The novel coronavirus disease (COVID-19) pandemic remains a global public health crisis, presenting a broad range of challenges. To help address some of the main problems, the scientific community ...has designed vaccines, diagnostic tools and therapeutics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The rapid pace of technology development, especially with regard to vaccines, represents a stunning and historic scientific achievement. Nevertheless, many challenges remain to be overcome, such as improving vaccine and drug treatment efficacies for emergent mutant strains of SARS-CoV-2. Outbreaks of more infectious variants continue to diminish the utility of available vaccines and drugs. Thus, the effectiveness of vaccines and drugs against the most current variants is a primary consideration in the continual analyses of clinical data that supports updated regulatory decisions. The first two vaccines granted Emergency Use Authorizations (EUAs), BNT162b2 and mRNA-1273, still show more than 60% protection efficacy against the most widespread current SARS-CoV-2 variant, Omicron. This variant carries more than 30 mutations in the spike protein, which has largely abrogated the neutralizing effects of therapeutic antibodies. Fortunately, some neutralizing antibodies and antiviral COVID-19 drugs treatments have shown continued clinical benefits. In this review, we provide a framework for understanding the ongoing development efforts for different types of vaccines and therapeutics, including small molecule and antibody drugs. The ripple effects of newly emergent variants, including updates to vaccines and drug repurposing efforts, are summarized. In addition, we summarize the clinical trials supporting the development and distribution of vaccines, small molecule drugs, and therapeutic antibodies with broad-spectrum activity against SARS-CoV-2 strains.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
mRNA-based drugs have tremendous potential as clinical treatments, however, a major challenge in realizing this drug class will promise to develop methods for safely delivering the bioactive agents ...with high efficiency and without activating the immune system. With regard to mRNA vaccines, researchers have modified the mRNA structure to enhance its stability and promote systemic tolerance of antigenic presentation in non-inflammatory contexts. Still, delivery of naked modified mRNAs is inefficient and results in low levels of antigen protein production. As such, lipid nanoparticles have been utilized to improve delivery and protect the mRNA cargo from extracellular degradation. This advance was a major milestone in the development of mRNA vaccines and dispelled skepticism about the potential of this technology to yield clinically approved medicines. Following the resounding success of mRNA vaccines for COVID-19, many other mRNA-based drugs have been proposed for the treatment of a variety of diseases. This review begins with a discussion of mRNA modifications and delivery vehicles, as well as the factors that influence administration routes. Then, we summarize the potential applications of mRNA-based drugs and discuss further key points pertaining to preclinical and clinical development of mRNA drugs targeting a wide range of diseases. Finally, we discuss the latest market trends and future applications of mRNA-based drugs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Since the pandemic of COVID-19 has intensely struck human society, small animal model for this infectious disease is in urgent need for basic and pharmaceutical research. Although several COVID-19 ...animal models have been identified, many of them show either minimal or inadequate pathophysiology after SARS-CoV-2 challenge. Here, we describe a new and versatile strategy to rapidly establish a mouse model for emerging infectious diseases in one month by multi-route, multi-serotype transduction with recombinant adeno-associated virus (AAV) vectors expressing viral receptor. In this study, the proposed approach enables profound and enduring systemic expression of SARS-CoV-2-receptor hACE2 in wild-type mice and renders them vulnerable to SARS-CoV-2 infection. Upon virus challenge, generated AAV/hACE2 mice showed pathophysiology closely mimicking the patients with severe COVID-19. The efficacy of a novel therapeutic antibody cocktail RBD-chAbs for COVID-19 was tested and confirmed by using this AAV/hACE2 mouse model, further demonstrating its successful application in drug development.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Dementia is a degenerative brain disease, which is associated with severe cognitive impairments, where angiotensin receptor blockers (e.g., telmisartan) shown to attenuate demented conditions. The ...objective of this study is to formulate and characterize telmisartan mucoadhesive nanoemulgel (TMNEG) for intranasal delivery. TMNEG was developed using Sefsol 218 and oleic acid (oilmix), Tween 20 (surfactant) and Transcutol P (co-surfactant), followed by incorporation of different concentrations of chitosan solution. The droplet-size, size-distribution, zeta potential, pH and viscositywere evaluated for the TMNEG formulations. Later, mucoadhesive property, in vitro release pattern along with the mechanism of release and ex vivo permeation through goat nasal mucosa of the TMNEGs were evaluated. Photon correlation spectroscopy and thermodynamic stability studies had shown that optimized TMNEG formulation had a nanometric droplet size and acceptable pH. Drug release studies revealed that overall release in optimized TMNEG (57.45 ± 5.90%) is lower than optimized telmisartan nanoemulsion (71.71 ± 5.32%) within the time frame of 12 h, showing a delayed-release contributed by the chitosan coating. The higher release rate was found in both low and medium molecular weight chitosan-coated nanoemulgel at a concentration of 0.5% and 1.0% as compared to TMNEGs with high molecular weight chitosan. The in vitro release kinetic profile followed first-order reaction and Higuchi model with non-Fickian diffusion. Coating of nanoemulsion droplets with chitosan had shown to improve the mucoadhesive property, which further improved the permeation through goat nasal mucosa. Taking into consideration of mucoadhesive characteristics, extended drug release and improved ex vivo permeation, the developed TMNEG provides a potential platform for the delivery of telmisartan via intranasal route.
