Florian Douam

• Ph.D.
• Professor (Assistant) at Boston University

Mice engrafted with components of a human immune system have become widely-used models for studying aspects of human immunity and disease. However, a defined methodology to objectively measure and compare the quality of the human immune response in different models is lacking. Here, by taking advantage of the highly immunogenic live-attenuated yell...

Positive-sense RNA viruses pose increasing health and economic concerns worldwide. Our limited understanding of how these viruses interact with their host and how these processes lead to virulence and disease seriously hampers the development of anti-viral strategies. Here, we demonstrate the tracking of (+) and (−) sense viral RNA at single-cell r...

Yellow fever virus (YFV) is an arthropod-borne flavivirus, infecting ~200,000 people worldwide annually and causing about 30,000 deaths. The live attenuated vaccine strain, YFV-17D, has significantly contributed in controlling the global burden of yellow fever worldwide. However, the viral and host contributions to YFV-17D attenuation remain elusiv...

Yellow fever (YF) was one of the most dangerous infectious diseases of the 18th and 19th centuries, resulting in mass casualties in Africa and the Americas. The etiologic agent is yellow fever virus (YFV), and its live-attenuated form, YFV-17D, remains one of the most potent vaccines ever developed. During the first half of the 20th century, vaccin...

Humanized mice, that is, animals engrafted with human tissues and/or expressing human genes, have been instrumental in improving our understanding of the pathogenesis and immunological processes that define some of the most challenging human-tropic viruses. In particular, mice engrafted with components of a human immune system (HIS) offer unprecede...

The effectiveness of multiple COVID-19 vaccinations in individuals with a history of SARS-CoV-2 infection remains unclear; specifically, elucidation of the durability of anti-viral antibody responses could provide important insights for epidemiological applications. We utilized the BU ELISA protocol to measure the circulating SARS-CoV-2 receptor-bi...

Tick-borne orthoflaviviruses (TBOVs) are a growing global health concern. Several representatives of this viral family cause fatal disease in humans with increasing case numbers throughout the last decades. The innate immune response, especially interferon (IFN)-dependent signaling, is an essential part of the human defense system that counteracts...

Nasal sprays for pre‐exposure prophylaxis against respiratory infections show limited protection (20–70%), largely due to their single mechanism of action—either neutralizing pathogens or blocking their entry at the nasal lining, and a failure to maximize the capture of respiratory droplets, allowing them to potentially rebound and reach deeper air...

The use of modified nucleotides to suppress the interferon response and maintain translation of self-amplifying RNA (saRNA), which has been achieved for mRNA, has not yet succeeded. We identify modified nucleotides that, when substituted at 100% in saRNA, confer innate immune evasion and robust long-term protein expression, and when formulated as a...

Advanced age is associated with an increased susceptibility to Coronavirus Disease (COVID)-19 and more severe outcomes, although the underlying mechanisms are understudied. The lung endothelium is located next to infected epithelial cells and bystander inflammation may contribute to thromboinflammation and COVID-19-associated coagulopathy. Here, we...

The recurring emergence of novel respiratory viruses has highlighted our poor understanding of the human immune mechanisms governing the resolution of lung infection in an immunologically naïve context. Using SARS-CoV-2 as a prototypical emerging respiratory virus, we leveraged mice co-engrafted with a genetically matched fetal lung xenograft (fLX)...

Interferons (IFNs) play crucial roles in antiviral defenses. Despite using the same Janus-activated kinase (JAK)–signal transducer and activator of transcription (STAT) signaling cascade, type I and III IFN receptors differ in the magnitude and dynamics of their signaling in terms of STAT phosphorylation, gene transcription, and antiviral responses...

Self-amplifying RNA (saRNA) will revolutionize vaccines and in situ therapeutics by enabling protein expression for longer duration at lower doses. However, a major barrier to saRNA efficacy is the potent early interferon response triggered upon cellular entry, resulting in saRNA degradation and translational inhibition. Substitution of mRNA with m...

Chronic hepatitis B (CHB), caused by hepatitis B virus (HBV), remains a major medical problem. HBV has a high propensity for progressing to chronicity and can result in severe liver disease, including fibrosis, cirrhosis, and hepatocellular carcinoma. CHB patients frequently present with viral coinfection, including human immunodeficiency virus typ...

