Structural Proteomics of Emerging Viruses: The Examples of SARS-CoV and Other Coronaviruses

: Viral interference, originally, referred to a state of temporary immunity, is a state whereby infection with a virus limits replication or production of a second infecting virus. However, replication of a second virus could also be dominant over the first virus. In fact, dominance can alternate between the two viruses. Expression of type I interferon genes is many times upregulated in infected epithelial cells. Since the interferon system can control most, if not all, virus infections in the absence of adaptive immunity, it was proposed that viral induction of a nonspecific localized temporary state of immunity may provide a strategy to control viral infections. Clinical observations also support such a theory, which gave credence to the development of superinfection therapy (SIT). SIT is an innovative therapeutic approach where a non-pathogenic virus is used to infect patients harboring a pathogenic virus. : For the functional cure of persistent viral infections and for the development of broad- spectrum antivirals against emerging viruses a paradigm shift was recently proposed. Instead of the virus, the therapy should be directed at the host. Such a host-directed-therapy (HDT) strategy could be the activation of endogenous innate immune response via toll-like receptors (TLRs). Superinfection therapy is such a host-directed-therapy, which has been validated in patients infected with two completely different viruses, the hepatitis B (DNA), and hepatitis C (RNA) viruses. SIT exerts post-infection interference via the constant presence of an attenuated non-pathogenic avian double- stranded (ds) RNA viral vector which boosts the endogenous innate (IFN) response. SIT could, therefore, be developed into a biological platform for a new “one drug, multiple bugs” broad-spectrum antiviral treatment approach.

Download Full-text

Bats Prove To Be Rich Reservoirs for Emerging Viruses

Microbe Magazine ◽

10.1128/microbe.3.521.1 ◽

2008 ◽

Vol 3 (11) ◽

pp. 521-528 ◽

Cited By ~ 1

Author(s):

Charles H. Calisher ◽

Kathryn V. Holmes ◽

Tony Schountz ◽

Samuel R. Dominguez ◽

Paul Cryan

Keyword(s):

Emerging Viruses

Download Full-text

Using focused structural proteomics to elucidate the molecular basis of MAPK regulation in T cells

Acta Crystallographica Section A Foundations of Crystallography ◽

10.1107/s010876730809538x ◽

2008 ◽

Vol 64 (a1) ◽

pp. C143-C144

Author(s):

R. Page ◽

D.A. Critton ◽

A. Tortajada ◽

B.L. Brown ◽

K. Betz

Keyword(s):

T Cells ◽

Molecular Basis ◽

Structural Proteomics

Download Full-text

491. Aerosol-Generating Medical Procedures: Transmission of SARS-CoV-2 and Emerging Viruses

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.684 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S312-S312

Author(s):

Seth D Judson ◽

Vincent J Munster

Keyword(s):

High Risk ◽

Severe Disease ◽

Experimental Studies ◽

Virus Transmission ◽

Nosocomial Transmission ◽

Medical Procedures ◽

Emerging Viruses ◽

Zoonotic Viruses ◽

Increased Risk ◽

Hospital Acquired

Abstract Background During the pandemic of coronavirus disease 2019 (COVID-19), many questions arose regarding risks for hospital-acquired or nosocomial transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Aerosol generating medical procedures (AGMPs), techniques that can generate infectious, virus-laden aerosols, could potentially amplify transmission among healthcare workers (HCWs). Thus, it was widely recommended that HCWs use airborne precautions when performing AGMPs. However, in clinical settings it is often unclear what procedures constitute AGMPs and how the risk varies by procedure or pathogen. We set out to further define AGMPs and assess the risk for nosocomial transmission of SARS-CoV-2 and other high-risk viruses via AGMPs. Methods We identified potential AGMPs and emerging viruses that were high-risk for nosocomial transmission through reviewing experimental and clinical data. Potential AGMPs were those associated with previous virus transmission or mechanically capable of transmission. High-risk viruses were defined as those that cause severe disease in humans for which limited therapies or interventions exist, are infectious via aerosols in humans or non-human primates (NHPs), found in the respiratory tract of infected humans or NHPs, and had previous evidence of nosocomial transmission. Results We identified multiple potential AGMPs, which could be divided into those that generate aerosols or induce a patient to form aerosols, as well as eight families of high-risk viruses. All of the viruses were emerging zoonotic RNA viruses. In the family Coronaviridae, we identified potential evidence for SARS-CoV-1, MERS-CoV, and SARS-CoV-2 transmission via AGMPs. SARS-CoV-1 and SARS-CoV-2 were also found to be similarly stable when aerosolized. Conclusion Multiple emerging zoonotic viruses pose a high risk for nosocomial transmission through a variety of AGMPs. Given the similar stability of SARS-CoV-2 with SARS-CoV-1 when aerosolized and prior nosocomial transmission of SARS-CoV-1 via AGMPs, we suspect that certain AGMPs pose an increased risk for SARS-CoV-2 transmission. Additional experimental studies and on-site clinical sampling during AGMPs are necessary to further risk stratify AGMPs. Disclosures All Authors: No reported disclosures

Download Full-text

Fludarabine Inhibits Infection of Zika Virus, SFTS Phlebovirus, and Enterovirus A71

Viruses ◽

10.3390/v13050774 ◽

2021 ◽

Vol 13 (5) ◽

pp. 774

Author(s):

Chengfeng Gao ◽

Chunxia Wen ◽

Zhifeng Li ◽

Shuhan Lin ◽

Shu Gao ◽

...

