Mark T. Heise
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View article: Infection Of Rhesus Macaques With O’nyong-nyong Virus UVIR-O804 Recapitulates Key Aspects of Human Clinical Disease
Infection Of Rhesus Macaques With O’nyong-nyong Virus UVIR-O804 Recapitulates Key Aspects of Human Clinical Disease Open
1. Abstract O’nyong-nyong virus (ONNV) is a mosquito-borne alphavirus first isolated in Uganda in 1959. Since its discovery, ONNV has caused several outbreaks in Africa, manifesting clinically as fever, rash, and joint/muscle pain lasting …
View article: Adaptive immune response to West Nile virus infection in the Collaborative Cross mouse model: A database of cellular phenotypes and Quantitative Trait Loci
Adaptive immune response to West Nile virus infection in the Collaborative Cross mouse model: A database of cellular phenotypes and Quantitative Trait Loci Open
West Nile virus (WNV) infection can lead to a wide range of clinical outcomes, from asymptomatic to self-limiting febrile and serious neuro-invasive disease. Knowledge of the genetic factors contributing to the heterogeneity of this diseas…
View article: Identification of spirodioxolane nsP2 helicase inhibitors with antialphaviral activity
Identification of spirodioxolane nsP2 helicase inhibitors with antialphaviral activity Open
Spirodioxolanes were identified as a new series of direct-acting nsP2 helicase inhibitors with activity against alphaviruses. Analogs such as 6b maintained activity against viral mutants with resistance to first-generation nsP2 helicase in…
View article: Neuroinvasive Flavivirus Pathogenesis Is Restricted by Host Genetic Factors in Collaborative Cross Mice, Independently of Oas1b
Neuroinvasive Flavivirus Pathogenesis Is Restricted by Host Genetic Factors in Collaborative Cross Mice, Independently of Oas1b Open
Powassan virus (POWV) is an emerging tick-borne flavivirus that causes neuroinvasive diseases, including encephalitis, meningitis, and paralysis. Similar to other neuroinvasive flaviviruses, such as West Nile virus (WNV) and Japanese encep…
View article: <i> <b>N</b> </i> -Alkyl Sulfamates as a New Class of nsP2 Cysteine Protease Inhibitors with Broad-Spectrum Antialphaviral Activity
<i> <b>N</b> </i> -Alkyl Sulfamates as a New Class of nsP2 Cysteine Protease Inhibitors with Broad-Spectrum Antialphaviral Activity Open
The emergence of mosquito-borne alphaviruses that cause chronic arthritis or encephalitis underscores the urgent need for broad-spectrum antiviral therapeutics. The viral nsP2 cysteine protease, which is essential for alphavirus replicatio…
View article: Insulin deficiency inhibits vaccine-mediated antibody and germinal center B-cell formation in mice
Insulin deficiency inhibits vaccine-mediated antibody and germinal center B-cell formation in mice Open
Individuals with diabetes are at increased risk for severe outcomes from vaccine-preventable infections and often mount weaker immune responses to vaccination. The diabetes-related factors underlying this impaired immunity remain unclear, …
View article: Identification of Spirodioxolane nsP2 Helicase Inhibitors with Antialphaviral Activity
Identification of Spirodioxolane nsP2 Helicase Inhibitors with Antialphaviral Activity Open
We describe the design, synthesis, and antialphaviral activity of spirodioxolane inhibitors targeting the alphavirus nsP2 helicase (nsP2hel). The spirodioxolanes are a new series of direct-acting antivirals that retain key molecular featur…
View article: Structure-Guided Design of Potent and Selective Covalent Inhibitors of SARS-CoV-1 and SARS-CoV-2 Papain-like Proteases with Antiviral Activity.
