Alfavirusna kimerična cjepiva protiv alfavirusnih uzročnika encefalitisa

Encephalitic viruses in the Family Togaviridae, genus Alphavirus are zoonotic pathogens that are transmitted via hematophagous arthropods and have a widespread distribution in North, Central and South America and include Venezuelan equine encephalitis virus (VEEV), Western equine encephalitis virus (WEEV), Eastern equine encephalitis virus (EEEV). The deficit in specific antiviral drugs or vaccines for effective treatment or prevention of infection and disease in humans has prompted the development of recombinant live attenuated vaccines utilizing Sindbis virus (SIN), a relatively nonpathogenic alphavirus in humans, as a means for expression all of the structural proteins of the virulent alphaviruses. The safety and efficacy of these chimeric SIN/VEE viruses have been extensively evaluated in animal models, including immunodeficient mice. The epidemiological distribution of these viruses and the disease manifestations are reviewed briefly. Progress in the evaluation of the safety, immunogenicity and efficacy of the SIN/VEEV and SIN/EEEV candidate vaccines against VEEV and EEEV, respectively, as well as chimeric SIN/RVFV vaccine candidates and the potential for elucidation of the mechanism of efficacy employing mice with selective immunodeficiencies is discussed.Virusi encefalitisa iz porodice Togaviridae, roda Alphavirus su zoonozni uzročnicikoje prenose hematofagni člankonošci rasprostranjeni u Sjevernoj, Centralnoj i Južnoj Americi te uključuju virus venezuelskog konjskog encefalitisa (engl. Venezuelan equine encephalitis virus, VEEV), virus zapadnog konjskog encefalitisa (engl. Western equine encephalitis virus, WEEV) i virus istočnog konjskog encefalitisa (engl. Eastern equine encephalitis virus, EEEV). Manjak specifičnih antivirusnih lijekova ili cjepiva za učinkovito liječenje ili sprječavanje infekcija i bolesti u ljudi potaklo je razvoj rekombiniranih živih atenuiranih cjepiva koja sadrže Sindbis virus (SIN), relativno bezopasan alfavirus za ljude, kao ekspresijski vektor svih strukturalnih proteina virulentnih alfavirusa. Sigurnost i učinkovitost ovih kimeričnih SIN/VEE virusa opsežno je proučavana na životinjskim modelima, uključujući imunodeficijentne miševe. Epidemiološka rasprostranjenost ovih virusa i manifestacije bolesti ukratko su opisane. Raspravlja se o postignutom napretku u ocjenjivanju sigurnosti, imunogeničnosti i učinkovitosti SIN/VEEV i SIN/EEEV potencijalnih cjepiva protiv VEEV odnosno EEEV, kao i potencijalnih kimeričnih SIN/RVFV cjepiva te moguće razjašnjenje mehanizma djelotvornosti koristeći miševe selektivne imunodeficijentnosti

Use of the informational spectrum methodology for rapid biological analysis of the novel coronavirus 2019-nCoV: prediction of potential receptor, natural reservoir, tropism and therapeutic/vaccine target [version 1; peer review: awaiting peer review]

A novel coronavirus recently identified in Wuhan, China (2019-nCoV) has expanded the number of highly pathogenic coronaviruses affecting humans. The 2019-nCoV represents a potential epidemic or pandemic threat, which requires a quick response for preparedness against this infection. The present report uses the informational spectrum methodology to identify the possible origin and natural host of the new virus, as well as putative therapeutic and vaccine targets. The performed in silico analysis indicates that the newly emerging 2019-nCoV is closely related to severe acute respiratory syndrome (SARS)-CoV and, to a lesser degree, Middle East respiratory syndrome (MERS)-CoV. Moreover, the well-known SARS-CoV receptor (ACE2) might be a putative receptor for the novel virus as well. Additional results indicated that civets and poultry are potential candidates for the natural reservoir of the 2019-nCoV, and that domain 288-330 of S1 protein from the 2019-nCoV represents promising therapeutic and/or vaccine target.info:eu-repo/semantics/publishedVersio

Review of Mammarenavirus Biology and Replication

The family Arenaviridae is divided into three genera: Mammarenavirus, Reptarenavirus, and Hartmanivirus. The Mammarenaviruses contain viruses responsible for causing human hemorrhagic fever diseases including New World viruses Junin, Machupo, Guanarito, Sabia, and Chapare virus and Old World viruses Lassa, and Lujo virus. These two groups of arenaviruses share the same genome organization composed of two ambisense RNA segments. These segments contain four open reading frames that encode for four proteins: the nucleoprotein, glycoprotein precursor, L protein, and Z. Despite their genome similarities, these groups exhibit marked differences in their replication life cycles. This includes differences in attachment, entry, and immune evasion. By understanding the intricacy of replication in each of these viral species we can work to develop counter measures against human diseases. This includes the development of vaccines and antivirals for these emerging viral threats. Currently only the vaccine against Junin virus, Candid#1, is in use as well as Ribavirin for treatment of Lassa Fever. In addition, small molecule inhibitors can be developed to target various aspects of the virus life cycle. In these ways an understanding of the arenavirus replication cycle can be used to alleviate the mortality and morbidity of these infections worldwide

Simple Theoretical Criterion for Selection of Natural Compounds with Anti-COVID-19 Activity