Chronic hepatitis B (CHB), caused by hepatitis B virus (HBV), remains a major medical problem. HBV has a high propensity for progressing to chronicity and can result in severe liver disease, including fibrosis, cirrhosis and hepatocellular carcinoma. CHB patients frequently present with viral coinfection, including HIV and hepatitis delta virus. Ab...

A simple and robust cell culture system is essential for generating authentic SARS-CoV-2 stocks for evaluation of viral pathogenicity, screening of antiviral compounds, and preparation of inactivated vaccines. Evidence suggests that Vero E6, a cell line commonly used in the field to grow SARS-CoV-2, does not support efficient propagation of new vir...

The SARS-CoV-2 Omicron variant is more immune-evasive and less virulent than other major viral variants recognized to date1-12. Omicron spike (S), with an unusually large number of mutations, is considered the major driver of these phenotypes. We generated chimeric recombinant SARS-CoV-2 encoding the S gene of Omicron (BA.1 lineage) in the backbone...

The recently identified, globally predominant SARS-CoV-2 Omicron variant (BA.1) is highly transmissible, even in fully vaccinated individuals, and causes attenuated disease compared with other major viral variants recognized to date 1–7 . The Omicron spike (S) protein, with an unusually large number of mutations, is considered the major driver of t...

The human immunological mechanisms defining the clinical outcome of SARS-CoV-2 infection remain elusive. This knowledge gap is mostly driven by the lack of appropriate experimental platforms recapitulating human immune responses in a controlled human lung environment. Here, we report a mouse model (i.e. HNFL mice) co-engrafted with human fetal lung...

SARS-CoV-2, the causative agent of pandemic COVID-19, is rapidly evolving to be more transmissible and to exhibit evasive immune properties, compromising neutralization by antibodies from vaccinated individuals or convalescent-phase sera. Recently, SARS-CoV-2 variants B.1.617.1 (Kappa), B.1.617.2 (Delta), and B.1.618 with mutations within the spike...

Animal models recapitulating COVID-19 are critical to enhance our understanding of SARS-CoV-2 pathogenesis. Intranasally inoculated transgenic mice expressing human angiotensin-converting enzyme 2 under the cytokeratin 18 promoter (K18-hACE2) represent a lethal model of SARS-CoV-2 infection. We evaluated the clinical and virological dynamics of SAR...

SARS-CoV-2 can infect multiple organs, including lung, intestine, kidney, heart, liver, and brain. The molecular details of how the virus navigates through diverse cellular environments and establishes replication are poorly defined. Here, we generated a panel of phenotypically diverse, SARS-CoV-2-infectible human cell lines representing different...

Several animal models have been developed to study the pathophysiology of SARS-CoV-2 infection and to evaluate vaccines and therapeutic agents for this emerging disease. Similar to infection with SARS-CoV-1, infection of Syrian hamsters with SARS-CoV-2 results in moderate respiratory disease involving the airways and lung parenchyma but does not le...

Coronavirus disease-2019 (COVID-19) provokes a hypercoagulable state with increased incidence of thromboembolism and mortality. Platelets are major effectors of thrombosis and hemostasis. Suitable animal models are needed to better understand COVID-19-associated coagulopathy (CAC) and underlying platelet phenotypes. Here, we assessed K18-hACE2 mice...

The majority of SARS-CoV-2 infections among healthy individuals result in asymptomatic to mild disease. However, the immunological mechanisms defining effective lung tissue protection from SARS-CoV-2 infection remain elusive. Unlike mice solely engrafted with human fetal lung xenograft (fLX), mice co-engrafted with fLX and a myeloid-enhanced human...

Many enveloped viruses induce multinucleated cells (syncytia), reflective of membrane fusion events caused by the same machinery that underlies viral entry. These syncytia are thought to facilitate replication and evasion of the host immune response. Here, we report that co-culture of human cells expressing the receptor ACE2 with cells expressing S...

Coronavirus interaction with its viral receptor is a primary genetic determinant of host range and tissue tropism. SARS-CoV-2 utilizes ACE2 as the receptor to enter host cell in a species-specific manner. We and others have previously shown that ACE2 orthologs from New World monkey, koala and mouse cannot interact with SARS-CoV-2 to mediate viral e...

The lack of coronavirus-specific antiviral drugs has instigated multiple drug repurposing studies to redirect previously approved medicines for the treatment of SARS-CoV-2, the coronavirus behind the ongoing COVID-19 pandemic. A recent, large-scale, retrospective clinical study showed that famotidine, when administered at a high dose to hospitalize...