Structure-Guided Design of Potent and Selective Covalent Inhibitors of SARS-CoV-1 and SARS-CoV-2 Papain-like Proteases with Antiviral Activity. Open
The papain-like protease (PLpro), one of two essential cysteine proteases in human coronaviruses, is indispensable for viral polyprotein processing and immune evasion through deubiquitination and deIS-Gylation of host proteins. This dual r…
View article: Novel Computational Pipeline to Identify Target Sites for Broad Spectrum Antiviral Drugs
Novel Computational Pipeline to Identify Target Sites for Broad Spectrum Antiviral Drugs Open
Emerging viruses pose an ongoing threat to human health. While certain viral families are common sources of outbreaks, predicting the specific virus within a family that will cause the next outbreak or pandemic is not possible, creating an…
View article: The RNA helicase DDX39A binds a conserved structure in chikungunya virus RNA to control infection
The RNA helicase DDX39A binds a conserved structure in chikungunya virus RNA to control infection Open
View article: The host response to influenza infections in human lung and macrophages cell lines
The host response to influenza infections in human lung and macrophages cell lines Open
Objective The innate immune response of an infected host is an essential defense mechanism to fight influenza virus infections in the respiratory tract. This response is essential to limit virus replication and spread. However, an exacerba…
View article: Functional Roles for RNA Ribosylation in Mammalian Cells
Functional Roles for RNA Ribosylation in Mammalian Cells Open
In mammalian cells, the addition of ADP-ribose to proteins and DNA plays well established roles in regulating cell function. Recently, RNA ribosylation was also found in mammalian cells under conditions of cell stress, though the functiona…
View article: Enantioselective Chemical Probe for Chikungunya nsP2 Helicase with Antialphaviral Activity
Enantioselective Chemical Probe for Chikungunya nsP2 Helicase with Antialphaviral Activity Open
Chikungunya virus (CHIKV) replication relies on the multifunctional nsP2 protein, making it an attractive target for antiviral drug discovery. Here, we report the resolution of oxaspiropiperidine 1, a first-in-class inhibitor of the…
View article: Identification of Direct-Acting nsP2 Helicase Inhibitors with Antialphaviral Activity
Identification of Direct-Acting nsP2 Helicase Inhibitors with Antialphaviral Activity Open
Alphaviruses are mosquito-borne RNA viruses that pose a significant public health threat, with no FDA-approved antiviral therapeutics available. The nonstructural protein 2 helicase (nsP2hel) is an enzyme involved in unwinding dsRNA essent…
View article: The host response to influenza infections in human lung and macrophages cell lines
The host response to influenza infections in human lung and macrophages cell lines Open
Objective The innate immune response of an infected host is an essential defense mechanism to fight influenza virus infections in the respiratory tract. This response is essential to limit virus replication and spread. However, an exacerba…
View article: <i>N</i>-Alkyl Sulfamates as a New Class of nsP2 Cysteine Protease Inhibitors with Broad Spectrum Antialphaviral Activity
<i>N</i>-Alkyl Sulfamates as a New Class of nsP2 Cysteine Protease Inhibitors with Broad Spectrum Antialphaviral Activity Open
The emergence of mosquito-borne alphaviruses that cause chronic arthritis or encephalitis underscores the urgent need for broad-spectrum antiviral therapeutics. The viral nsP2 cysteine protease, which is essential for alphavirus replicatio…
View article: A covalent chemical probe for Chikungunya nsP2 cysteine protease with antialphaviral activity and proteome-wide selectivity
A covalent chemical probe for Chikungunya nsP2 cysteine protease with antialphaviral activity and proteome-wide selectivity Open
View article: Highly dampened blood transcriptome response in HIV patients after respiratory infection
Highly dampened blood transcriptome response in HIV patients after respiratory infection Open
View article: Author Correction: Highly dampened blood transcriptome response in HIV patients after respiratory infection
Author Correction: Highly dampened blood transcriptome response in HIV patients after respiratory infection Open
View article: Identification of a Broadly Acting Inhibitor of the Alphavirus Non-Structural Protein 2 Helicase
Identification of a Broadly Acting Inhibitor of the Alphavirus Non-Structural Protein 2 Helicase Open
Alphaviruses are mosquito-borne viruses that have caused significant outbreaks in the 21 st century. Despite multiple recent outbreaks, there are no approved antiviral drugs to treat any alphavirus infection. Therefore, developing broadly …
View article: Species-Dependent Metabolism of a Covalent nsP2 Protease Inhibitor with In Vivo Antialphaviral Activity
Species-Dependent Metabolism of a Covalent nsP2 Protease Inhibitor with In Vivo Antialphaviral Activity Open
RA-0002034 (1) is a potent covalent inhibitor targeting the nsP2 cysteine protease. The species-dependent pharmacokinetics and metabolism of 1 were investigated to evaluate its therapeutic potential. Pharmacokinetic profiling…
View article: Chikungunya virus-specific CD4+ T cells are associated with chronic chikungunya viral arthritic disease in humans
Chikungunya virus-specific CD4+ T cells are associated with chronic chikungunya viral arthritic disease in humans Open
Chikungunya virus (CHIKV) is a mosquito-borne virus that can cause chronic chikungunya virus disease (CHIKVD), which is characterized by persistent incapacitating arthralgia. Despite recurring CHIKV outbreaks and recent approval of a vacci…
View article: An Enantioselective Chemical Probe for Chikungunya nsP2 Helicase with Antialphaviral Activity
An Enantioselective Chemical Probe for Chikungunya nsP2 Helicase with Antialphaviral Activity Open
Chikungunya virus (CHIKV) replication relies on the multifunctional nsP2 protein, making it an attractive target for antiviral drug discovery. Here, we report the resolution of oxaspiropiperidine 1 , a first-in-class inhibitor of the CHIKV…
View article: Development of a virulent O'nyong'nyong challenge model to determine heterologous protection mediated by a hydrogen peroxide-inactivated chikungunya virus vaccine.