A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the leading threat to global health. An effective antiviral could not only help those still vulnerable to the virus but could be a critical treatment if a virus emerges toward evading coronavirus disease 2019 (COVID-19) vaccines. Despite the significant efforts to test already-approved drugs for their potential to kill the virus, researchers found very few actually worked. Methods: The present report uses the electronic molecular descriptors, the quasi-valence number (AQVN), and the electron-ion interaction potential (EIIP), for the analysis of natural compounds with proven therapeutic activity against the COVID-19. Results: Based on the analysis of the electronic properties of natural compounds which are effective against SARS-CoV-2 virus the simple theoretical criterion for the selection of candidate compounds for the treatment of COVID-19 is proposed. Conclusions: The proposed theoretical criterion can be used for the identification and optimization of new lead compounds for the treatment of the COVID-19 disease and for the selection of the food and food supplements which could have a beneficial effect on COVID-19 patients

Visualization of Double-Stranded RNA Colocalizing With Pattern Recognition Receptors in Arenavirus Infected Cells

An important step in the initiation of the innate immune response to virus infection is the recognition of non-self, viral RNA, including double-stranded RNA (dsRNA), by cytoplasmic pattern recognition receptors (PRRs). For many positive-sense RNA viruses and DNA viruses, the production of viral dsRNA, and the interaction of viral dsRNA and PRRs are well characterized. However, for negative-sense RNA viruses, viral dsRNA was thought to be produced at low to undetectable levels and PRR recognition of viral dsRNA is still largely unclear. In the case of arenaviruses, the nucleocaspid protein (NP) has been identified to contain an exoribonuclease activity that preferentially degrades dsRNA in biochemical studies. Nevertheless, pathogenic New World (NW) arenavirus infections readily induce an interferon (IFN) response in a RIG-I dependent manner, and also activate the dsRNA-dependent Protein Kinase R (PKR). To better understand the innate immune response to pathogenic arenavirus infection, we used a newly identified dsRNA-specific antibody that efficiently detects viral dsRNA in negative-sense RNA virus infected cells. dsRNA was detected in NW arenavirus infected cells colocalizing with virus NP in immunofluorescence assay. Importantly, the dsRNA signals also colocalized with cytoplasmic PRRs, namely, PKR, RIG-I and MDA-5, as well as with the phosphorylated, activated form of PKR in infected cells. Our data clearly demonstrate the PRR recognition of dsRNA and their activation in NW arenavirus infected cells. These findings provide new insights into the interaction between NW arenaviruses and the host innate immune response

Drug Repurposing for Candidate SARS-CoV-2 Main Protease Inhibitors by a Novel in Silico Method

The SARS-CoV-2 outbreak caused an unprecedented global public health threat, having a high transmission rate with currently no drugs or vaccines approved. An alternative powerful additional approach to counteract COVID-19 is in silico drug repurposing. The SARS-CoV-2 main protease is essential for viral replication and an attractive drug target. In this study, we used the virtual screening protocol with both long-range and short-range interactions to select candidate SARS-CoV-2 main protease inhibitors. First, the Informational spectrum method applied for small molecules was used for searching the Drugbank database and further followed by molecular docking. After in silico screening of drug space, we identified 57 drugs as potential SARS-CoV-2 main protease inhibitors that we propose for further experimental testing. © 2020 by the authors

Could Inelastic Interactions Induce Quantum Probabilistic Transitions?

What are quantum entities? Is the quantum domain deterministic or probabilistic? Orthodox quantum theory (OQT) fails to answer these two fundamental questions. As a result of failing to answer the first question, OQT is very seriously defective: it is imprecise, ambiguous, ad hoc, non-explanatory, inapplicable to the early universe, inapplicable to the cosmos as a whole, and such that it is inherently incapable of being unified with general relativity. It is argued that probabilism provides a very natural solution to the quantum wave/particle dilemma and promises to lead to a fully micro-realistic, testable version of quantum theory that is free of the defects of OQT. It is suggested that inelastic interactions may induce quantum probabilistic transitions

Novel neurodigital interface reduces motion sickness in virtual reality

Virtual reality (VR) is a computer-created 3D environment with a focus on realistic scenes and pictures created for entertainment, medical and/or educational and training purposes. One of the major side effects of VR immersion reported in the scientific literature, media and social media is Visually Induced Motion Sickness (VIMS), with clinical symptoms such as disorientation, nausea, and oculomotor discomfort. VIMS is mostly caused by the discrepancy between the visual and vestibular systems and can lead to dizziness, nausea, and disorientation. In this study, we present one potential novel solution to combat motion sickness in VR, showcasing a significant reduction of nausea in VR users employing the META Quest 2 headsets in conjunction with a whole-body controller. Using a neurodigital approach, we facilitate a more immersive and comfortable VR experience. Our findings indicate a marked reduction in VR-induced nausea, paving the way to promote VR technology for broader applications across various fields

Lassa virus diversity and feasibility for universal prophylactic vaccine [version 1; referees: 3 approved]

Lassa virus (LASV) is a highly prevalent mammarenavirus in West Africa and is maintained in nature in a persistently infected rodent host, Mastomys natalensis, which is widely spread in sub-Saharan Africa. LASV infection of humans can cause Lassa fever (LF), a disease associated with high morbidity and significant mortality. Recent evidence indicates an LASV expansion outside its traditional endemic areas. In 2017, the World Health Organization (WHO) included LASV in top-priority pathogens and released a Target Product Profile (TPP) for vaccine development. Likewise, in 2018, the US Food and Drug Administration added LF to a priority review voucher program to encourage the development of preventive and therapeutics measures. In this article, we review recent progress in LASV vaccine research and development with a focus on the impact of LASV genetic and biological diversity on the design and development of vaccine candidates meeting the WHO’s TPP for an LASV vaccine