Display omitted
Background With the continuous emergence of new SARS-CoV-2 variants that feature increased transmission and immune escape, there is an urgent demand for a better vaccine design that will provide ...broader neutralizing efficacy. Methods We report an mRNA-based vaccine using an engineered "hybrid" receptor binding domain (RBD) that contains all 16 point-mutations shown in the currently prevailing Omicron and Delta variants. Results A booster dose of hybrid vaccine in mice previously immunized with wild-type RBD vaccine induced high titers of broadly neutralizing antibodies against all tested SARS-CoV-2 variants of concern (VOCs). In naïve mice, hybrid vaccine generated strong Omicron-specific neutralizing antibodies as well as low but significant titers against other VOCs. Hybrid vaccine also elicited CD8+/IFN-gamma+ T cell responses against a conserved T cell epitope present in wild type and all VOCs. Conclusions These results demonstrate that inclusion of different antigenic mutations from various SARS-CoV-2 variants is a feasible approach to develop cross-protective vaccines. Keywords: Omicron vaccine, mRNA vaccine, SARS-CoV-2, COVID-19, Variants of concern, Hybrid vaccine, Booster dose, Next generation vaccine, Cross-protectivity
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Nalaganje filtrov
Noben zadetek ni izbran!
Prosimo, izberite zadetke, ki jih želite izvoziti.
Iskanje je bilo uspešno shranjeno.
Urejanje
Iskanja ni bilo mogoče shraniti.
Shranjena iskanja si lahko ogledate v seznamu Moja iskanja.
Spremembe v shranjenem iskanju so uspešno shranjene.
Shrani iskanje
Vnos na polico
Noben zadetek ni izbran!
Dodajanje gradiva na polico je uspelo.
Dodajanje gradiva na polico je le deloma uspelo.
Dodajanje gradiva na polico je v celoti spodletelo.
Dodajanje gradiva na polico ni bilo potrebno.
Prosimo, izberite zadetke, ki jih želite dati na polico!
Na polico so bili uspešno dodani naslednji zapisi:
Na polico so bili uspešno dodani naslednji zapisi:
Vnosi, pri katerih je dodajanje na polico spodletelo:
Dodajanje na polico ni uspelo za vse izbrane vnose:
Vsa izbrana gradiva so že na polici.
Duplikat
Dosežena omejitev
Urejanje
Napaka
Urejanje
Dodajanje
Urejanje
Sprememba statusa
Opozorilo s to iskalno zahtevo že obstaja. Prosimo, preverite seznam Moja opozorila.
Imate že 10 aktivnih opozoril.
Pri urejanju opozorila ni bilo nobenih sprememb.
Pri dodajanju in/ali urejanju opozorila se je pojavila napaka. Prosimo, poskusite ponovno.
opac.user.alert.dialog.alert_success.info
Opozorilo je bilo uspešno dodano in aktivirano.
Spremembe v nastavitvah opozorila so uspešno shranjene.
PDF
