg-mice hACE2 effectively suppresses miR-155 expression, and leads to improved survival and clinical scores. Importantly, anti-miR-155-treated tg-mice hACE2 infected with SARS-CoV-2 not only exhibit reduced levels of pro-inflammatory cytokines, but also have increased anti-viral and anti-inflammatory cytokine responses in the lungs. Thus, our study suggests anti-miR-155 as a novel therapy for mitigating the lung cytokine storm induced by SARS-CoV-2 infection.

immunology↗

bioRxiv2020

Direct exposure to SARS-CoV-2 and cigarette smoke increases infection severity and alters the stemcell-derived airway repair response

Most demographic studies are now associating current smoking status with increased risk of severe COVID-19 and mortality from the disease but there remain many questions about how direct cigarette smoke exposure affects SARS-CoV-2 airway cell infection. We directly exposed mucociliary air-liquid interface (ALI) cultures derived from primary human nonsmoker airway basal stem cells (ABSCs) to short term cigarette smoke and infected them with live SARS-CoV-2. We found an increase in the number of infected airway cells after cigarette smoke exposure as well as an increased number of apoptotic cells. Cigarette smoke exposure alone caused airway injury that resulted in an increased number of ABSCs, which proliferate to repair the airway. But we found that acute SARS-CoV-2 infection or the combination of exposure to cigarette smoke and SARS-CoV-2 did not induce ABSC proliferation. We set out to examine the underlying mechanism governing the increased susceptibility of cigarette smoke exposed ALI to SARS-CoV-2 infection. Single cell profiling of the cultures showed that infected airway cells displayed a global reduction in gene expression across all airway cell types. Interestingly, interferon response genes were induced in SARS-CoV-2 infected airway epithelial cells in the ALI cultures but smoking exposure together with SARS-CoV-2 infection reduced the interferon response. Treatment of cigarette smoke-exposed ALI cultures with Interferon {beta}-1 abrogated the viral infection, suggesting that the lack of interferon response in the cigarette smoke-exposed ALI cultures allows for more severe viral infection and cell death. In summary, our data show that acute smoke exposure allows for more severe proximal airway epithelial disease from SARS-CoV-2 by reducing the mucosal innate immune response and ABSC proliferation and has implications for disease spread and severity in people exposed to cigarette smoke.

cell biology↗

bioRxiv2020

SARS-CoV-2 infection of primary human lung epithelium for COVID-19 modeling and drug discovery

Coronavirus disease 2019 (COVID-19) is the latest respiratory pandemic resulting from zoonotic transmission of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). Severe symptoms include viral pneumonia secondary to infection and inflammation of the lower respiratory tract, in some cases causing death. We developed primary human lung epithelial infection models to understand responses of proximal and distal lung epithelium to SARS-CoV-2 infection. Differentiated air-liquid interface cultures of proximal airway epithelium and 3D organoid cultures of alveolar epithelium were readily infected by SARS-CoV-2 leading to an epithelial cell-autonomous proinflammatory response. We validated the efficacy of selected candidate COVID-19 drugs confirming that Remdesivir strongly suppressed viral infection/replication. We provide a relevant platform for studying COVID-19 pathobiology and for rapid drug screening against SARS-CoV-2 and future emergent respiratory pathogens. One Sentence SummaryA novel infection model of the adult human lung epithelium serves as a platform for COVID-19 studies and drug discovery.

cell biology↗

bioRxiv2020

Antiviral Drug Screen of Kinase inhibitors Identifies Cellular Signaling Pathways Critical for SARS-CoV-2 Replication

Emergence of a highly contagious novel coronavirus, SARS-CoV-2 that causes COVID-19, has precipitated the current global health crisis with over 479,000 deaths and more than 9.3 million confirmed cases. Currently, our knowledge of the mechanisms of COVID-19 disease pathogenesis is very limited which has hampered attempts to develop targeted antiviral strategies. Therefore, we urgently need an effective therapy for this unmet medical need. Viruses hijack and dysregulate cellular machineries in order for them to replicate and infect more cells. Thus, identifying and targeting dysregulated signaling pathways that have been taken over by viruses is one strategy for developing an effective antiviral therapy. We have developed a high-throughput drug screening system to identify potential antiviral drugs targeting SARS-CoV-2. We utilized a small molecule library of 430 protein kinase inhibitors, which are in various stages of clinical trials. Most of the tested kinase antagonists are ATP competitive inhibitors, a class of nucleoside analogs, which have been shown to have potent antiviral activity. From the primary screen, we have identified 34 compounds capable of inhibiting viral cytopathic effect in epithelial cells. Network of drug and protein relations showed that these compounds specifically targeted a limited number of cellular kinases. More importantly, we have identified mTOR-PI3K-AKT, ABL-BCR/MAPK, and DNA-Damage Response (DDR) pathways as key cellular signaling pathways critical for SARS-CoV-2 infection. Subsequently, a secondary screen confirmed compounds such as Berzosertib (VE-822), Vistusertib (AZD2014), and Nilotinib with anti SARS-CoV-2 activity. Finally, we found that Berzosertib, an ATR kinase inhibitor in the DDR pathway, demonstrated potent antiviral activity in a human epithelial cell line and human induced pluripotent stem cell (hIPSC)-derived cardiomyocytes. These inhibitors are already in clinical trials of phase 2 or 3 for cancer treatment, and can be repurposed as promising drug candidates for a host-directed therapy of SARS-CoV-2 infection. In conclusion, we have identified small molecule inhibitors exhibiting anti SARS-CoV-2 activity by blocking key cellular kinases, which gives insight on important mechanism of host-pathogen interaction. These compounds can be further evaluated for the treatment of COVID-19 patients following additional in vivo safety and efficacy studies. DisclosuresNone declared.

microbiology↗