Development of a virulent O'nyong'nyong challenge model to determine heterologous protection mediated by a hydrogen peroxide-inactivated chikungunya virus vaccine. Open
O'nyong-nyong virus (ONNV) is a mosquito-transmitted alphavirus identified in Uganda in 1959. The virus has potential for enzootic and urban transmission cycles, and in humans, ONNV infection manifests as fever, rash, and joint/muscle pain…
View article: Core mitochondrial genes are down-regulated during SARS-CoV-2 infection of rodent and human hosts
Core mitochondrial genes are down-regulated during SARS-CoV-2 infection of rodent and human hosts Open
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins bind to host mitochondrial proteins, likely inhibiting oxidative phosphorylation (OXPHOS) and stimulating glycolysis. We analyzed mitochondrial gene expression in …
View article: Identification of Direct-acting nsP2 Helicase Inhibitors with Antialphaviral Activity
Identification of Direct-acting nsP2 Helicase Inhibitors with Antialphaviral Activity Open
Alphaviruses are mosquito-borne RNA viruses that pose a significant public health threat, with no FDA-approved antiviral therapeutics available. The non-structural protein 2 helicase (nsP2hel) is an enzyme involved in unwinding dsRNA essen…
View article: A covalent chemical probe for Chikungunya nsP2 cysteine protease with antialphaviral activity and proteome-wide selectivity
A covalent chemical probe for Chikungunya nsP2 cysteine protease with antialphaviral activity and proteome-wide selectivity Open
View article: Species Dependent Metabolism of a Covalent nsP2 Protease Inhibitor with <i>in Vivo</i> Anti-alphaviral Activity
Species Dependent Metabolism of a Covalent nsP2 Protease Inhibitor with <i>in Vivo</i> Anti-alphaviral Activity Open
RA-0002034 ( 1 ) is a potent covalent inhibitor targeting the alphavirus nsP2 cysteine protease. The species-dependent pharmacokinetics and metabolism of 1 were investigated to evaluate its therapeutic potential. Pharmacokinetic profiling …
View article: Analysis of blood proteome in influenza-infected patients reveals new insights into the host response signatures distinguishing mild severe infections
Analysis of blood proteome in influenza-infected patients reveals new insights into the host response signatures distinguishing mild severe infections Open
IntroductionInfluenza infections result in a wide spectrum of disease outcomes, ranging from asymptomatic cases to fatal illness. While immunopathology contributes to an increased risk of hospitalization, the host factors that drive predis…
View article: Lethal COVID-19 associates with RAAS-induced inflammation for multiple organ damage including mediastinal lymph nodes.
Lethal COVID-19 associates with RAAS-induced inflammation for multiple organ damage including mediastinal lymph nodes. Open
Lethal COVID-19 outcomes are attributed to classic cytokine storm. We revisit this using RNA sequencing of nasopharyngeal and 40 autopsy samples from patients dying of SARS-CoV-2. Subsets of the 100 top-upregulated genes in nasal swabs are…