Animal models recapitulating the distinctive features of severe COVID-19 are critical to enhance our understanding of SARS-CoV-2 pathogenesis. Transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) under the cytokeratin 18 promoter (K18-hACE2) represent a lethal model of SARS-CoV-2 infection. However, the cause(s) and mechanisms o...

Hepatitis E virus (HEV) causes 14 million infections and 60,000 deaths per year globally, with immunocompromised persons and pregnant women experiencing severe symptoms. Although ribavirin can be used to treat chronic hepatitis E, toxicity in pregnant patients and the emergence of resistant strains are major concerns. Therefore there is an imminent...

The human immunological mechanisms defining the clinical outcome of SARS-CoV-2 infection remain elusive. This knowledge gap is mostly driven by the lack of appropriate experimental platforms recapitulating human immune responses in a controlled human lung environment. Here, we report a mouse model (i.e., HNFL mice) co-engrafted with human fetal lun...

Many enveloped viruses induce multinucleated cells (syncytia), reflective of membrane fusion events caused by the same machinery that underlies viral entry. These syncytia are thought to facilitate replication and evasion of the host immune response. Here, we report that co-culture of human cells expressing the receptor ACE2 with cells expressing S...

SARS-CoV-2 can infect multiple organs, including lung, intestine, kidney, heart, liver, and brain. The molecular details of how the virus navigates through diverse cellular environments and establishes replication are poorly defined. Here, we performed global proteomic analysis of the virus-host interface in a newly established panel of phenotypica...

Coronavirus interaction with its viral receptor is a primary genetic determinant of host range and tissue tropism. SARS-CoV-2 utilizes ACE2 as the receptor to enter host cell in a species-specific manner. We and others have previously shown that ACE2 orthologs from New World monkey, koala and mouse cannot interact with SARS-CoV-2 to mediate viral e...

Flaviviruses are enveloped, arthropod-borne, positive-strand RNA viruses that cause significant human disease. While the basic mechanisms of flavivirus entry and fusion are understood, little is known about the postfusion events that precede RNA replication, such as nucleocapsid disassembly. We recently developed a sensitive, conditionally replicat...

The lack of coronavirus-specific antiviral drugs has instigated multiple drug repurposing studies to redirect previously approved medicines for the treatment of SARS-CoV-2, the coronavirus behind the ongoing COVID-19 pandemic. A recent, large-scale, retrospective clinical study showed that famotidine, when administered at a high dose to hospitalize...

While the basic mechanisms of flavivirus entry and fusion are understood, little is known about the postfusion events that precede RNA replication, such as nucleocapsid disassembly. We describe here a sensitive, conditionally replication-defective yellow fever virus (YFV) entry reporter, YFVΔSK/Nluc, to quantitively monitor the translation of incom...

Live-attenuated vaccines (LAV) represent one of the most important medical innovations in human history. In the past three centuries, LAV have saved hundreds of millions of lives, and will continue to do so for many decades to come. Interestingly, the most successful LAVs, such as the smallpox vaccine, the measles vaccine, and the yellow fever vacc...

While the basic mechanisms of flavivirus entry and fusion are understood, little is known about the post-fusion events that precede RNA replication, such as nucleocapsid disassembly. We describe here a sensitive, conditionally replication-defective yellow fever virus (YFV) entry reporter, YFVΔSK/Nluc, to quantitively monitor the translation of inco...

Significance To shed light on the host range of Zika virus (ZIKV), we surveyed the virus’ ability to infect cells of evolutionarily diverse species. ZIKV replicates efficiently in human, great ape, Old and New World monkey, but not rodent cells. These observations correlated with ZIKV’s ability to blunt the cGAS/STING signaling pathway in all prima...

Amino-acid coevolution can be referred to mutational compensatory patterns preserving the function of a protein. Viral envelope glycoproteins, which mediate entry of enveloped viruses into their host cells, are shaped by coevolution signals that confer to viruses the plasticity to evade neutralizing antibodies without altering viral entry mechanism...

Detailed analysis of genotype 2 HCV E1E2 clusters. (DOCX)

List of genotype 2 cluster blocks mapped on the E1E2 reference sequences (JFH-1; AB047639). For each block, the initial and final position of the block predicted by BIS and the name of the cluster it belongs to are given. Blocks from each cluster are numerated from 1 to x (Block N°) to easily identify their position on the E1E2 sequences in S7 Fig,...