Keyword(s):

Broad Spectrum ◽

Zika Virus ◽

Therapeutic Agent ◽

Viral Infections ◽

Rna Virus ◽

Emerging Viruses ◽

Enterovirus A71 ◽

Ic50 Values ◽

High Doses ◽

Severe Fever

Viral infections are one of the leading causes in human mortality and disease. Broad-spectrum antiviral drugs are a powerful weapon against new and re-emerging viruses. However, viral resistance to existing broad-spectrum antivirals remains a challenge, which demands development of new broad-spectrum therapeutics. In this report, we showed that fludarabine, a fluorinated purine analogue, effectively inhibited infection of RNA viruses, including Zika virus, Severe fever with thrombocytopenia syndrome virus, and Enterovirus A71, with all IC50 values below 1 μM in Vero, BHK21, U251 MG, and HMC3 cells. We observed that fludarabine has shown cytotoxicity to these cells only at high doses indicating it could be safe for future clinical use if approved. In conclusion, this study suggests that fludarabine could be developed as a potential broad-spectrum anti-RNA virus therapeutic agent.

Download Full-text

Seewis hantavirus in common shrew (Sorex araneus) in Sweden

Virology Journal ◽

10.1186/s12985-020-01477-w ◽

2020 ◽

Vol 17 (1) ◽

Author(s):

Olivia Wesula Lwande ◽

Nahla Mohamed ◽

Göran Bucht ◽

Clas Ahlm ◽

Gert Olsson ◽

...

Keyword(s):

Common Shrew ◽

Hemorrhagic Fever ◽

Sorex Araneus ◽

Genome Segment ◽

Cytochrome C Oxidase I ◽

Emerging Viruses ◽

Molecular Method ◽

Typing Method ◽

Common Shrew Sorex Araneus ◽

Genetic Assay

Abstract Background Rodent borne hantaviruses are emerging viruses infecting humans through inhalation. They cause hemorrhagic fever with renal syndrome and hemorrhagic cardiopulmonary syndrome. Recently, hantaviruses have been detected in other small mammals such as Soricomorpha (shrews, moles) and Chiroptera (bats), suggested as reservoirs for potential pandemic viruses and to play a role in the evolution of hantaviruses. It is important to study the global virome in different reservoirs, therefore our aim was to investigate whether shrews in Sweden carried any hantaviruses. Moreover, to accurately determine the host species, we developed a molecular method for identification of shrews. Method Shrews (n = 198), caught during 1998 in Sweden, were screened with a pan-hantavirus PCR using primers from a conserved region of the large genome segment. In addition to morphological typing of shrews, we developed a molecular based typing method using sequencing of the mitochondrial cytochrome C oxidase I (COI) and cytochrome B (CytB) genes. PCR amplified hantavirus and shrew fragments were sequenced and phylogenetically analysed. Results Hantavirus RNA was detected in three shrews. Sequencing identified the virus as Seewis hantavirus (SWSV), most closely related to previous isolates from Finland and Russia. All three SWSV sequences were retrieved from common shrews (Sorex araneus) sampled in Västerbotten County, Sweden. The genetic assay for shrew identification was able to identify native Swedish shrew species, and the genetic typing of the Swedish common shrews revealed that they were most similar to common shrews from Russia. Conclusion We detected SWSV RNA in Swedish common shrew samples and developed a genetic assay for shrew identification based on the COI and CytB genes. This was the first report of presence of hantavirus in Swedish shrews.

Download Full-text

SARS-CoV-2 Cellular Infection and Therapeutic Opportunities: Lessons Learned from Ebola Virus

Membranes ◽

10.3390/membranes11010064 ◽

2021 ◽

Vol 11 (1) ◽

pp. 64

Author(s):

Jordana Muñoz-Basagoiti ◽

Daniel Perez-Zsolt ◽

Jorge Carrillo ◽

Julià Blanco ◽

Bonaventura Clotet ◽

...

Keyword(s):

Viral Entry ◽

Ebola Virus ◽

Lessons Learned ◽

Productive Infection ◽

Target Cells ◽

Emerging Viruses ◽

Highly Pathogenic ◽

Life Threatening ◽

Pathogenic Viruses ◽

Cellular Machinery

Viruses rely on the cellular machinery to replicate and propagate within newly infected individuals. Thus, viral entry into the host cell sets up the stage for productive infection and disease progression. Different viruses exploit distinct cellular receptors for viral entry; however, numerous viral internalization mechanisms are shared by very diverse viral families. Such is the case of Ebola virus (EBOV), which belongs to the filoviridae family, and the recently emerged coronavirus SARS-CoV-2. These two highly pathogenic viruses can exploit very similar endocytic routes to productively infect target cells. This convergence has sped up the experimental assessment of clinical therapies against SARS-CoV-2 previously found to be effective for EBOV, and facilitated their expedited clinical testing. Here we review how the viral entry processes and subsequent replication and egress strategies of EBOV and SARS-CoV-2 can overlap, and how our previous knowledge on antivirals, antibodies, and vaccines against EBOV has boosted the search for effective countermeasures against the new coronavirus. As preparedness is key to contain forthcoming pandemics, lessons learned over the years by combating life-threatening viruses should help us to quickly deploy effective tools against novel emerging viruses.

Download Full-text