Putative functions of genotype 2 E1E2 coevolution clusters. We aligned 30 E1E2 amino acid sequences of HCV genotype 2 (2a and 2b) and, using the BIS method, we identified 21 clusters (S6 Fig; S3, S7 Table). Genotype 2 clusters harboring blocks that mapped residues previously reported in the literature to have a specific function are classified. The...

Detailed analysis of genotype 1a HCV E1E2 clusters. (DOCX)

Clusters of coevolving residues identified by BIS in DENV envelope glycoprotein E sequences of serotype 2. Clusters are computed with the BIS coevolution analysis method [22–24] and they correspond to maximum scores (symmetricity and environmental scores are set to 1, and the number of admissible exceptions to 0 or 1). For each cluster, the positio...

Putative functions of genotype 1a E1E2 coevolution clusters. We aligned 25 E1E2 amino acids sequences of HCV genotype 1a and identified using BIS method 16 clusters (S3 Fig; S4 Table). Genotype 1a clusters harboring blocks that mapped residues previously reported in the literature to have a specific function (S4 Fig) are classified. The known role(...

BIS methodology for coevolution analysis. Coevolution analyses require the identification of sequence variability and they are usually realized on families of homologous protein sequences, typically very divergent and represented by a large number of sequences. In contrast, studying viral sequences requires methods that can analyze serotypes and ge...

Clusters of coevolving residues identified by BIS in DENV envelope glycoprotein E and PrM sequences of serotype 2. 17 amino acids sequences of DENV E and PrM serotype 2 were aligned and 14 Clusters were identified by BIS. Clusters are computed with the BIS coevolution analysis method [22–24] and they correspond to maximum scores (symmetricity and e...

Mapping of genotype 1a cluster blocks on E1E2 reference sequences of genotype 1a (H77; AF009606) and genotype 2a (JFH-1; AB047639). Genotype 1a cluster blocks are represented as red horizontal bars positioned above the E1 and E2 H77 or JFH-1 aligned sequences. Each horizontal bar is numerated as follow: “Cluster ID-Block N°”. Respective positions o...

Genotype 2 HCV E1E2 coevolution networks. The 21 gt2 clusters (illustrated by distinct colors) are displayed within “strips” representing the E1E2 sequence. For each cluster, positions of the coevolving blocks in the E1E2 sequence are indicated within the corresponding “strip” (see S7 Table for cluster positions). On the top of each coevolving bloc...

BIS coevolution analysis of HCV E1E2 sequences. Ten groups of sequences were assembled and analyzed independently with the BIS method. Groups were constituted of E1E2 sequences from HCV types and sub-types from genotype 1a to 6a. Groups of sequences from genotypes 1 and 2 were constituted by pools of sequences from subtypes 1a and 1b (50 sequences)...

Clusters of coevolving residues identified by BIS in HCV E1E2 sequences of genotype 1a. Clusters are computed with the BIS analysis method similarly to S1 Table. Note that residue positions displayed in this table are specific to the set of patient sequences analyzed. Hence, nucleotide gaps generated during the analysis of the patient sequences by...

List of Genotype 1a cluster blocks mapped on E1E2 references sequences (H77, AF009606). For each block, the initial and final position of the block predicted by BIS and the name of the cluster it belongs to are given. Blocks from each cluster are numerated from 1 to x (Block N°) to easily identify their position on the E1E2 sequences in S4 Fig, whe...

Clusters of coevolving residues identified by BIS in HCV E1E2 sequences of genotype 2. Clusters are computed with the BIS analysis method similarly to S1 Table. Note that residue positions displayed in this table are specific to the set of patient sequences analyzed. Hence, nucleotide gaps generated during the analysis of the patient sequences by B...

Structural mapping of DENV E clusters. Mapping of the DENV E clusters 3 to 12 (illustrated by distinct colors) on the E dimeric structure (PDB 1K4R). For each cluster, positions of the coevolving blocks in E sequence are displayed within “strips” located above each structure (See S2 Table for cluster positions). Each cluster is identified by a dist...

Mapping of genotype 2 cluster blocks on E1E2 reference sequences of genotype 1a (H77; AF009606) and genotype 2a (JFH-1; AB047639). Genotype 2 cluster blocks are represented as blue horizontal bars positioned above the E1 and E2 H77 or JFH-1 aligned sequences. Each horizontal bar is numerated as follow: “Cluster number-Block N°”. Respective position...

Structural analysis of genotype 3 clusters involving E1 and the BL. Genotype 3 cluster 4 (blue), cluster 8 (red) and cluster 9 (green) are plotted on a tridimensional view of the E2core structure (PDB 4MWF) and on a vertical linear representation of E1. Each cluster is composed of blocks harboring a similar color. The Stem region (Stem) is represen...

Biophysical properties and ELISA detection of soluble BLd-H77. (A) Amino acid sequence of the soluble BLd-H77. Dotted lines represent internal disulfide bridges that might be involved in the functional folding of the soluble BLd-H77. (B) Detection of BLd-H77 in reducing and non-reducing condition following SDS-Page electrophoresis and coomassie blu...

BLd-H77 transmembranous form inhibits HCV infection. (A) Cell surface staining of C46 and BLd-tm following transduction of Huh7.5. Expression of C46 and BLd-tm (white) was measured by flow cytometry using an anti-hinge human IgG2 antibody and compared to the level of expression within non-transduced Huh7.5 (Grey). (B) CD81, SR-BI, Claudin-1 and Occ...

Functional linkage of E1 and BL coevolving residues identified by BIS. (A) Protein sequence alignment of E1E2 J6 and 2b1. Level of conservation for each amino acid position is indicated. Position of the coevolving blocks that belong to gt2 fusion cluster 5 are indicated by red rectangles. Position of the interchanged amino acid regions between J6 a...

BIS analysis of the coevolution of the transmembranes of E1 and E2. List of clusters identified by BIS that connect the transmembrane of E1 and E2. Six clusters were identified across the two major HCV genotypes. Location of the transmembrane domains within E1 and E2 are indicated for each genotype and sub-types. Position of the coevolving blocks l...

Coevolution analysis of HCV E1E2 genotype 1a sequences. The 16 gt1a clusters (illustrated by distinct colors) are displayed within “strips” representing the E1E2 sequence. For each cluster, positions of the coevolving blocks in the E1E2 sequence are indicated within the corresponding “strip” (see S4 Table for cluster positions). On the top of each...

Structural analysis of genotype 1a HCV E1E2 clusters. HCV E1E2 gt1a multifunctional clusters 4 (blue) and 16 (orange) (A), structural clusters 11 (orange), 2 (green) and 6 (red) (B) and undefined role clusters 3 (pink), 9 (emerald green), 13 (brown), 14 (blue) and 15 (yellow) (C) are plotted on a vertical linear representation of E1 and on a tridim...

Structural analysis of the genotype 2 HCV E1E2 clusters. (A) Plot of the gt2 structural cluster 19 on a tridimensional view of the E2core structure (PDB 4MWF). Gt2 structural (B), multifunctional (C), structural and multifunction (D), fusion (E) and undefined (F) clusters were plotted both on a vertical linear representation of E1 and onto the E2 c...

Construction of E1-E2 genotype 1a chimera to challenge BIS predictions. Protein sequence alignment of E1E2 H77 and A40. Level of conservation for each amino acid position is indicated. Position of the E1 and E2 block of interest belonging to the gt1a cluster 5 are indicated by red asterisks. Position of the three H77 amino acid residues that will b...

BLd-H77 inhibits HCV infection. (A) Quantification of HCVcc infectious titers following dose-dependent neutralization of HCVcc H77/JFH-1 by BLd-H77. Four days following BLd-H77 dose-dependent neutralization of HCVcc H77/JFH-1 infection (see Fig 4F), Huh7.5 cell culture supernatants were harvested and used to infect naïve Huh7.5 cells. Four days pos...

Effect of BLd-H77 on E2 and HCV pseudoparticles binding. (A) BLd-H77 effect on E2 and HCVpp binding to Huh7.5 cells (Left). Huh7.5 cells, pre-incubated with PBS (top panels) or BLd-H77 (50μg/ml) (bottom panels), were mixed (white) or not (grey), at 37°C for 1h with soluble E2 or with concentrated H77-HCVpp. Bound soluble E2 or HCVpp were then stain...

Effect of BLd-H77 on cell-cell fusion. (A) LTRhiv-luciferase vector transduced 293T cells expressing H77 HCV (left panel) or VSV (right panel) envelope glycoproteins were co-cultured with Tat-expressing Huh7.5 cells. Co-culture were pre-incubated for 1h with 50μg/ml of BLd-H77 or PBS, washed and incubated for 3 min with a pH7 (red) or pH5 (orange)...

Supplementary Figures and Supplementary Tables

The past decade has seen tremendous progress in understanding hepatitis C virus (HCV) biology and its related disease, hepatitis C. Major advances in characterizing viral replication have led to the development of direct-acting anti-viral therapies that have considerably improved patient treatment outcome and can even cure chronic infection. Howeve...

Importance: Hepatitis C Virus (HCV) mainly replicates within the liver. However, it has been shown that patient-derived HCV particles can slightly infect lymphocytes in vitro and in vivo, highlighting the existence of lymphotropism determinants within HCV viral proteins. We isolated HCV envelope glycoproteins from patient B-lymphocytes that confer...

Infectious diseases are the second leading cause of death worldwide. Although the host multitropism of some pathogens has rendered their manipulation possible in animal models, the human-restricted tropism of numerous viruses, bacteria, fungi, and parasites has seriously hampered our understanding of these pathogens. Hence, uncovering the genetic b...

The development of lentiviral vectors for expression of a specific antibody can be achieved through the transduction of mature B cells. This approach would provide a versatile tool for active immunotherapy strategies for infectious diseases or cancer, as well as for protein engineering. Here, we created a lentiviral expression system mimicking the...

Unlabelled: In our study, we characterized the effect of monensin, an ionophore that is known to raise the intracellular pH, on the hepatitis C virus (HCV) life cycle. We showed that monensin inhibits HCV entry in a pangenotypic and dose-dependent manner. Monensin induces an alkalization of intracellular organelles, leading to an inhibition of the...

Hepatitis C virus (HCV) is a major cause of liver disease worldwide. Acute infection often progresses to chronicity resulting frequently in fibrosis, cirrhosis, and in rare cases, in the development of hepatocellular carcinoma (HCC). Although HCV has proven to be an arduous object of research and has raised important technical challenges, several e...

Hepatitis C virus (HCV) is an enveloped, positive strand RNA virus classified within the Flaviviridae family and is a major cause of liver disease worldwide. HCV life cycle and propagation are tightly linked to several aspects of lipid metabolism. HCV propagation depends on and also shapes several aspects of lipid metabolism such as cholesterol upt...

Hepatitis C virus (HCV) is a leading cause of cirrhosis and liver cancer worldwide. We recently characterized for the first time the expression of Signaling Lymphocyte Activating Molecule 3 (SLAMF3) in human hepatocytes and here, we report that SLAMF3 interacts with the HCV viral protein E2 and is implicated in HCV entry process. We found a strong...

Hepatitis C virus (HCV) establishes infection using host lipid metabolism pathways that are thus considered potential targets for indirect anti-HCV strategies. HCV enters the cell via clathrin-dependent endocytosis, interacting with several receptors, and virus-cell fusion, which depends on acidic pH and the integrity of cholesterol-rich domains of...

Unlabelled: Hepatitis C virus (HCV) envelope glycoproteins E1 and E2 are important mediators for productive cell entry. However, knowledge about their structure, intra- or intermolecular dialogs, and conformational changes is scarce, limiting the design of therapeutic strategies targeting E1E2. Here we sought to investigate how certain domains of...

Trends in conventional plant breeding and in biotechnology research are analyzed with a focus on production and productivity of individual organisms. Our growing understanding of the productive/adaptive potential of (crop) plants is a prerequisite to increasing this potential and also its expression under environmental constraints. This review conc...

Unlabelled: Hepatitis C virus (HCV) is a major cause of chronic liver disease. Despite recent success in improving anti-HCV therapy, additional progress is still needed to develop cheaper and interferon (IFN)-free treatments. Here, we report that ferroquine (FQ), an antimalarial ferrocenic analog of chloroquine, is a novel inhibitor of HCV. FQ pot...

The protonation of histidine in acidic environments underpins its role in regulating the function of pH-sensitive proteins. For pH-sensitive viral fusion proteins, histidine protonation in the endosome leads to the activation of their membrane fusion function. The HCV (hepatitis C virus) glycoprotein E1-E2 heterodimer mediates membrane fusion withi...